Research & Scholarship

Current Research and Scholarly Interests

Laboratory and ambulatory recording of physiological, responses to stressors in anxious and phobic patients.


Journal Articles

  • Autonomic Arousal During Actigraphically Estimated Waking and Sleep in Male Veterans With PTSD JOURNAL OF TRAUMATIC STRESS Bertram, F., Jamison, A. L., Slightam, C., Kim, S., Roth, H. L., Roth, W. T. 2014; 27 (5): 610-617


    Physiological hyperarousal is manifested acutely by increased heart rate, decreased respiratory sinus arrhythmia, and increased skin conductance level and variability. Yet it is uncertain to what extent such activation occurs with the symptomatic hyperarousal of posttraumatic stress disorder (PTSD). We compared 56 male veterans with current PTSD to 54 males who never had PTSD. Subjects wore ambulatory devices that recorded electrocardiograms, finger skin conductance, and wrist movement while in their normal environments. Wrist movement was monitored to estimate sleep and waking periods. Heart rate, but not the other variables, was elevated in subjects with PTSD equally during waking and during actigraphic sleep (effect sizes, Cohen's d, ranged from 0.63 to 0.89). The length of the sleep periods and estimated sleep fragmentation did not differ between groups. Group heart rate differences could not be explained by differences in body activity, PTSD hyperarousal symptom scores, depression, physical fitness, or antidepressant use.

    View details for DOI 10.1002/jts.21947

    View details for Web of Science ID 000343928000014

    View details for PubMedID 25322890

  • Psychiatry on Trial The Norway 2011 Massacre JOURNAL OF NERVOUS AND MENTAL DISEASE Roth, W. T., Dager, S. R. 2014; 202 (3): 181-185


    On July 22, 2011, Anders Breivik, a Norwegian citizen, detonated a fertilizer bomb near government buildings in Oslo, killing eight people, and then proceeded to a nearby island where the Labor Party was holding a youth camp. There, he killed 69 people before being arrested. Just before these events, he posted a "compendium" on the Web explaining his actions and encouraging others to do likewise. Much of the ensuing media coverage and trial focused on whether he was sane and whether he had a psychiatric diagnosis. One team of court-appointed psychiatrists found him to be psychotic with a diagnosis of paranoid schizophrenia and legally insane. A second team found him neither psychotic nor schizophrenic and, thus, legally sane. Their contrary opinions were not reconciled by observing his behavior in court. We discuss why experienced psychiatrists reached such fundamentally opposing diagnostic conclusions about a "home-grown" terrorist holding extreme political views.

    View details for DOI 10.1097/NMD.0000000000000109

    View details for Web of Science ID 000333453300001

    View details for PubMedID 24566502

  • Experiential, autonomic, and respiratory correlates of CO2 reactivity in individuals with high and low anxiety sensitivity PSYCHIATRY RESEARCH Blechert, J., Wilhelm, F. H., Meuret, A. E., Wilhelm, E. M., Roth, W. T. 2013; 209 (3): 566-573


    Psychometric studies indicate that anxiety sensitivity (AS) is a risk factor for anxiety disorders such as panic disorder (PD). To better understand the psychophysiological basis of AS and its relation to clinical anxiety, we examined whether high-AS individuals show similarly elevated reactivity to inhalations of carbon dioxide (CO2) as previously reported for PD and social phobia in this task. Healthy individuals with high and low AS were exposed to eight standardized inhalations of 20% CO2-enriched air, preceded and followed by inhalations of room air. Anxiety and dyspnea, in addition to autonomic and respiratory responses were measured every 15 s. Throughout the task, high AS participants showed a respiratory pattern of faster, shallower breathing and reduced inhalation of CO2 indicative of anticipatory or contextual anxiety. In addition, they showed elevated dyspnea responses to the second set of air inhalations accompanied by elevated heart rate, which could be due to sensitization or conditioning. Respiratory abnormalities seem to be common to high AS individuals and PD patients when considering previous findings with this task. Similarly, sensitization or conditioning of anxious and dyspneic symptoms might be common to high AS and clinical anxiety. Respiratory conditionability deserves greater attention in anxiety disorder research.

    View details for DOI 10.1016/j.psychres.2013.02.010

    View details for Web of Science ID 000326766300050

    View details for PubMedID 23489596

  • Airway constriction in asthma during sustained emotional stimulation with films BIOLOGICAL PSYCHOLOGY Ritz, T., Rosenfield, D., Wilhelm, F. H., Roth, W. T. 2012; 91 (1): 8-16


    Individuals with asthma have been shown to respond to unpleasant stimuli with bronchoconstriction, but little is known about the time course of responding during sustained emotional stimulation and whether it varies with patients' experience.To examine the time course of oscillatory resistance (R(os)) during emotionally evocative films in 15 asthma patients and 14 healthy controls.Participants viewed unpleasant, surgery, and neutral films, each ranging 3-5min in duration. R(os) and the respiratory pattern (respiration rate, tidal volume, minute ventilation) were monitored continuously. Following each film, participants rated their affective response and symptoms. The time course of R(os) during films was explored using multilevel modeling.Compared to neutral film sequences, unpleasant films (including those with surgery scenes) elicited a uniform pattern of initial increases in R(os) with peaks within the first 1-2min, followed by a gradual decline. Increases were more pronounced in asthma and during surgery films. Including additional respiratory parameters as time-varying covariates did not affect the temporal course of R(os) change. The rate of decline in R(os) (after the initial increase) was less in participants who experienced greater arousal and in patients who reported more shortness of breath. Patients more susceptible to psychological triggers in daily life showed slower rates of decline in R(os).The temporal course of bronchoconstriction to unpleasant stimulation is highly uniform in asthma, with strong constriction in early stages of stimulation. More sustained constriction in emotion-induced asthma could be a risk factor for developing asthma exacerbation in daily life.

    View details for DOI 10.1016/j.biopsycho.2012.03.014

    View details for Web of Science ID 000307693100002

    View details for PubMedID 22490762

  • Opposing Breathing Therapies for Panic Disorder: A Randomized Controlled Trial of Lowering vs Raising End-Tidal PCO2 JOURNAL OF CLINICAL PSYCHIATRY Kim, S., Wollburg, E., Roth, W. T. 2012; 73 (7): 931-939


    Teaching anxious clients to stop hyperventilating is a popular therapeutic intervention for panic. However, evidence for the theory behind this approach is tenuous, and this theory is contradicted by an opposing theory of panic, the false-suffocation alarm theory, which can be interpreted to imply that the opposite would be helpful.To test these opposing approaches by investigating whether either, both, or neither of the 2 breathing therapies is effective in treating patients with panic disorder.We randomly assigned 74 consecutive patients with DSM-IV-diagnosed panic disorder (mean age at onset = 33.0 years) to 1 of 3 groups in the setting of an academic research clinic. One group was trained to raise its end-tidal P(CO₂) (partial pressure of carbon dioxide, mm Hg) to counteract hyperventilation by using feedback from a hand-held capnometer, a second group was trained to lower its end-tidal P(CO₂) in the same way, and a third group received 1 of these treatments after a delay (wait-list). We assessed patients physiologically and psychologically before treatment began and at 1 and 6 months after treatment. The study was conducted from September 2005 through November 2009.Using the Panic Disorder Severity Scale as a primary outcome measure, we found that both breathing training methods effectively reduced the severity of panic disorder 1 month after treatment and that treatment effects were maintained at 6-month follow-up (effect sizes at 1-month follow-up were 1.34 for the raise-CO(2) group and 1.53 for the lower-CO(2) group; P < .01). Physiologic measurements of respiration at follow-up showed that patients had learned to alter their P(CO₂) levels and respiration rates as they had been taught in therapy.Clinical improvement must have depended on elements common to both breathing therapies rather than on the effect of the therapies themselves on CO(2) levels. These elements may have been changed beliefs and expectancies, exposure to ominous bodily sensations, and attention to regular and slow identifier: NCT00183521.

    View details for DOI 10.4088/JCP.11m07068

    View details for Web of Science ID 000315000200004

    View details for PubMedID 22901344

  • Do Unexpected Panic Attacks Occur Spontaneously? BIOLOGICAL PSYCHIATRY Meuret, A. E., Rosenfield, D., Wilhelm, F. H., Zhou, E., Conrad, A., Ritz, T., Roth, W. T. 2011; 70 (10): 985-991


    Spontaneous or unexpected panic attacks, per definition, occur "out of the blue," in the absence of cues or triggers. Accordingly, physiological arousal or instability should occur at the onset of, or during, the attack, but not preceding it. To test this hypothesis, we examined if points of significant autonomic changes preceded the onset of spontaneous panic attacks.Forty-three panic disorder patients underwent repeated 24-hour ambulatory monitoring. Thirteen natural panic attacks were recorded during 1960 hours of monitoring. Minute-by-minute epochs beginning 60 minutes before and continuing to 10 minutes after the onset of individual attacks were examined for respiration, heart rate, and skin conductance level. Measures were controlled for physical activity and vocalization and compared with time matched control periods within the same person.Significant patterns of instability across a number of autonomic and respiratory variables were detected as early as 47 minutes before panic onset. The final minutes before onset were dominated by respiratory changes, with significant decreases in tidal volume followed by abrupt carbon dioxide partial pressure increases. Panic attack onset was characterized by heart rate and tidal volume increases and a drop in carbon dioxide partial pressure. Symptom report was consistent with these changes. Skin conductance levels were generally elevated in the hour before, and during, the attacks. Changes in the matched control periods were largely absent.Significant autonomic irregularities preceded the onset of attacks that were reported as abrupt and unexpected. The findings invite reconsideration of the current diagnostic distinction between uncued and cued panic attacks.

    View details for DOI 10.1016/j.biopsych.2011.05.027

    View details for Web of Science ID 000296493800013

    View details for PubMedID 21783179

  • An affective computing approach to physiological emotion specificity: Toward subject-independent and stimulus-independent classification of film-induced emotions PSYCHOPHYSIOLOGY Kolodyazhniy, V., Kreibig, S. D., Gross, J. J., Roth, W. T., Wilhelm, F. H. 2011; 48 (7): 908-922


    The hypothesis of physiological emotion specificity has been tested using pattern classification analysis (PCA). To address limitations of prior research using PCA, we studied effects of feature selection (sequential forward selection, sequential backward selection), classifier type (linear and quadratic discriminant analysis, neural networks, k-nearest neighbors method), and cross-validation method (subject- and stimulus-(in)dependence). Analyses were run on a data set of 34 participants watching two sets of three 10-min film clips (fearful, sad, neutral) while autonomic, respiratory, and facial muscle activity were assessed. Results demonstrate that the three states can be classified with high accuracy by most classifiers, with the sparsest model having only five features, even for the most difficult task of identifying the emotion of an unknown subject in an unknown situation (77.5%). Implications for choosing PCA parameters are discussed.

    View details for DOI 10.1111/j.1469-8986.2010.01170.x

    View details for Web of Science ID 000291255500004

    View details for PubMedID 21261632

  • Effects of Breathing Training on Voluntary Hypo- and Hyperventilation in Patients with Panic Disorder and Episodic Anxiety APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK Wollburg, E., Roth, W. T., Kim, S. 2011; 36 (2): 81-91


    Anxiety disorders are associated with respiratory abnormalities. Breathing training (BT) aimed at reversing these abnormalities may also alter the anxiogenic effects of biological challenges. Forty-five Panic Disorder (PD) patients, 39 Episodic Anxiety patients, and 20 non-anxious controls underwent voluntary hypoventilation and hyperventilation tests twice while psychophysiological measures were recorded. Patients were randomized to one of two BT therapies (Lowering vs. Raising pCO(2)) or to a waitlist. Before treatment panic patients had higher respiration rates and more tidal volume instability and sighing at rest than did non-anxious controls. After the Lowering therapy, patients had lower pCO(2) during testing. However, neither reactivity nor recovery to either test differed between patients and controls, or were affected by treatment. Although the two treatments had their intended opposite effects on baseline pCO(2), other physiological measures were not affected. We conclude that baseline respiratory abnormalities are somewhat specific to PD, but that previously reported greater reactivity and slower recovery to respiratory challenges may be absent.

    View details for DOI 10.1007/s10484-011-9150-5

    View details for Web of Science ID 000290026100003

    View details for PubMedID 21373936

  • Methodological considerations in ambulatory skin conductance monitoring INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Doberenz, S., Roth, W. T., Wollburg, E., Maslowski, N. I., Kim, S. 2011; 80 (2): 87-95


    Little is known how much skin conductance (SC) recordings from the fingers are affected by factors such as electrode site deterioration, ambient temperature (TMP), or physical activity (ACT), or by age, sex, race, or body mass index. We recorded SC, TMP, and ACT in 48 healthy control subjects for a 24-hour period, and calculated SC level (SCL), its standard deviation, the coefficient of SC variation, and frequency and amplitude of non-specific SC fluctuations. One method of assessing electrode site deterioration showed an average decline of 20%, while a second method found no significant change. All SC measures were higher during waking than sleep. Other factors influenced different measures in different ways. Thus, 24-hour SC recording outside the laboratory is feasible, but some measures need to be corrected for the influence of confounding variables.

    View details for DOI 10.1016/j.ijpsycho.2011.02.002

    View details for Web of Science ID 000290648300001

    View details for PubMedID 21320551

  • Affective modulation of the acoustic startle: Does sadness engage the defensive system? BIOLOGICAL PSYCHOLOGY Kreibig, S. D., Wilhelm, F. H., Roth, W. T., Gross, J. J. 2011; 87 (1): 161-163


    It has been suggested that high arousal negative affective states, but not low arousal negative affective states, potentiate the startle response. Because sadness has generally been studied as a low arousal emotion, it remains unclear whether high arousal sadness would produce startle potentiation to a similar degree as high arousal fear. To address this issue, 32 participants viewed two sets of 10-min film clips selected to induce two affective states of high subjective arousal (fear, sadness) and a neutral state of low subjective arousal, while the eyeblink startle response associated with brief noise bursts was assessed using orbicularis oculi EMG. Larger blink magnitude was found for fearful than for sad or neutral clips. Implications for conceptualizing sadness are discussed.

    View details for DOI 10.1016/j.biopsycho.2011.02.008

    View details for Web of Science ID 000290195100020

    View details for PubMedID 21352887

  • Airway response to emotion- and disease-specific films in asthma, blood phobia, and health PSYCHOPHYSIOLOGY Ritz, T., Wilhelm, F. H., Meuret, A. E., Gerlach, A. L., Roth, W. T. 2011; 48 (1): 121-135


    Earlier research found autonomic and airway reactivity in asthma patients when they were exposed to blood-injection-injury (BII) stimuli. We studied oscillatory resistance (R(os)) in asthma and BII phobia during emotional and disease-relevant films and examined whether muscle tension counteracts emotion-induced airway constriction. Fifteen asthma patients, 12 BII phobia patients, and 14 healthy controls viewed one set of negative, positive, neutral, BII-related, and asthma-related films with leg muscle tension and a second set without. R(os), ventilation, cardiovascular activity, and skin conductance were measured continuously. R(os) was higher during emotional compared to neutral films, particularly during BII material, and responses increased from healthy over asthmatic to BII phobia participants. Leg muscle tension did not abolish R(os) increases. Thus, the airways are particularly responsive to BII-relevant stimuli, which could become risk factors for asthma patients.

    View details for DOI 10.1111/j.1469-8986.2010.01044.x

    View details for Web of Science ID 000285155600014

    View details for PubMedID 20573055

  • Twenty-four hour skin conductance in panic disorder JOURNAL OF PSYCHIATRIC RESEARCH Doberenz, S., Roth, W. T., Wollburg, E., Breuninger, C., Kim, S. 2010; 44 (16): 1137-1147


    Skin conductance, physical activity, ambient temperature and mood were recorded for 24 h in 22 panic disorder (PD) patients and 29 healthy controls. During the day, subjects performed standardized relaxation tests (ARTs). We hypothesized that tonically elevated anticipatory anxiety in PD during waking and sleeping would appear as elevated skin conductance level (SCL) and greater skin conductance (SC) variability. Mean SCL was higher during both usual waking activities and sleeping in PD, but not during the ARTs. Group SC variability differences did not reach significance, perhaps because of variance unrelated to anxiety. Analyses indicated that in the PD group, antidepressant medication reduced mean SCL whereas state anxiety had the opposite effect during the day. Depressive symptoms reported during the day were related to elevated mean SCL on the night of the recording. The rate and extent of SCL deactivation over the night was equal in the two groups. However, PD patients had more frequent interruptions of deactivation that could have arisen from conditioned arousal in response to threat cues during sleep.

    View details for DOI 10.1016/j.jpsychires.2010.04.012

    View details for Web of Science ID 000285952000003

    View details for PubMedID 20537349

  • Temporal stability and coherence of anxiety, dyspnea, and physiological variables in panic disorder BIOLOGICAL PSYCHOLOGY Burkhardt, S. C., Wilhelm, F. H., Meuret, A. E., Blechert, J., Roth, W. T. 2010; 85 (2): 226-232


    Twenty-five panic disorder (PD) patients, 19 social phobics (SP), and 20 healthy controls (HC) sat quietly for 15 min, rating their anxiety and dyspnea every 30s while respiratory, cardiovascular, and electrodermal responses were recorded. No panic attacks were reported. For self-reported anxiety and dyspnea, within-subject variability over time was higher in PD than in SP or HC. In PD within-subject correlations across 30-s epochs were significant for (a) self-reported anxiety versus dyspnea, end-tidal pCO2, minute volume, duty cycle, skin conductance level, and interbeat interval, and for (b) dyspnea versus end-tidal pCO2, minute volume, tidal volume, and inspiratory flow rate. Several positive or negative correlations were greater in PD than in other groups. Thus in PD, experienced anxiety and dyspnea are temporally unstable but are correlated with each other and with fluctuations in respiratory and autonomic variables, even in the absence of panic attacks.

    View details for DOI 10.1016/j.biopsycho.2010.07.005

    View details for Web of Science ID 000283002400006

    View details for PubMedID 20637257

  • Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO2 enriched air in panic disorder, social phobia, and healthy controls BIOLOGICAL PSYCHOLOGY Blechert, J., Wilhelm, F. H., Meuret, A. E., Wilhelm, E. M., Roth, W. T. 2010; 84 (1): 104-111


    Inhalation of carbon dioxide (CO₂) enriched air triggers anxiety in panic disorder (PD) patients, which is often interpreted as a sign of biological vulnerability. However, most studies have not measured respiration in these tasks. We compared patients with PD (n=20) and social phobia (SP, n=19) to healthy controls (n=18) during eight inhalations of 20% CO₂, preceded and followed by two inhalations of room air, while continuously measuring subjective anxiety and dyspnea as well as autonomic and respiratory variables. PD patients showed increased reactivity and delayed recovery during CO₂ inhalations for most measures. Unlike both other groups, the PD group's tidal volume responses did not habituate across CO₂ inhalations. However, PD patients did not differ from SP patients on most other measures, supporting a continuum model of CO₂ sensitivity across anxiety disorders. Both patient groups showed continued reactivity during the last air inhalations, which is unlikely to be due to a biological sensitivity.

    View details for DOI 10.1016/j.biopsycho.2010.01.002

    View details for Web of Science ID 000278466200013

    View details for PubMedID 20064582

  • Change point analysis for longitudinal physiological data: Detection of cardio-respiratory changes preceding panic attacks BIOLOGICAL PSYCHOLOGY Rosenfield, D., Zhou, E., Wilhelm, F. H., Conrad, A., Roth, W. T., Meuret, A. E. 2010; 84 (1): 112-120


    Statistical methods for detecting changes in longitudinal time series of psychophysiological data are limited. ANOVA and mixed models are not designed to detect the existence, timing, or duration of unknown changes in such data. Change point (CP) analysis was developed to detect distinct changes in time series data. Preliminary reports using CP analysis for fMRI data are promising. Here, we illustrate the application of CP analysis for detecting discrete changes in ambulatory, peripheral physiological data leading up to naturally occurring panic attacks (PAs). The CP method was successful in detecting cardio-respiratory changes that preceded the onset of reported PAs. Furthermore, the changes were unique to the pre-PA period, and were not detected in matched non-PA control periods. The efficacy of our CP method was further validated by detecting patterns of change that were consistent with prominent respiratory theories of panic positing a relation between aberrant respiration and panic etiology.

    View details for DOI 10.1016/j.biopsycho.2010.01.020

    View details for Web of Science ID 000278466200014

    View details for PubMedID 20144682



    By comparing efficacious psychological therapies of different kinds, inferences about common effective treatment mechanisms can be made. We selected six therapies for review on the basis of the diversity of their theoretical rationales and evidence for superior efficacy: psychoanalytic psychotherapy, hypercapnic breathing training, hypocapnic breathing training, reprocessing with and without eye-movement desensitization, muscle relaxation, and cognitive behavior therapy. The likely common element of all these therapies is that they reduce the immediate expectancy of a panic attack, disrupting the vicious circle of fearing fear. Modifying expectation is usually regarded as a placebo mechanism in psychotherapy, but may be a specific treatment mechanism for panic. The fact that this is seldom the rationale communicated to the patient creates a moral dilemma: Is it ethical for therapists to mislead patients to help them? Pragmatic justification of a successful practice is a way out of this dilemma. Therapies should be evaluated that deal with expectations directly by promoting positive thinking or by fostering non-expectancy.

    View details for DOI 10.1002/da.20601

    View details for Web of Science ID 000273468300002

    View details for PubMedID 20049938

  • Does improving mood in depressed patients alter factors that may affect cardiovascular disease risk? JOURNAL OF PSYCHIATRIC RESEARCH Taylor, C. B., Conrad, A., Wilhelm, F. H., Strachowski, D., Khaylis, A., Neri, E., Giese-Davis, J., Roth, W. T., Cooke, J. P., Kraemer, H., Spiegel, D. 2009; 43 (16): 1246-1252


    To determine if improvement in mood would ameliorate autonomic dysregulation, HPA dysfunction, typical risk factors and C-reactive protein in depressed patients with elevated cardiovascular disease risk (CVD), 48 depressed participants with elevated cardiovascular risk factors were randomized to a cognitive behavioral intervention (CBT) or a waiting list control (WLC) condition. Twenty non-depressed age and risk-matched controls were also recruited. Traditional risk factors (e.g., lipids, blood pressure) and C-reactive protein were assessed pre- and post-treatment six months later. Subjects also underwent a psychophysiological stress test while cardiovascular physiology was measured. Salivary cortisol was measured during the day and during the psychological stress test. At post-treatment, the CBT subjects were significantly less depressed than WLC subjects. There was no significant difference in change scores on any of the traditional risk factors or C-reactive protein, cortisol measures, or cardiovascular physiology, except for triglyceride levels and heart rate, which were significantly lower in treatment compared to control subjects. The normal controls exhibited no change in the variables measured during the same time. A significant improvement in mood may have little impact on most traditional or atypical risk factors, cortisol or cardiophysiology.

    View details for DOI 10.1016/j.jpsychires.2009.05.006

    View details for Web of Science ID 000272860300002

    View details for PubMedID 19577757

  • Changes in respiration mediate changes in fear of bodily sensations in panic disorder JOURNAL OF PSYCHIATRIC RESEARCH Meuret, A. E., Rosenfield, D., Hofmann, S. G., Suvak, M. K., Roth, W. T. 2009; 43 (6): 634-641


    The purpose of the study was to examine whether changes in pCO(2) mediate changes in fear of bodily sensation (as indexed by anxiety sensitivity) in a bio-behavioral treatment for panic disorder that targets changes in end-tidal pCO(2). Thirty-five panic patients underwent 4 weeks of capnometry-assisted breathing training targeting respiratory dysregulation. Longitudinal mediation analyses of the changes in fear of bodily symptoms over time demonstrated that pCO(2), but not respiration rate, was a partial mediator of the changes in anxiety sensitivity. Results were supported by cross lag panel analyses, which indicated that earlier pCO(2) levels predicted later levels of anxiety sensitivity, but not vice versa. PCO(2) changes also led to changes in respiration rate, questioning the importance of respiration rate in breathing training. The results provide little support for changes in fear of bodily sensations leading to changes in respiration, but rather suggest that breathing training targeting pCO(2) reduced fear of bodily sensations in panic disorder.

    View details for DOI 10.1016/j.jpsychires.2008.08.003

    View details for Web of Science ID 000264613200009

    View details for PubMedID 18835608

  • Changes in pCO(2), Symptoms, and Lung Function of Asthma Patients During Capnometry-assisted Breathing Training APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK Ritz, T., Meuret, A. E., Wilhelm, F. H., Roth, W. T. 2009; 34 (1): 1-6


    In a recent pilot study with asthma patients we demonstrated beneficial outcomes of a breathing training using capnometry biofeedback and paced breathing assistance to increase pCO(2) levels and reduce hyperventilation. Here we explored the time course changes in pCO(2), respiration rate, symptoms and lung function across treatment weeks, in order to determine how long training needs to continue. We analyzed in eight asthma patients whether gains in pCO(2) and reductions in respiration rate achieved in home exercises with paced breathing tapes followed a linear trend across the 4-week treatment period. We also explored the extent to which gains at home were manifest in weekly training sessions in the clinic, in terms of improvement in symptoms and spirometric lung function. The increases in pCO(2) and respiration rate were linear across treatment weeks for home exercises. Similar increases were seen for in-session measurements, together with gradual decreases in symptoms from week to week. Basal lung function remained stable throughout treatment. With our current protocol of paced breathing and capnometry-assisted biofeedback at least 4 weeks are needed to achieve a normalization of pCO(2) levels and reduction in symptoms in asthma patients.

    View details for DOI 10.1007/s10484-008-9070-1

    View details for Web of Science ID 000263523200001

    View details for PubMedID 19048369

  • End-tidal versus transcutaneous measurement of PCO2 during voluntary hypo- and hyperventilation INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Wollburg, E., Roth, W. T., Kim, S. 2009; 71 (2): 103-108


    Recent studies have shown that end-tidal PCO(2) is lower during anxiety and stress, and that changing PCO(2) by altering breathing is therapeutic in panic disorder. However, end-tidal estimation of arterial PCO(2) has drawbacks that might be avoided by the transcutaneous measurement method. Here we compare transcutaneous and end-tidal PCO(2) under different breathing conditions in order to evaluate these methods in terms of their comparability and usability. Healthy volunteers performed two hypoventilation (slow vs. paused breathing) and two hyperventilation tests (25 mm Hg at 18 vs. 30 breaths per minute). Three measurements of PCO(2) (two end-tidal and one transcutaneous device), tidal volume, and respiration rate were recorded. Before and after each test, subjects filled out a symptom questionnaire. The results show that PCO(2) estimated by the two methods was comparable except that for transcutaneous measurement registration of changes in PCO(2) was delayed and absolute levels were much higher. Both methods documented that paused breathing was effective for raising PCO(2), a presumed antidote for anxious hyperventilation. We conclude that since the two methods give comparable results choosing between them for specific applications is principally a matter of whether the time lag of the transcutaneous method is acceptable.

    View details for DOI 10.1016/j.ijpsycho.2008.07.011

    View details for Web of Science ID 000263623800003

    View details for PubMedID 18706460

  • Do blood phobia patients hyperventilate during exposure by breathing faster, deeper, or both? Depression and anxiety Ritz, T., Wilhelm, F. H., Meuret, A. E., Gerlach, A. L., Roth, W. T. 2009; 26 (2): E60-7


    Recently we found that patients with blood-injection-injury (BII) phobia tend to hyperventilate when exposed to feared stimuli. Hyperventilation results from increases in minute ventilation above levels required by metabolic demand and can result from increases in either frequency or depth of breathing, or a combination of both.In order to determine which of these factors contributed most to hyperventilation in BII phobia we analyzed breathing patterns of BII phobia patients (N=12) and non-anxious controls (N=14), recorded with respiratory inductance plethysmography. Participants viewed ten film clips of either an emotionally positive, negative, or neutral quality, as well as surgery and asthma-relevant clips. During five film clips (one from each category) they also tensed their leg muscles.Minute ventilation was markedly increased in blood phobia patients compared to other groups during surgery films. Also, tidal volume and irregularity of tidal volume showed strong increases, while respiration rate was not affected. Leg muscle tension increased ventilation in general but far below the extent brought about by hyperventilation in BII phobia. Patients who were breathing deeper during exposure reported stronger symptoms of dizziness, light-headedness and faintness. In general, patients showed a higher rate of spontaneous sighs throughout all film presentations, but not at baseline.Thus, hyperventilation in blood phobia is produced by excessively deep and irregular breathing and may contribute to fainting responses. Behavioral interventions for BII phobia could benefit from attention to this aspect of dysfunctional breathing.

    View details for DOI 10.1002/da.20466

    View details for PubMedID 19085969

  • Circadian affective, cardiopulmonary, and cortisol variability in depressed and nondepressed individuals at risk for cardiovascular disease JOURNAL OF PSYCHIATRIC RESEARCH Conrad, A., Wilhelm, F. H., Roth, W. T., Spiegel, D., Taylor, C. B. 2008; 42 (9): 769-777


    Depression is a risk factor for cardiovascular disease (CVD) perhaps mediated by hypothalamic-pituitary-adrenal (HPA) axis or vagal dysregulation. We investigated circadian mood variation and HPA-axis and autonomic function in older (55 years) depressed and nondepressed volunteers at risk for CVD by assessing diurnal positive and negative affect (PA, NA), cortisol, and cardiopulmonary variables in 46 moderately depressed and 19 nondepressed volunteers with elevated CVD risk. Participants sat quietly for 5-min periods (10:00, 12:00, 14:00, 17:00, 19:00, and 21:00), and then completed an electronic diary assessing PA and NA. Traditional and respiration-controlled heart rate variability (HRV) variables were computed for these periods as an index of vagal activity. Salivary cortisols were collected at waking, waking+30min, 12:00, 17:00, and 21:00h. Cortisol peaked in the early morning after waking, and gradually declined over the day, but did not differ between groups. PA was lower and NA was higher in the depressed group throughout the day. HRV did not differ between groups. Negative emotions were inversely related to respiratory sinus arrhythmia in nondepressed participants. We conclude that moderately depressed patients do not show abnormal HPA-axis function. Diurnal PA and NA distinguish depressed from nondepressed individuals at risk for CVD, while measures of vagal regulation, even when controlled for physical activity and respiratory confounds, do not. Diurnal mood variations of older individuals at risk for CVD differ from those reported for other groups and daily fluctuations in NA are not related to cardiac autonomic control in depressed individuals.

    View details for DOI 10.1016/j.jpsychires.2007.08.003

    View details for Web of Science ID 000256651600009

    View details for PubMedID 17884093

  • Translational research for panic disorder AMERICAN JOURNAL OF PSYCHIATRY Roth, W. T. 2008; 165 (7): 796-798
  • Psychophysiological reactions to two levels of voluntary hyperventilation in panic disorder JOURNAL OF ANXIETY DISORDERS Wollburg, E., Meuret, A. E., Conrad, A., Roth, W. T., Kim, S. 2008; 22 (5): 886-898


    Panic disorder (PD) patients usually react with more self-reported distress to voluntary hyperventilation (HV) than do comparison groups. Less consistently PD patients manifest physiological differences such as more irregular breathing and slower normalization of lowered end-tidal pCO(2) after HV. To test whether physiological differences before, during, or after HV would be more evident after more intense HV, we designed a study in which 16 PD patients and 16 non-anxious controls hyperventilated for 3 min to 25 mmHg, and another 19 PD patients and another 17 controls to 20 mmHg. Patients reacted to HV to 20 mmHg but not to 25 mmHg with more self-reported symptoms than controls. However, at neither HV intensity were previous findings of irregular breathing and slow normalization of pCO(2) replicated. In general, differences between patients and controls in response to HV were in the cognitive-language rather than in the physiological realm.

    View details for DOI 10.1016/j.janxdis.2007.09.004

    View details for Web of Science ID 000256189100013

    View details for PubMedID 17950571

  • Feedback of end-tidal pCO(2) as a therapeutic approach for panic disorder JOURNAL OF PSYCHIATRIC RESEARCH Meuret, A. E., Wilhelm, F. H., Ritz, T., Roth, W. T. 2008; 42 (7): 560-568


    Given growing evidence that respiratory dysregulation is a central feature of panic disorder (PD) interventions for panic that specifically target respiratory functions could prove clinically useful and scientifically informative. We tested the effectiveness of a new, brief, capnometry-assisted breathing therapy (BRT) on clinical and respiratory measures in PD.Thirty-seven participants with PD with or without agoraphobia were randomly assigned to BRT or to a delayed-treatment control group. Clinical status, respiration rate, and end-tidal pCO(2) were assessed at baseline, post-treatment, 2-month and 12-month follow-up. Respiratory measures were also assessed during homework exercises using a portable capnometer as a feedback device.Significant improvements (in PD severity, agoraphobic avoidance, anxiety sensitivity, disability, and respiratory measures) were seen in treated, but not untreated patients, with moderate to large effect sizes. Improvements were maintained at follow-up. Treatment compliance was high for session attendance and homework exercises; dropouts were few.The data provide preliminary evidence that raising end-tidal pCO(2) by means of capnometry feedback is therapeutically beneficial for panic patients. Replication and extension will be needed to verify this new treatment's efficacy and determine its mechanisms.

    View details for DOI 10.1016/j.jpsychires.2007.06.005

    View details for Web of Science ID 000255424000007

    View details for PubMedID 17681544

  • The psychophysiology of generalized anxiety disorder: 2. Effects of applied relaxation PSYCHOPHYSIOLOGY Conrad, A., Isaac, L., Roth, W. T. 2008; 45 (3): 377-388


    Muscle relaxation therapy assumes that generalized anxiety disorder (GAD) patients lack the ability to relax but can learn this in therapy. We tested this by randomizing 49 GAD patients to 12 weeks of Applied Relaxation (AR) or waiting. Before, during, and after treatment participants underwent relaxation tests. Before treatment, GAD patients were more worried than healthy controls (n=21) and had higher heart rates and lower end-tidal pCO2, but not higher muscle tension (A. Conrad, L. Isaac, & W.T. Roth, 2008). AR resulted in greater symptomatic improvement than waiting. However, 28% of the AR group dropped out of treatment and some patients relapsed at the 6-week follow-up. There was little evidence that AR participants learned to relax in therapy or that a reduction in anxiety was associated with a decrease in activation. We conclude that the clinical effects of AR in improving GAD symptoms are moderate at most and cannot be attributed to reducing muscle tension or autonomic activation.

    View details for DOI 10.1111/j.1469-8986.2007.00644.x

    View details for Web of Science ID 000254792100006

    View details for PubMedID 18221441

  • The psychophysiology of generalized anxiety disorder: 1. Pretreatment characteristics PSYCHOPHYSIOLOGY Conrad, A., Isaac, L., Roth, W. T. 2008; 45 (3): 366-376


    Generalized anxiety disorder (GAD) patients have been reported to have more muscle tension than controls, which has provided a rationale for treating them with muscle relaxation therapies (MRT). We tested this rationale by comparing 49 GAD patients with 21 controls. Participants underwent 5-min relaxation tests, during which they either just sat quietly (QS) or sat quietly and tried to relax (R). GAD patients reported themselves to be more worried during the assessment than the controls, had higher heart rates and lower end-tidal pCO2, but not higher muscle tension as measured by multiple EMGs. QS and R did not differ on most psychological and physiological measures, indicating that intention to relax did not affect speed of relaxation. In the GAD group, self-reported anxiety was not associated with electromyographic or autonomic measures. We conclude that GAD is not necessarily characterized by chronic muscle tension, and that this rationale for MRT should be reconsidered.

    View details for DOI 10.1111/j.1469-8986.2007.00601.x

    View details for Web of Science ID 000254792100005

    View details for PubMedID 18221449

  • Sympathetic activation in broadly defined generalized anxiety disorder JOURNAL OF PSYCHIATRIC RESEARCH Roth, W. T., Doberenz, S., Dietel, A., Conrad, A., Mueller, A., Wollburg, E., Meuret, A. E., Taylor, C. B., Kim, S. 2008; 42 (3): 205-212


    The definition of generalized anxiety disorder (GAD) has been narrowed in successive editions of DSM by emphasizing intrusive worry and deemphasizing somatic symptoms of hyperarousal. We tried to determine the clinical characteristics of more broadly defined chronically anxious patients, and whether they would show physiological signs of sympathetic activation. A group whose chief complaint was frequent, unpleasant tension over at least the last six weeks for which they desired treatment, was compared with a group who described themselves as calm. Participants were assessed with structured interviews and questionnaires. Finger skin conductance, motor activity, and ambient temperature were measured for 24h. Results show that during waking and in bed at night, runs of continuous minute-by-minute skin conductance level (SCL) declines were skewed towards being shorter in the tense group than in the calm group. In addition, during waking, distributions of minute SCLs were skewed towards higher levels in the tense group, although overall mean SCL did not differ. Thus, the tense group showed a failure to periodically reduce sympathetic tone, presumably a corollary of failure to relax. We conclude that broader GAD criteria include a substantial number of chronically anxious and hyperaroused patients who do not fall within standard criteria. Such patients deserve attention by clinicians and researchers.

    View details for DOI 10.1016/j.jpsychires.2006.12.003

    View details for Web of Science ID 000253397900005

    View details for PubMedID 17250853

  • Cardiovascular, electrodermal, and respiratory response patterns to fear- and sadness-inducing films PSYCHOPHYSIOLOGY Kreibig, S. D., Wilhelm, F. H., Roth, W. T., Gross, J. J. 2007; 44 (5): 787-806


    Responses to fear- and sadness-inducing films were assessed using a broad range of cardiovascular (heart rate, T-wave amplitude, low- and high-frequency heart rate variability, stroke volume, preejection period, left-ventricular ejection time, Heather index, blood pressure, pulse amplitude and transit time, and finger temperature), electrodermal (level, response rate, and response amplitude), and respiratory (rate, tidal volume and its variability, inspiratory flow rate, duty cycle, and end-tidal pCO(2)) measures. Subjective emotional experience and facial behavior (Corrugator Supercilii and Zygomaticus Major EMG) served as control measures. Results indicated robust differential physiological response patterns for fear, sadness, and neutral (mean classification accuracy 85%). Findings are discussed in terms of the fight-flight and conservation-withdrawal responses and possible limitations of a valence-arousal categorization of emotion in affective space.

    View details for DOI 10.1111/j.1469-8986.2007.00550.x

    View details for Web of Science ID 000249002200013

    View details for PubMedID 17598878

  • Psychophysiological effects of breathing instructions for stress management APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK Conrad, A., Mueller, A., Doberenz, S., Kim, S., Meuret, A. E., Wollburg, E., Roth, W. T. 2007; 32 (2): 89-98


    Stressed and tense individuals often are recommended to change the way they breathe. However, psychophysiological effects of breathing instructions on respiration are rarely measured. We tested the immediate effects of short and simple breathing instructions in 13 people seeking treatment for panic disorder, 15 people complaining of daily tension, and 15 controls. Participants underwent a 3-hour laboratory session during which instructions to direct attention to breathing and anti-hyperventilation instructions to breathe more slowly, shallowly, or both were given. Respiratory, cardiac, and electrodermal measures were recorded. The anti-hyperventilation instructions failed to raise end-tidal pCO(2) above initial baseline levels for any of the groups because changes in respiratory rate were compensated for by changes in tidal volume and vice versa. Paying attention to breathing significantly reduced respiratory rate and decreased tidal volume instability compared to the other instructions. Shallow breathing made all groups more anxious than did other instructions. Heart rate and skin conductance were not differentially affected by instructions. We conclude that simple and short instructions to alter breathing do not change respiratory or autonomic measures in the direction of relaxation, except for attention to breathing, which increases respiratory stability. To understand the results of breathing instructions for stress and anxiety management, respiration needs to be monitored physiologically.

    View details for DOI 10.1007/s10484-007-9034-x

    View details for Web of Science ID 000247932100002

    View details for PubMedID 17520360

  • Targeting pCO(2) in asthma: Pilot evaluation of a capnometry-assisted breathing training APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK Meuret, A. E., Ritz, T., Wilhelm, F. H., Roth, W. T. 2007; 32 (2): 99-109


    This pilot study aimed to evaluate the feasibility and potential benefits of a novel biofeedback breathing training for achieving sustained increases in pCO(2) levels.Twelve asthma patients were randomly assigned to an immediate 4-week treatment group or waiting list control. Patients were instructed to modify their respiration in order to change levels of end-tidal pCO(2) using a hand-held capnometer. Treatment outcome was assessed in frequency and distress of symptoms, asthma control, lung function, and variability of peak expiratory flow (PEF).We found stable increases in pCO(2) and reductions in respiration rate during treatment and 2-month follow-up. Mean pCO(2) levels rose from a hypocapnic to a normocapnic range at follow-up. Frequency and distress of symptoms was reduced and reported asthma control increased. In addition, mean PEF variability decreased significantly in the treatment group.Our pilot intervention provided evidence for the feasibility of pCO(2)-biofeedback training in asthma patients.

    View details for DOI 10.1007/s10484-007-9036-8

    View details for Web of Science ID 000247932100003

    View details for PubMedID 17564826

  • Physiological evaluation of psychological treatments for anxiety. Expert review of neurotherapeutics Wollburg, E., Kim, S., Conrad, A., Roth, W. T. 2007; 7 (2): 129-141


    Classification of mental disorders has been greatly influenced by a medical model postulating biological abnormalities that underlie its divisions. Particularly in anxiety disorders, physiological symptoms are part of the Diagnostic and Statistical Manual criteria. Therefore, successful therapy should influence physiological as well as cognitive-verbal expressions of anxiety. Nevertheless, despite the well-known limitations of self-report, physiological outcome measures have only occasionally been employed. We searched the literature for treatment studies that attempted to make a physiological argument for the efficacy of a psychological treatment for anxiety. Our search found only a few methodologically sound examples, where normalization of self-report and physiological measures corresponded. The most convincing studies dealt with the treatment of specific phobias and post-traumatic stress disorder.

    View details for PubMedID 17286547

  • Muscle relaxation therapy for anxiety disorders: It works but how? JOURNAL OF ANXIETY DISORDERS Conrad, A., Roth, W. T. 2007; 21 (3): 243-264


    Muscle relaxation therapy (MRT) has continued to play an important role in the modern treatment of anxiety disorders. Abbreviations of the original progressive MRT protocol [Jacobson, E. (1938). Progressive relaxation (2nd ed.). Chicago: University of Chicago Press] have been found to be effective in panic disorder (PD) and generalized anxiety disorder (GAD). This review describes the most common MRT techniques, summarizes recent evidence of their effectiveness in treating anxiety, and explains their rationale and physiological basis. We conclude that although GAD and PD patients may exhibit elevated muscle tension and abnormal autonomic and respiratory measures during laboratory baseline assessments, the available evidence does not allow us to conclude that physiological activation decreases over the course of MRT in GAD and PD patients, even when patients report becoming less anxious. Better-designed studies will be required to identify the mechanisms of MRT and to advance clinical practice.

    View details for DOI 10.1016/j.janxdis.2006.08.001

    View details for Web of Science ID 000245868500001

    View details for PubMedID 16949248

  • The Driving Cognitions Questionnaire: Development and preliminary psychometric properties JOURNAL OF ANXIETY DISORDERS Ehlers, A., Taylor, J. E., Ehring, T., Hofmann, S. G., Deane, F. P., Roth, W. T., Podd, J. V. 2007; 21 (4): 493-509


    Recent research has suggested that fear of driving is common in the general population. People may have various concerns when driving, and instruments for the assessment of these concerns are lacking. The present paper describes the development and preliminary evaluation of the Driving Cognitions Questionnaire (DCQ). The DCQ is a 20-item scale that measures three areas of driving-related concerns--panic-related, accident-related, and social concerns. In three separate samples from different countries (n=69, 100, and 78), the scale showed good internal consistency and substantial correlations with measures of the severity of driving fear. It discriminated well between people with and without driving phobia. It also showed convergent validity with other measures. The questionnaire shows promise for use in research and clinical practice.

    View details for DOI 10.1016/j.janxdis.2006.08.002

    View details for Web of Science ID 000246948800002

    View details for PubMedID 16982173

  • Panic attack symptom dimensions and their relationship to illness characteristics in panic disorder JOURNAL OF PSYCHIATRIC RESEARCH Meuret, A. E., White, K. S., Ritz, T., Roth, W. T., Hofmann, S. G., Brown, T. A. 2006; 40 (6): 520-527


    Subtyping panic disorder by predominant symptom constellations, such as cognitive or respiratory, has been done for some time, but criteria have varied considerably between studies. We sought to identify statistically symptom dimensions from intensity ratings of 13 DSM-IV panic symptoms in 343 panic patients interviewed with the Anxiety Disorders Interview Schedule for DSM-IV Lifetime Version. We then explored the relation of symptom dimensions to selected illness characteristics. Ratings were submitted to exploratory maximum likelihood factor analysis with a Promax rotation. A three-factor solution was found to account best for the variance. Symptoms loading highest on the first factor were palpitations, shortness of breath, choking, chest pain, and numbness, which define a cardio-respiratory type (with fear of dying). Symptoms loading highest on the second factor were sweating, trembling, nausea, chills/hot flashes, and dizziness, which defines a mixed somatic subtype. Symptoms loading highest on the third factor were feeling of unreality, fear of going crazy, and fear of losing control, which defines a cognitive subtype. Subscales based on these factors showed moderate intercorrelations. In a series of hierarchical multiple regression analyses, the cardio-respiratory subscale was a strong predictor of panic severity, frequency of panic attacks, and agoraphobic avoidance, while the cognitive subscale mostly predicted worry due to panic. In addition, patients with comorbid asthma had higher scores on the cardio-respiratory subscale. We conclude that partly independent panic symptom dimensions can be identified that have different implications for severity and control of panic disorder.

    View details for DOI 10.1016/j.jpsychires.2005.09.006

    View details for Web of Science ID 000240250000007

    View details for PubMedID 16293263

  • Psychophysiological and cortisol responses to psychological stress in depressed and nondepressed older men and women with elevated cardiovascular disease risk PSYCHOSOMATIC MEDICINE Taylor, C. B., Conrad, A., Wilhelm, F. H., Neri, E., DeLorenzo, A., Kramer, M. A., Giese-Davis, J., Roth, W. T., Oka, R., Cooke, J. P., Kraemer, H., Spiegel, D. 2006; 68 (4): 538-546


    The objective of this study was to compare psychophysiological and cortisol reactions to psychological stress in older depressed and nondepressed patients at risk for cardiovascular disease (CVD).Forty-eight depressed participants and 20 controls with elevated cardiovascular risk factors underwent a psychological stress test during which cardiovascular variables were measured. Salivary cortisol was collected after each test segment. Traditional (e.g., lipids) and atypical (e.g., C-reactive protein) CVD risk factors were also obtained.At baseline, the groups did not differ on lipid levels, flow-mediated vasodilation, body mass index, or asymmetric dimethylarginine. However, the depressed patients had significantly higher C-reactive protein levels. Contrary to our hypothesis, there were no differences in baseline cortisol levels or diurnal cortisol slopes, but depressed patients showed significantly lower cortisol levels during the stress test (p = .03) and less cortisol response to stress. Compared with nondepressed subjects, depressed subjects also showed lower levels of respiratory sinus arrhythmia (RSA(TF)) during the stress test (p = .02).In this sample, older depressed subjects with elevated risk for CVD exhibited a hypocortisol response to acute stress. This impaired cortisol response might contribute to chronic inflammation (as reflected in the elevated C-reactive proteins in depressed patients) and in other ways increase CVD risk. The reduced RSA(TF) activity may also increase CVD risk in depressed patients through impaired autonomic nervous system response to cardiophysiological demands.

    View details for DOI 10.1097/01.psy.0000222372.16274.92

    View details for Web of Science ID 000239330600005

    View details for PubMedID 16868262

  • Physiological markers for anxiety: Panic disorder and phobias INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Roth, W. T. 2005; 58 (2-3): 190-198


    Physiological activation is a cardinal symptom of anxiety, although physiological measurement is still not used for psychiatric diagnosis. An ambulatory study of phobics who were afraid of highway driving showed a concordance between self-reported anxiety during driving, autonomic activation, hypocapnia, and sighing respiration. Patients with panic attacks do not exhibit autonomic activation when they are quietly sitting and not having panic attacks, but do have the same respiratory abnormalities as driving phobics, suggesting that these abnormalities could be a marker for panic disorder. Such abnormalities are compatible with both the false suffocation alarm (D. Klein) and hyperventilation (R. Ley) theories of panic. Hypocapnia, however, is often absent during full-blown panic attacks. Since activation functions as preparation for physical activity, it may not occur when a patient has learned that avoidance of fear by flight or fight is futile. We developed a capnometry feedback assisted breathing training therapy for panic disorder designed to reduce hyperventilation and making breathing regular. Without feedback, conventional therapeutic breathing instructions may actually increase hyperventilation by increasing dyspnea. Five weekly therapy sessions accompanied by daily home practice with a capnometer produced marked clinical improvement compared to changes in an untreated group. Improvement was sustained over a 12-month follow-up period. The therapist avoided any statements or procedures designed to alter cognitions. Improvement occurred regardless of whether patients initially reported mostly respiratory or non-respiratory symptoms during their attacks. There is evidence that modifying any of the three systems comprising a fear network can be therapeutic, as exemplified by cognitive therapy modifying thoughts, exposure therapy modifying avoidance, and breathing training procedures modifying pCO(2).

    View details for DOI 10.1016/j.ijpsycho.2005.01.015

    View details for Web of Science ID 000233383000010

    View details for PubMedID 16137780

  • End-tidal pCO(2) in blood phobics during viewing of emotion- and disease-related films PSYCHOSOMATIC MEDICINE Ritz, T., Wilhelm, F. H., Gerlach, A. L., Kullowatz, A., Roth, W. T. 2005; 67 (4): 661-668


    Many patients with blood, injection, and injury (BII) phobia respond to specific stimuli with vasovagal dysregulation and fainting. However, little is known about the role of hyperventilation in the distress of these patients. Hyperventilation, defined by subnormal arterial pCO2 levels, induces anxiety and may promote the development of fainting. We studied end-tidal pCO2 in 12 patients with BII phobia and 14 nonanxious controls during presentation of emotional films.Ten film clips were shown, two in each of 5 categories: pleasant, unpleasant, neutral, BII-related (surgery), and asthma-related (portraying labored breathing). For each subject, two subsets were created, each containing one clip from each category. For one subset, the instruction was simply to view the film, and for the other subset, to view the film while tensing the leg muscles. PCO2, heart rate, blood pressure, and leg electromyogram were recorded continuously during viewing, and self-report of symptoms and emotion was collected after each film.Patients reported the greatest anxiety and disgust during surgery films. PCO2 was relatively stable throughout all categories except surgery films, during which minima were below 30 mm Hg, indicating significant hypocapnia. Cardiovascular variables suggested biphasic patterns in two patients with BII phobia. These patients, together with one additional patient and one control who were close to fainting after or during one surgery film, also showed a marked fall in pCO2) Leg muscle tension raised heart rate and systolic blood pressure for all films, but was not related to near-fainting or endurance in surgery film viewing.Hyperventilation is part of the fear response of patients with BII phobia, but was transitory in experimental fear induction using surgery films. Its role in real-life exposure and fainting deserves further study.

    View details for DOI 10.1097/01.psy.0000170339.06281.07

    View details for Web of Science ID 000230830600025

    View details for PubMedID 16046385

  • Voluntary hyperventilation in the treatment of panic disorder - functions of hyperventilation, their implications for breathing training, and recommendations for standardization CLINICAL PSYCHOLOGY REVIEW Meuret, A. E., Ritz, T., Wilhelm, F. H., Roth, W. T. 2005; 25 (3): 285-306


    Hyperventilation has numerous theoretical and empirical links to anxiety and panic. Voluntary hyperventilation (VH) tests have been applied experimentally to understand psychological and physiological mechanisms that produce and maintain anxiety, and therapeutically in the treatment of anxiety disorders. From the theoretical perspective of hyperventilation theories of anxiety, VH is useful diagnostically to the clinician and educationally to the patient. From the theoretical perspective of cognitive-behavior therapy, VH is a way to expose patients with panic disorder to sensations associated with panic and to activate catastrophic cognitions that need restructuring. Here we review panic disorder treatment studies using breathing training that have included VH. We differentiate the roles of VH in diagnosis, education about symptoms, training of breathing strategies, interoceptive exposure, and outcome measurement--discussing methodological issues specific to these roles and VH test reliability and validity. We propose how VH procedures might be standardized in future studies.

    View details for DOI 10.1016/j.cpr.2005.01.002

    View details for Web of Science ID 000228619200002

    View details for PubMedID 15792851

  • Are current theories of panic falsifiable? PSYCHOLOGICAL BULLETIN Roth, W. T., Wilhelm, F. H., Pettit, D. 2005; 131 (2): 171-192


    The authors examine 6 theories of panic attacks as to whether empirical approaches are capable of falsifying them and their heuristic value. The authors conclude that the catastrophic cognitions theory is least falsifiable because of the elusive nature of thoughts but that it has greatly stimulated research and therapy. The vicious circle theory is falsifiable only if the frightening internal sensations are specified. The 3-alarms theory postulates an indeterminate classification of attacks. Hyperventilation theory has been falsified. The suffocation false alarm theory lacks biological parameters that unambiguously index dyspnea or its distinction between anticipatory and panic anxiety. Some correspondences postulated between clinical phenomena and brain areas by the neuroanatomical hypothesis may be falsifiable if panic does not depend on specific thoughts. All these theories have heuristic value, and their unfalsifiable aspects are capable of modification.

    View details for DOI 10.1037/0033-2909.1312.2.171

    View details for Web of Science ID 000227423200001

    View details for PubMedID 15740414

  • Psychophysiological assessment during exposure in driving phobic patients JOURNAL OF ABNORMAL PSYCHOLOGY Alpers, G. W., Wilhelm, F. H., Roth, W. T. 2005; 114 (1): 126-139


    A comprehensive assessment of fear or anxiety requires measurement of both self-report and physiological responses. Respiratory abnormalities have been rarely examined during real-life exposure, although they are an integral part of fear. Twenty-one women with a specific driving phobia and 17 nonphobic women were psychophysiologically monitored during 2 highway-driving sessions; phobic women completed an additional session. Respiratory movements, end-tidal partial pressure of carbon dioxide, an electrocardiogram, skin conductance, and skin temperature were recorded. Phobic patients differed from control participants both physiologically and experientially before, during, and after exposure. Effect size during exposure was large for the authors' measure of hyperventilation. Discriminant analysis indicated that multiple physiological measures contributed nonredundant information and correctly classified 95% of phobic and control participants. Thus, selected respiratory and autonomic measures are valid diagnostic and therapeutic outcome criteria for this situational phobia.

    View details for DOI 10.1037/0021-843X.114.1.126

    View details for Web of Science ID 000227146600013

    View details for PubMedID 15709819

  • Behavioral interventions in asthma biofeedback techniques JOURNAL OF PSYCHOSOMATIC RESEARCH Ritz, T., Dahme, B., Roth, W. T. 2004; 56 (6): 711-720


    Biofeedback techniques have long been recommended as an adjunctive treatment for bronchial asthma. Techniques that target lung function directly, or indirectly by altering facial muscle tension, heart rate, heart rate variability (HRV) or inspiratory volume together with accessory muscle tension, have been proposed. We review evidence for the effectiveness of these biofeedback interventions and discuss the psychophysiological rationale behind individual techniques.Controlled studies of biofeedback in asthma were retrieved using relevant search engines and reference lists of published articles. Effect sizes comparing intervention with control groups were calculated where appropriate.Most of the studies suffer from methodological inadequacies or poor reporting of methods and results. Interventions targeting respiratory resistance directly have yielded only small and inconsistent changes in lung function and are difficult to implement without producing dynamic hyperinflation. Biofeedback-assisted facial muscle relaxation as an indirect intervention has yielded mixed results across studies, with only half of the studies showing significant albeit very small and clinically irrelevant improvements in lung function. The underlying physiological assumptions of the technique are questionable in the light of current knowledge of respiratory physiology. For other indirect techniques, only preliminary evidence of small effects is available.Currently, there is little good evidence that biofeedback techniques can contribute substantially to the treatment of asthma.

    View details for DOI 10.1016/S0022-3999(03)00131-4

    View details for Web of Science ID 000222284200010

    View details for PubMedID 15193969

  • Deficient response modulation of event-related brain potentials in schizophrenia CURRENT OPINION IN PSYCHIATRY Ford, J. M., Roth, W. T. 2004; 17 (2): 91-96
  • Respiratory feedback for treating panic disorder JOURNAL OF CLINICAL PSYCHOLOGY Meuret, A. E., Wilhelm, F. H., Roth, W. T. 2004; 60 (2): 197-207


    Panic disorder patients often complain of shortness of breath or other respiratory complaints, which has been used as evidence for both hyperventilation and false suffocation alarm theories of panic. Training patients to change their breathing patterns is a common intervention, but breathing rarely has been measured objectively in assessing the patient or monitoring therapy results. We report a new breathing training method that makes use of respiratory biofeedback to teach individuals to modify four respiratory characteristics: increased ventilation (Respiratory Rate x Tidal Volume), breath-to-breath irregularity in rate and depth, and chest breathing. As illustrated by a composite case, feedback of respiratory rate and end-tidal pCO2 can facilitate voluntary control of respiration and reduce symptoms. Respiratory monitoring may provide relevant diagnostic, prognostic, and outcome information.

    View details for DOI 10.1002/jclp.10245

    View details for Web of Science ID 000188430200007

    View details for PubMedID 14724927

  • The LifeShirt - An advanced system for ambulatory measurement of respiratory and cardiac function BEHAVIOR MODIFICATION Wilhelm, F. H., Roth, W. T., Sackner, M. A. 2003; 27 (5): 671-691


    An accurate ambulatory breathing monitor is needed to observe acute respiratory changes in patients with medical or psychological disorders outside the clinic (e.g., hyperventilation during panic or apneas during sleep). Significant limitations of existing monitors are size, troublesome operation, and difficulty holding chest and abdomen bands in place during 24-hour recordings. Recently, a garment has been developed with embedded inductive plethysmography sensors for continuous ambulatory monitoring of respiration, heart activity, inductive cardiography, motility, postural changes, and other functions. The signals are displayed and stored on a handheld computer (Visor), and then analyzed offline, extracting more than 40 clinical parameters relating to cardiorespiratory function (e.g., heart rate, respiratory sinus arrhythmia, tidal volume, stroke volume, pre-ejection period, apnea-hypopnea index, thoraco-abdominal coordination, sighing). The device also serves as an electronic diary of symptoms, moods, and activities. This advanced system may open a new era in ambulatory monitoring for clinical practice and scientific research.

    View details for DOI 10.1177/0145445503256321

    View details for Web of Science ID 000185192800006

    View details for PubMedID 14531161

  • Behavioral interventions in asthma - Breathing training BEHAVIOR MODIFICATION Ritz, T., Roth, W. T. 2003; 27 (5): 710-730


    Breathing exercises are frequently recommended as an adjunctive treatment for asthma. A review of the current literature found little that is systematic documenting the benefits of these techniques in asthma patients. The physiological rationale of abdominal breathing in asthma is not clear, and adverse effects have been reported in chronic obstructive states. Theoretical analysis and empirical observations suggest positive effects of pursed-lip breathing and nasal breathing but clinical evidence is lacking. Modification of breathing patterns alone does not yield any significant benefit. There is limited evidence that inspiratory muscle training and hypoventilation training can help reduce medication consumption, in particular beta-adrenergic inhaler use. Breathing exercises do not seem to have any substantial effect on parameters of basal lung function. Additional research is needed on the psychological and physiological mechanisms of individual breathing techniques in asthma, differential effects in subgroups of asthma patients, and the generalization of training effects on daily life.

    View details for DOI 10.1177/0145445503256323

    View details for Web of Science ID 000185192800008

    View details for PubMedID 14531163

  • Breathing training for treating panic disorder - Useful intervention or impediment? BEHAVIOR MODIFICATION Meuret, A. E., Wilhelm, F. H., Ritz, T., Roth, W. T. 2003; 27 (5): 731-754


    Breathing training (BT) is commonly used for treatment of panic disorder. We identified nine studies that reported the outcome of BT. Overall, the published studies of BT are not sufficiently compelling to allow an unequivocal judgment of whether such techniques are beneficial. This article discusses problems with the underlying rationale, study design, and techniques used in BT, and it identifies factors that may have determined therapy outcomes. The idea that hypocapnia and respiratory irregularities are underlying factors in the development of panic implies that these factors should be monitored physiologically throughout therapy. Techniques taught in BT must take account of respiration rate and tidal volume in the regulation of blood gases (pCO2). More studies are needed that are designed to measure the efficacy of BT using an adequate rationale and methodology. Claims that BT should be rejected in favor of cognitive or other forms of intervention are premature.

    View details for DOI 10.1177/0145445503256324

    View details for Web of Science ID 000185192800009

    View details for PubMedID 14531164

  • Salivary cortisol response during exposure treatment in driving phobics PSYCHOSOMATIC MEDICINE Alpers, G. W., Abelson, J. L., Wilhelm, F. H., Roth, W. T. 2003; 65 (4): 679-687


    Extensive research on the hypothalamic-pituitary-adrenal (HPA) axis response to stress has not clarified whether that axis is activated by phobic anxiety. We addressed this issue by measuring cortisol in situational phobics during exposure treatment.Salivary cortisol was measured in 11 driving phobics before and during three exposure sessions involving driving on crowded limited-access highways and compared with levels measured in 13 healthy controls before and during two sessions of driving on the same highways. For each subject, data collected in the same time period on a comparison nondriving day served as an individual baseline from which cortisol response scores were calculated.Cortisol levels of driving phobics and controls did not differ on the comparison day. Phobics also had normal cortisol response scores on awakening on the mornings of the exposures but these were already increased 1 hour before coming to the treatment sessions. Phobics had significantly greater cortisol response scores during driving exposure and during quiet sitting periods before and afterward. These greater responses generally paralleled increases in self-reported anxiety. At the first exposure session, effect sizes for differences in cortisol response scores between the two groups were large. Initial exposure to driving in the first session evoked the largest responses.The data demonstrate that the HPA axis can be strongly activated by exposure to, and anticipation of, a phobic situation.

    View details for DOI 10.1097/01.PSY.0000073872.85623.0C

    View details for Web of Science ID 000184362200030

    View details for PubMedID 12883122

  • Predictors of response in anxiety disorders PSYCHIATRIC CLINICS OF NORTH AMERICA Solvason, H. B., ERNST, H., Roth, W. 2003; 26 (2): 411-?


    Anxiety disorder variables such as duration, severity of illness, and comorbidity with other anxiety or mood disorders appear to identify individuals who are at the greatest risk of treatment nonresponse. Conversely, in accord with clinical experience, shorter periods of illness, less severe illness, being treatment naive, and the absence of comorbidity tend to identify patients who are likely to respond robustly to medication management. Symptom clusters in OCD and PTSD are promising as a means of stratifying those more likely to respond to standard pharmacologic treatment. The presence of hoarding or sexual obsessions seems to presage poorer response in OCD, while the presence of dissociative symptoms in PTSD has been linked to high nonspecific treatment response rates to placebo. Genotyping individuals with respect to genes that are thought to have an important role in the underlying disease process, such as the work with the 5HTTL-PR allele, is exciting and is perhaps the first glimmer of using genotyping to identify treatment strategies or to predict the likelihood or speed of response. The use of neuroimaging as a means of identifying individuals who may respond favorably to pharmacologic or neurosurgical intervention is still in its infancy. As a strategy, it may help combine symptom severity and response variables into a clear neurobiologic vulnerability model of illness. In the future, it may be possible to identify specific treatment interventions for specific patterns of abnormal metabolic rates in certain areas of the brain. However, it should be emphasized that such an approach has not been empirically demonstrated in a rigorous experimental context at this time.

    View details for DOI 10.1016/S0193-953X(03)00027-3

    View details for Web of Science ID 000182929300008

    View details for PubMedID 12778841

  • Detection of speaking with a new respiratory inductive plethysmography system BIOMEDICAL SCIENCES INSTRUMENTATION, VOL 39 Wilhelm, F. H., Handke, E. M., Roth, W. T. 2003; 39: 136-141


    The LifeShirt system, a garment with integrated sensors connected to a handheld computer, allows recording of a wide variety of clinically important cardiorespiratory data continuously for extended periods outside the laboratory or clinic. The device includes sensors for assessment of physical activity and posture since both can affect physiological activation and need to be controlled. Speaking is another potential confounding factor in the interpretation of physiological data. Auditory speech recording is problematic because it can pick up sources other than the person's voice (external microphone) or is obtrusive (throat microphone). The abdominal and thoracic calibrated respiratory inductive plethysmography (RIP) sensors integrated in the LifeShirt system might be an adequate alternative for detecting speech. In a laboratory experiment we determined respiratory parameters indicative of speech. Eighteen subjects were instructed to sit quietly, write, and speak continuously, for 4 min each. Nine parameters were derived from the RIP signals and averaged over each minute. In addition, nine variability parameters were computed as their coefficients of breath-by-breath variation. Inspiratory/expiratory time (IE-ratio) best distinguished speaking from writing with 98% correct classification at a cutoff criterion of 0.52. This criterion was equally successful in distinguishing speaking from sitting quietly. Discriminant analyses indicated that linear combinations of IE-ratio and a variety of other parameters did not reliably improve classification accuracy across tasks and replications. These results demonstrate the high efficacy of RIP-derived IE-ratio for speech detection and suggest that auditory recording is not necessary for detection of speech in ambulatory assessment.

    View details for Web of Science ID 000182321800024

    View details for PubMedID 12724882

  • Embarrassment and social phobia: the role of parasympathetic activation JOURNAL OF ANXIETY DISORDERS Gerlach, A. L., Wilhelm, F. H., Roth, W. T. 2003; 17 (2): 197-210


    The few studies on the psychophysiology of embarrassment have suggested involvement of parasympathetic activation. However, blushing, the hallmark of embarrassment and a prominent symptom in social phobia, is more likely to be produced by cervical sympathetic outflow. Hitherto, there has been no evidence of parasympathetic innervation of the facial blood vessels. In this study, a group of social phobics and control participants watched, together with a 2-person audience, a previously made videotape of themselves singing a children's song. Self-report measures confirmed that this task induced embarrassment. While two measures of respiratory sinus arrhythmia (RSA) during the task did not indicate heightened parasympathetic tone, increased heart rate (HR) and skin conductance marked sympathetic activation. Thus, our data do not support the notion that an increase in parasympathetic activation plays a significant role in social phobia and embarrassment. Social anxiety and embarrassment both resulted in sympathetic activation.

    View details for Web of Science ID 000181646200005

    View details for PubMedID 12614662

  • Reduced communication between frontal and temporal lobes during talking in schizophrenia BIOLOGICAL PSYCHIATRY Ford, J. M., Mathalon, D. H., Whitfield, S., Faustman, W. O., Roth, W. T. 2002; 51 (6): 485-492


    Communication between the frontal lobes, where speech and verbal thoughts are generated, and the temporal lobes, where they are perceived, may occur through the action of a corollary discharge. Its dysfunction may underlie failure to recognize inner speech as self-generated and account for auditory hallucinations in schizophrenia.Electroencephalogram was recorded from 10 healthy adults and 12 patients with schizophrenia (DSM-IV) in two conditions: talking aloud and listening to their own played-back speech. Event-related electroencephalogram coherence to acoustic stimuli presented during both conditions was calculated between frontal and temporal pairs, for delta, theta, alpha, beta, and gamma frequency bands.Talking produced greater coherence than listening between frontal-temporal regions in all frequency bands; however, in the lower frequencies (delta and theta), there were significant interactions of group and condition. This finding revealed that patients failed to show an increase in coherence during talking, especially over the speech production and speech reception areas of the left hemisphere, and especially in patients prone to hallucinate.Reduced fronto-temporal functional connectivity may contribute to the misattribution of inner thoughts to external voices in schizophrenia.

    View details for Web of Science ID 000174739000008

    View details for PubMedID 11922884

  • High altitudes, anxiety, and panic attacks: Is there a relationship? DEPRESSION AND ANXIETY Roth, W. T., Gomolla, A., Meuret, A. E., Alpers, G. W., Handke, E. M., Wilhelm, F. H. 2002; 16 (2): 51-58


    People exposed to high altitudes often experience somatic symptoms triggered by hypoxia, such as breathlessness, palpitations, dizziness, headache, and insomnia. Most of the symptoms are identical to those reported in panic attacks or severe anxiety. Potential causal links between adaptation to altitude and anxiety are apparent in all three leading models of panic, namely, hyperventilation (hypoxia leads to hypocapnia), suffocation false alarms (hypoxia counteracted to some extent by hypocapnia), and cognitive misinterpretations (symptoms from hypoxia and hypocapnia interpreted as dangerous). Furthermore, exposure to high altitudes produces respiratory disturbances during sleep in normals similar to those in panic disorder at low altitudes. In spite of these connections and their clinical importance, evidence for precipitation of panic attacks or more gradual increases in anxiety during altitude exposure is meager. We suggest some improvements that could be made in the design of future studies, possible tests of some of the theoretical causal links, and possible treatment applications, such as systematic exposure of panic patients to high altitude.

    View details for DOI 10.1002/da.10059

    View details for Web of Science ID 000178260700001

    View details for PubMedID 12219335

  • Neurophysiological evidence of corollary discharge dysfunction in schizophrenia AMERICAN JOURNAL OF PSYCHIATRY Ford, J. M., Mathalon, D. H., Heinks, T., Kalba, S., Faustman, W. O., Roth, W. T. 2001; 158 (12): 2069-2071


    Speaking is hypothesized to generate a corollary discharge of motor speech commands transmitted to the auditory cortex, dampening its response to self-generated speech sounds. Event-related potentials were used to test whether failures of corollary discharge during speech contribute to the pathophysiology of schizophrenia.The N1 component of the event-related potential elicited by vowels was recorded while the vowels were spoken by seven patients with schizophrenia and seven healthy comparison subjects and while the same vowels were played back.In the healthy subjects, the N1 elicited by spoken vowels was smaller than the N1 elicited by played-back vowels. This reduction in N1 elicited by spoken vowels was not observed in the patients with schizophrenia.These findings provide direct neurophysiological evidence for a corollary discharge that dampens sensory responses to self-generated, relative to externally presented, percepts in healthy comparison subjects and its failure in patients with schizophrenia.

    View details for Web of Science ID 000172452100023

    View details for PubMedID 11729029

  • Cortical responsiveness during inner speech in schizophrenia: An event-related potential study AMERICAN JOURNAL OF PSYCHIATRY Ford, J. M., Mathalon, D. H., Kalba, S., Whitfield, S., Faustman, W. O., Roth, W. T. 2001; 158 (11): 1914-1916


    The study assessed the effects of inner speech on auditory cortical responsiveness in schizophrenia.Comparison subjects (N=15) and patients with schizophrenia (N=15) were presented with acoustic and visual stimuli during three conditions: while subjects were silent, when spontaneous inner speech might occur; during directed inner speech, while subjects repeated a statement silently to themselves; and while subjects listened to recorded speech. N1 event-related potentials were recorded during the three conditions.N1 event-related potentials elicited by acoustic stimuli, but not by visual stimuli, were lower during directed inner speech than during the silent baseline condition in the comparison subjects but not in the patients.Abnormal auditory cortical responsiveness to inner speech in patients with schizophrenia may be a sign of corollary discharge dysfunction, which may potentially cause misattribution of inner speech to external voices.

    View details for Web of Science ID 000171946300022

    View details for PubMedID 11691701

  • Cortical responsiveness during talking and listening in schizophrenia: An event-related brain potential study BIOLOGICAL PSYCHIATRY Ford, J. M., Mathalon, D. H., Kalba, S., Whitfield, S., Faustman, W. O., Roth, W. T. 2001; 50 (7): 540-549


    Failures to recognize inner speech as self-generated may underlie positive symptoms of schizophrenia-like auditory hallucinations. This could result from a faulty comparison in auditory cortex between speech-related corollary discharge and reafferent discharges from thinking or speaking, with misattribution of internal thoughts to external sources. Although compelling, failures to monitor covert speech (thoughts) are not as amenable to investigation as failures to monitor overt speech (talking).Effects of talking on auditory cortex responsiveness were assessed in 10 healthy adults and 12 patients with schizophrenia (DSM-IV) using N1 event-related potentials (ERPs) to acoustic and visual probes during talking aloud, listening to one's speech played back, and silent baseline. Trials contaminated by muscle artifact while talking were excluded.Talking and listening affected N1 to acoustic but not to visual probes, reflecting modality specificity of effects. Patterns of responses to acoustic probes differed between control subjects and patients. N1 to acoustic probes was reduced during talking compared with baseline in control subjects, but not in patients. Listening reduced N1 equivalently in both groups.Although the failure of N1 to be reduced during talking was not related to current hallucinations in patients, it may be related to the potential to hallucinate.

    View details for Web of Science ID 000171582200008

    View details for PubMedID 11600107

  • Respiratory biofeedback-assisted therapy in panic disorder BEHAVIOR MODIFICATION Meuret, A. E., Wilhelm, F. H., Roth, W. T. 2001; 25 (4): 584-605


    The authors describe a new methodologically improved behavioral treatment for panic patients using respiratory biofeedback from a handheld capnometry device. The treatment rationale is based on the assumption that sustained hypocapnia resulting from hyperventilation is a key mechanism in the production and maintenance of panic. The brief 4-week biofeedback therapy is aimed at voluntarily increasing self-monitored end-tidal partial pressure of carbon dioxide (PCO2) and reducing respiratory rate and instability through breathing exercises in patients' environment. Preliminary results from 4 patients indicate that the therapy was successful in reducing panic symptoms and other psychological characteristics associated with panic disorder. Physiological data obtained from home training, 24-hour ambulatory monitoring pretherapy and posttherapy, and laboratory assessment at follow-up indicate that patients started out with low resting PCO2 levels, increased those levels during therapy, and maintained those levels at posttherapy and/or follow-up. Partial dissociation between PCO2 and respiratory rate questions whether respiratory rate should be the main focus of breathing training in panic disorder.

    View details for Web of Science ID 000170514300006

    View details for PubMedID 11530717

  • Respiratory dysregulation in anxiety, functional cardiac, and pain disorders - Assessment, phenomenology, and treatment BEHAVIOR MODIFICATION Wilhelm, F. H., Gevirtz, R., Roth, W. T. 2001; 25 (4): 513-545


    Respiration is a complex physiological system affecting a variety of physical processes that can act as a critical link between mind and body. This review discusses the evidence for dysregulated breathing playing a role in three clinical syndromes: panic disorder, functional cardiac disorder, and chronic pain. Recent technological advances allowing the ambulatory assessment of endtidal partial pressure of CO2 (PCO2) and respiratory patterns have opened up new avenues for investigation and treatment of these disorders. The latest evidence from laboratories indicates that subtle disturbances of breathing, such as tidal volume instability and sighing, contribute to the chronic hypocapnia often found in panic patients. Hypocapnia is also common in functional cardiac and chronic pain disorders, and studies indicate that it mediates some of their symptomatology. Consistent with the role of respiratory dysregulation in these disorders, initial evidence indicates efficacy of respiration-focused treatment.

    View details for Web of Science ID 000170514300003

    View details for PubMedID 11530714

  • Slow recovery from voluntary hyperventilation in panic disorder PSYCHOSOMATIC MEDICINE Wilhelm, F. H., Gerlach, A. L., Roth, W. T. 2001; 63 (4): 638-649


    Because hyperventilation has figured prominently in theories of panic disorder (PD) but not of social phobia (SP), we compared predictions regarding diagnosis-specific differences in psychological and physiological measures before, during, and after voluntary hyperventilation.Physiological responses were recorded in 14 patients with PD, 24 patients with SP, and 24 controls during six cycles of 1-minute of fast breathing alternating with 1 minute of recovery, followed by 3 minutes of fast breathing and 10 minutes of recovery. Speed of fast breathing was paced by a tone modulated at 18 cycles/minute, and depth by feedback aimed at achieving an end-tidal pCO2 of 20 mm Hg. These values were reached equally by all groups.During fast breathing, PD and SP patients reported more anxiety than controls, and their feelings of dyspnea and suffocation increased more from baseline. Skin conductance declined more slowly in PD over the six 1-minute fast breathing periods. At the end of the final 10-minute recovery, PD patients reported more awareness of breathing, dyspnea, and fear of being short of breath, and their pCO2s, heart rates, and skin conductance levels had returned less toward normal levels than in other groups. Their lower pCO2s were associated with a higher frequency of sigh breaths.PD and SP patients report more distress than controls to equal amounts of hypocapnia, but PD differ from SP patients and controls in having slower symptomatic and physiological recovery. This finding was not specifically predicted by hyperventilation, cognitive-behavioral, or suffocation alarm theories of PD.

    View details for Web of Science ID 000170119800015

    View details for PubMedID 11485118

  • The somatic symptom paradox in DSM-IV anxiety disorders: suggestions for a clinical focus in psychophysiology BIOLOGICAL PSYCHOLOGY Wilhelm, F. H., Roth, W. T. 2001; 57 (1-3): 105-140


    Although DSM-IV criteria for anxiety disorders include physiological symptoms, these symptoms are evaluated exclusively by verbal report. The current review explores the background for this paradox and tries to demonstrate on theoretical and empirical grounds how it could be resolved, providing new insights about the role of psychophysiological measures in the clinic. The three-systems approach to evaluating anxiety argues that somatic measures as well as verbal and behavioral ones are indispensable. However, the low concordance between these domains of measurement impugns their reliability and validity. We argue that concordance can be improved by examining the relationship of variables less global than anxiety and by restriction to specific anxiety disorders. For example, recent evidence from our and other laboratories indicate a prominent role of self-reported and physiologically measured breathing irregularities in panic disorder. Nonetheless, even within a diagnosis, anxiety patients vary radically in which somatic variables are deviant. Thus, in clinical practice, individual profiles of psychological and physiological anxiety responses may be essential to indicate distinct therapeutic approaches and ways of tracking improvement. Laboratory provocations specific to certain anxiety disorders and advances in ambulatory monitoring vastly expand the scope of self-report and physiological measurement and will likely contribute to a refined assessment of anxiety disorders.

    View details for Web of Science ID 000170196500006

    View details for PubMedID 11454436

  • Blushing and physiological arousability in social phobia JOURNAL OF ABNORMAL PSYCHOLOGY Gerlach, A. L., Wilhelm, F. H., Gruber, K., Roth, W. T. 2001; 110 (2): 247-258


    Blushing is the most prominent symptom of social phobia, and fear perception of visible anxiety symptoms is an important component of cognitive behavioral models of social phobia. However, it is not clear how physiological and psychological aspects of blushing and other somatic symptoms are linked in this disorder. The authors tested whether social situations trigger different facial blood volume changes (blushing) between social phobic persons with and without primary complaint of blushing and control participants. Thirty social phobic persons. 15 of whom were especially concerned about blushing, and 14 control participants were assessed while watching an embarrassing videotape, holding a conversation, and giving a talk. Only when watching the video did the social phobic persons blush more than controls blushed. Social phobic persons who complained of blushing did not blush more intensely than did social phobic persons without blushing complaints but had higher heart rates, possibly reflecting higher arousability of this subgroup.

    View details for Web of Science ID 000170879900006

    View details for PubMedID 11358019

  • Physiologic instability in panic disorder and generalized anxiety disorder BIOLOGICAL PSYCHIATRY Wilhelm, F. H., Trabert, W., Roth, W. T. 2001; 49 (7): 596-605


    Because panic attacks can be accompanied by surges in physiologic activation, we tested the hypothesis that panic disorder is characterized by fluctuations of physiologic variables in the absence of external triggers.Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Electrodermal, cardiovascular, and respiratory measures were analyzed using complex demodulation to quantify variability in physiologic indices.Both patient groups reported equally more anxiety and cardiac symptoms than control subjects, but certain other somatic symptoms, including breathlessness, were elevated only in panic disorder patients. Mean end-tidal pCO(2) and respiratory rates were lower, and tidal volume and the number of sighs were higher in panic disorder patients than control subjects. Neither cardiovascular (heart rate, arterial pressure, cardiac output), nor electrodermal instability including sighs distinguished the groups; however, tidal volume instability was greater in panic disorder than generalized anxiety disorder patients or control subjects. Several other respiratory measures (pCO(2), respiratory rate, minute volume, duty cycle) showed greater instability in both patient groups than in control subjects.Respiration is particularly unstable in panic disorder, underlining the importance of respiratory physiology in understanding this disorder. Whether our findings represent state or trait characteristics is discussed.

    View details for Web of Science ID 000167899700006

    View details for PubMedID 11297717

  • Characteristics of sighing in panic disorder BIOLOGICAL PSYCHIATRY Wilhelm, F. H., Trabert, W., Roth, W. T. 2001; 49 (7): 606-614


    Sighs, breaths with larger tidal volumes than surrounding breaths, have been reported as being more frequent in patients with anxiety disorders.Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Respiratory volumes and timing were recorded with inductive plethysmography and expired pCO(2), from nasal prongs.Panic disorder patients sighed more and had tonically lower end-tidal pCO(2)s than control subjects, whereas generalized anxiety disorder patients were intermediate. Sighs defined as >2.0 times the subject mean discriminated groups best. Sigh frequency was more predictive of individual pCO(2) levels than was minute volume. Ensemble averaging of respiratory variables for sequences of breaths surrounding sighs showed no evidence that sighs were triggered by increased pCO(2) or reduced tidal volume in any group. Sigh breaths were larger in panic disorder patients than in control subjects. After sighs, pCO(2) and tidal volume did not return to baseline levels as quickly in panic disorder patients as in control subjects.Hypocapnia in panic disorder patients is related to sigh frequency. In none of the groups was sighing a homeostatic response. Panic disorder patients show less peripheral chemoreflex gain than control subjects, which would maintain low pCO(2) levels after sighing.

    View details for Web of Science ID 000167899700007

    View details for PubMedID 11297718

  • Respiratory factors in clinical psychophysiology and biofeedback VERHALTENSTHERAPIE Wilhelm, F. H., Gevirtz, R., Roth, W. T. 2000; 10 (4): 258-271
  • Failures of automatic and strategic processing in schizophrenia: comparisons of event-related brain potential and startle blink modification SCHIZOPHRENIA RESEARCH Ford, J. M., Roth, W. T., Menon, V., Pfefferbaum, A. 1999; 37 (2): 149-163


    Noises elicit startle blinks that are inhibited when immediately (approximately 100 ms) preceded by non-startling prepulses, perhaps reflecting automatic sensory gating. Startle blinks are facilitated when preceded by prepulses at longer lead intervals, perhaps reflecting strategic processes. Event-related brain potentials (ERPs) and startle blinks were used to investigate the well-documented prepulse inhibition failure in schizophrenia. Blinks and ERPs were recorded from 15 schizophrenic men and 20 age-matched controls to noises alone and to noises preceded by prepulses at 120 (PP120), 500 (PP500) and 4000 ms (PP4000) lead intervals. Neither blinks nor any of the ERP components elicited by the noise alone differentiated schizophrenics from controls, although responses to noises were modified by prepulses differently in the two groups. With the N1 component of the ERP, patients showed normal inhibition but lacked facilitation, and with P2, patients lacked inhibition, but showed normal facilitation. With reflex blinks and P300, inhibition was seen in both groups, but no facilitation. These results suggest that different neural circuits are involved in blink and cortical reflections of startle modification in schizophrenics and controls, with both automatic and strategic processes being impaired in schizophrenia.

    View details for Web of Science ID 000080583700003

    View details for PubMedID 10374650

  • Analysis of cardiovascular regulation. Biomedical sciences instrumentation Wilhelm, F. H., Grossman, P., Roth, W. T. 1999; 35: 135-140


    Adequate characterization of hemodynamic and autonomic responses to physical and mental stress can elucidate underlying mechanisms of cardiovascular disease or anxiety disorders. We developed a physiological signal processing system for analysis of continuously recorded ECG, arterial blood pressure (BP), and respiratory signals using the programming language Matlab. Data collection devices are a 16-channel digital, physiological recorder (Vitaport), a finger arterial pressure transducer (Finapres), and a respiratory inductance plethysmograph (Respitrace). Besides the conventional analysis of the physiological channels, power spectral density and transfer functions of respiration, heart rate, and blood pressure variability are used to characterize respiratory sinus arrhythmia (RSA), 0.10-Hz BP oscillatory activity (Mayer-waves), and baroreflex sensitivity. The arterial pressure transducer waveforms permit noninvasive estimation of stroke volume, cardiac output, and systemic vascular resistance. Time trends in spectral composition of indices are assessed using complex demodulation. Transient dynamic changes of cardiovascular parameters at the onset of stress and recovery periods are quantified using a regression breakpoint model that optimizes piecewise linear curve fitting. Approximate entropy (ApEn) is computed to quantify the degree of chaos in heartbeat dynamics. Using our signal processing system we found distinct response patterns in subgroups of patients with coronary artery disease or anxiety disorders, which were related to specific pharmacological and behavioral factors.

    View details for PubMedID 11143335

  • Voluntary breath holding in panic and generalized anxiety disorders PSYCHOSOMATIC MEDICINE Roth, W. T., Wilhelm, F. H., Trabert, W. 1998; 60 (6): 671-679


    Because breath holding causes arterial pCO2 to increase, we used it to test the hypothesis that in panic disorder (PD) a biological suffocation monitor is pathologically sensitive.Nineteen patients with PD, 17 with generalized anxiety disorder (GAD), and 22 normal controls took deep breaths on signal and held them until a release signal was given 30 seconds later. This was repeated 12 times separated by 60-second normal breathing periods.PD patients reported having had in the past more symptoms of shortness of breath when anxious, and more frequent frightening suffocation experiences than the other groups. However, increases in self-rated anxiety between periods of normal breathing and periods of breath holding were similar in all three groups. Skin conductance, blood pressure, and T-wave amplitude reactions to breath holdings were also similar, but heart rate acceleration upon taking a deep breath was greater in GAD patients. Before and after individual breath holdings, end-tidal pCO2 was lower in PD patients than in normal controls; GAD patients were intermediate. Inspiratory flow rate did not differ between groups.Our physiological results provide no direct support for an overly sensitive suffocation alarm system in PD. Lower pCO2 may be due to anxiety causing hyperventilation in patients prone to panic.

    View details for Web of Science ID 000077189300003

    View details for PubMedID 9847025

  • Using minute ventilation for ambulatory estimation of additional heart rate BIOLOGICAL PSYCHOLOGY Wilhelm, F. H., Roth, W. T. 1998; 49 (1-2): 137-150


    Both physical activity and emotion produce physiological activation. The emotional component of heart rate (HR) can be estimated as the additional HR (aHR) above that predicted by O2 consumption. Our innovation was to substitute minute ventilation (V) for O2 consumption, calculating aHR from individual relations between V and HR during an exercise test. We physiologically monitored 28 flight phobics and 15 non-anxious controls while walking (leaving the hospital, entering a plane), and during a commercial flight. Raw HR did not differ between phobics and controls when leaving the hospital (118/114 bpm) or entering the plane (117/110 bpm). However, although aHR was not different when leaving the hospital (7.0/8.6 bpm), it was significantly greater when entering the plane (17.5/9.9 bpm), accurately reflecting the increased subjective anxiety of the phobics. V was not higher in phobics than controls during any condition, suggesting an absence of hyperventilation in the phobics. The results demonstrate the utility of our method for analyzing HR in people whose stress occurs when they are physically active.

    View details for Web of Science ID 000076545300010

    View details for PubMedID 9792490

  • Taking the laboratory to the skies: Ambulatory assessment of self-report, autonomic, and respiratory responses in flying phobia PSYCHOPHYSIOLOGY Wilhelm, F. H., Roth, W. T. 1998; 35 (5): 596-606


    We evaluated the feasibility of recording multiple physiological anxiety measures during a flight and how well they could distinguish flight phobics from controls. Benefits of baseline adjustment and transformation for all variables and adjustment of heart rate by ventilation to give additional heart rate were calculated. Effect size, one measure of the power to discriminate groups, was between 1.1 and 1.7 for heart rate measures. Although respiratory rate and minute ventilation, indicators of hyperventilation, did not differ between groups, phobics paused more during inspiration than did controls. Phobics also showed more skin conductance fluctuations and less respiratory sinus arrhythmia. Self-reported anxiety was a more powerful discriminator than physiological measures, a result that may be partially explained by how phobics were selected. These results indicate that monitoring of multiple physiological systems outside the laboratory is practical and informative. Physiological measures of psychological importance can be quantified accurately in a noisy, changing, unsupervised ambulatory setting.

    View details for Web of Science ID 000075303100012

    View details for PubMedID 9715103

  • Critique - Trusting computerized data reduction too much: A critique of Anderson's ambulatory respiratory monitor BIOLOGICAL PSYCHOLOGY Wilhelm, F. H., Roth, W. T. 1998; 49 (1-2): 215-219

    View details for Web of Science ID 000076545300014

    View details for PubMedID 9792494

  • Autonomic instability during relaxation in panic disorder PSYCHIATRY RESEARCH Roth, W. T., Wilhelm, F. H., Trabert, W. 1998; 80 (2): 155-164


    The ability to relax was assessed in 14 patients with panic disorder (PD) and 15 non-anxious control subjects for 10 min. Before and after relaxation, subjects performed a standardized activating task of talking continuously for 4 min. The fractional decline in reported anxiety, tension, and alertness between the first talking period and the relaxation minimum did not differ between groups, although absolute levels of anxiety and tension were higher for PD patients. The fractional decline in skin conductance between the first talking period and the last minute of relaxation was less for PD patients than control subjects, while their increase in skin temperature was greater. Skin conductance showed a linear decline over the logarithm of relaxation time, the slope of which was less steep for PD patients. Goodness of fit of skin conductance over log time was also significantly poorer for PD patients. Heart rate levels or slopes did not differ between groups. Autonomic differences between PD and control subjects were largely due to six patients who reported having panic attacks during the test and higher pretest anxiety levels. In conclusion, indicators of relaxation were inconsistent. Skin conductance suggested autonomic instability during quiet sitting in patients who panic or who are prone to panic.

    View details for Web of Science ID 000075876300007

    View details for PubMedID 9754695

  • Personality, psychological states and heart rate in novice and expert parachutists PERSONALITY AND INDIVIDUAL DIFFERENCES Breivik, G., Roth, W. T., Jorgensen, P. E. 1998; 25 (2): 365-380
  • Acute and delayed effects of alprazolam on flight phobics during exposure VERHALTENSTHERAPIE Wilhelm, F. H., Roth, W. T. 1998; 8 (1): 38-47
  • Speech disturbances and gaze behavior during public speaking in subtypes of social phobia JOURNAL OF ANXIETY DISORDERS Hofmann, S. G., Gerlach, A. L., Wender, A., Roth, W. T. 1997; 11 (6): 573-585


    Twenty-four social phobics with public speaking anxiety and 25 nonphobic individuals (controls) gave a speech in front of two people. Subjective anxiety, gaze behavior, and speech disturbances were assessed. Based on subjects' fear ratings of social situations, phobics and controls were divided into the generalized and nongeneralized subtype. Results showed that generalized phobics reported the most, and nongeneralized controls the least anxiety during public speaking. All subjects had longer and more frequent eye contact when delivering a speech than when talking with an experimenter or sitting in front of an audience. Phobics showed more filled pauses, had longer silent pauses, paused more frequently, and spent more time pausing than controls when giving a speech. Generalized phobics spent more time pausing during their speech than the other subgroups (nongeneralized controls, generalized controls, and nongeneralized phobics). These results suggest that generalized phobics tended to shift attentional resources from speech production to other cognitive tasks.

    View details for Web of Science ID 000071540800002

    View details for PubMedID 9455720

  • Acute and delayed effects of alprazolam on flight phobics during exposure BEHAVIOUR RESEARCH AND THERAPY Wilhelm, F. H., Roth, W. T. 1997; 35 (9): 831-841


    In order to test if a benzodiazepine would enhance or hinder the therapeutic effects of exposure, immediate and delayed effects of alprazolam on flight phobics were assessed by questionnaires and ambulatory physiological recording. Physiological measures included heart rate, skin conductance level and fluctuations, finger temperature, respiratory sinus arrhythmia, and various respiratory measures derived from two bands calibrated for each subject. Twenty-eight women with flying phobia flew twice at a 1-week interval. One and a half hours before flight 1, 14 randomly assigned phobics received double-blind 1 mg of alprazolam and 14 received placebo. On flight 1, alprazolam reduced self-reported anxiety (5.0 vs 7.4) and symptoms (5.3 vs 3.6) more than placebo, but induced an increase in heart rate (114 vs 105 bpm) and respiratory rate (22.7 vs 18.3 breaths/min). Before flight 2, the alprazolam group did not expect to be more anxious than the placebo group (6.7 vs 6.5), but in fact indicated more anxiety during flight (8.5 vs 5.6), and a substantial increase in panic attacks from flight 1 to flight 2 (7% vs 71%). Heart rates in the alprazolam group increased further (123 bpm). Results indicate that alprazolam increases physiological activation under acute stress conditions and hinders therapeutic effects of exposure in flying phobia.

    View details for Web of Science ID A1997XR87500005

    View details for PubMedID 9299803

  • Clinical characteristics of flight phobia JOURNAL OF ANXIETY DISORDERS Wilhelm, F. H., Roth, W. T. 1997; 11 (3): 241-261


    Sixty-six subjects with severe fear of flying were recruited by advertisement and compared to 21 controls without flying fears. Subjects were interviewed and given several questionnaires to determine DSM-III-R diagnoses, history of flying, and development and course of flying phobia. Our phobic sample had a mean age of 46 and was 89% female. Diagnostically, 27% met criteria for current Panic Disorder with Agoraphobia, and 17% criteria for that diagnosis in the past. These two groups were more concerned with internal or social anxiety stimuli during flight than the group who had never had panic attacks but met criteria for Simple Phobia (flying). All three groups were equally concerned about external dangers. Traumatic flight events were common in phobics and controls, but phobics reported reacting to these events more strongly. Our results suggest a vulnerability-stress model with several vulnerability factors, including cognitive ones. Treatment implications are discussed.

    View details for Web of Science ID A1997XG50100002

    View details for PubMedID 9220299

  • N400 evidence of abnormal responses to speech in Alzheimer's disease ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Ford, J. M., Woodward, S. H., SULLIVAN, E. V., Isaacks, B. G., Tinklenberg, J. R., Yesavage, J. A., Roth, W. T. 1996; 99 (3): 235-246


    The status of semantic priming in Alzheimer's disease (AD) was examined using the speech elicited N400 component of the event-related brain potential (ERP). Speech was naturally paced, with 1 s of silence before the final word. In the semantic task, subjects attended to the meaning of the sentences for a subsequent memory test. In the phonemic monitoring task, they counted the words beginning with the letter 'p'. The effects of age were assessed by comparing young and elderly, and the effects of disease by comparing elderly and AD subjects. In healthy young and elderly subjects, N400s were large to semantically unprimed words and small to semantically primed words. In AD subjects, N400s were large to primed words, reflecting a failure of the sentence stem to prime the final word, and probably an impairment in semantic knowledge. The N400 priming effect was not smaller during the phonemic than semantic task in any group, suggesting that the semantic qualities of speech are processed even when subjects are attending to phonemic qualities. N400 latency was delayed with age and further delayed with dementia.

    View details for Web of Science ID A1996VL66900004

    View details for PubMedID 8862113

  • Activation in novice and expert parachutists while jumping PSYCHOPHYSIOLOGY Roth, W. T., Breivik, G., Jorgensen, P. E., Hofmann, S. 1996; 33 (1): 63-72


    Heart and respiration rates were measured ambulatorily in 16 novice and 25 expert (> 380 delayed free-fall jumps) sports parachutists while making a static-line jump. Self-reported anxiety and heart rate peaked near the point of jumping in both groups rather than earlier in experts, as reported by Fenz and Epstein (1967, Psychosomatic Medicine, 29, 33-51). While sitting in the airplane 1 min before exit, mean heart rate was 124 bpm in novices and 102 in experts and increased during jumping to 170 and 145, respectively. The almost identical rise in the two groups could be accounted for largely by physical exertion, replicated with jumps from a training model on the ground. Exercise testing at a different location showed that experts were more fit. Respiration rate was higher in the airplane than at baselines, especially for novices. In conclusion, our results are more compatible theoretically with extinction of anticipatory anxiety than with learned anxiety inhibition.

    View details for Web of Science ID A1996TM04800007

    View details for PubMedID 8570796



    Individuals meeting criteria of the revised third edition of Diagnostic and Statistical Manual for Mental Disorders (American Psychiatric Association, 1987) for social phobia with a fear of speaking in front of people were subdivided into those with (n = 16) and without (n = 14) avoidant personality disorder (APD). These individuals and nonanxious controls (n = 22) spoke in front of a small audience while speaking time, subjective anxiety, fearful thoughts, and electrocardiographic and respiratory measures were recorded. Controls spoke for longer than either social phobia group. Those with social phobia and APD reported more subjective anxiety and more fear cognitions than the other two groups; phobic individuals without APD showed greater heart rates in the phobic situation than either social phobics with APD or controls. The latter two groups did not differ in heart rate. These results indicate incongruent subjective and heart rate responses to the feared situation. A similar pattern of results was found when participants were divided into generalized and specific social phobia groups.

    View details for Web of Science ID A1995QD42800025

    View details for PubMedID 7897046

  • ERPS IN SCHIZOPHRENIA - EFFECTS OF ANTIPSYCHOTIC MEDICATION BIOLOGICAL PSYCHIATRY Ford, J. M., White, P. M., Csernansky, J. G., Faustman, W. O., Roth, W. T., Pfefferbaum, A. 1994; 36 (3): 153-170


    Thirty unmedicated schizophrenics were compared to 29 age-matched controls on auditory and visual event-related brain potential (ERP) paradigms. Twenty-one of these patients were tested again after 1 week on placebo and after 4 weeks on antipsychotic medication. Before treatment, N1, N2, and P3 components of the auditory ERP were smaller in the schizophrenics than in the controls. Although visual N2 was smaller in schizophrenics, visual P3 was not. In spite of significant clinical improvement with antipsychotic treatment, amplitudes of auditory and visual N1, N2, and P3 were not significantly changed. Higher blood levels of antipsychotic medication were related to reductions in auditory P3 latency, however. In addition, higher levels of cerebrospinal fluid (CSF) MHPG (methoxyhydroxyphenylglycol) were associated with larger auditory N1s and larger auditory and visual P3s, suggesting an influence of arousal on these components in schizophrenics. In spite of this influence, reduction of the auditory P3 in schizophrenia is an enduring trait of the disease, which is not affected by antipsychotic medication or clinical improvement.

    View details for Web of Science ID A1994PB80100003

    View details for PubMedID 7948453

  • DOES BEHAVIORAL TREATMENT OF SOCIAL PHOBIA LEAD TO COGNITIVE CHANGES BEHAVIOR THERAPY Newman, M. G., Hofmann, S. G., Trabert, W., Roth, W. T., Taylor, C. B. 1994; 25 (3): 503-517

    View details for Web of Science ID A1992KA26000031

    View details for PubMedID 1435914

  • P3 AND SCHIZOPHRENIA ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Ford, J. M., Pfefferbaum, A., Roth, W. 1992; 658: 146-162

    View details for Web of Science ID A1992JL81200010

    View details for PubMedID 1353949

  • STRESS TEST REACTIVITY IN PANIC DISORDER ARCHIVES OF GENERAL PSYCHIATRY Roth, W. T., MARGRAF, J., Ehlers, A., Taylor, C. B., Maddock, R. J., Davies, S., Agras, W. S. 1992; 49 (4): 301-310


    The psychological and physiological reactivity of 52 patients with panic disorder to mental arithmetic, cold pressor, and 5% carbon dioxide inhalation tests was compared with that of 26 age- and sex-matched normal subjects. In general, patients with panic disorder were neither more physiologically reactive to these stressors than normal subjects nor slower to recover from them, but they were tonically more anxious and much more likely to ask to stop carbon dioxide inhalation or to report panic attacks during this test. Patients who reported panic attacks (46%) had manifested greater anticipatory anxiety before the gas was delivered, accompanied with increased beta-adrenergic cardiac tone. Thus, anticipatory anxiety can be an important factor in panic provocation. Physiological measures varied greatly in their sensitivity to phasic or tonic anxiety. Carbon dioxide stimulated large increases in respiratory minute volume, but these increases were no greater for patients than for normal subjects.

    View details for Web of Science ID A1992HM91400006

    View details for PubMedID 1558464



    The reactivity of 40 panic disorder patients on mental arithmetic, cold pressor, and 5% CO2 inhalation stressors was tested before and after 8 weeks of treatment with imipramine, alprazolam, or placebo. Mean levels of subjective and physiological stress measures were compared during a baseline before any stressors were given, and at anticipation, stressor, and recovery periods for each stressor. After treatment, imipramine patients differed from the other two treatment groups on the prestressor baseline in showing higher systolic blood pressure (mean difference about 10 mmHg), higher diastolic blood pressure (10 mm Hg), higher heart rate (15 bpm), less respiratory sinus arrhythmia, shorter pulse transit time, and lower T-wave amplitude. Respiratory measures, electrodermal measures, body movement, and self-reported anxiety and excitement did not distinguish the groups. Reactivity to the stress tests was unaffected by the medications, but tonic differences present in the baseline persisted.

    View details for Web of Science ID A1992GX47400004

    View details for PubMedID 1543796

  • IS THERE P300 ASYMMETRY IN SCHIZOPHRENIA - REPLY ARCHIVES OF GENERAL PSYCHIATRY Pfefferbaum, A., Ford, J. M., White, P. M., Roth, W. T., Mathalon, D. H. 1991; 48 (4): 381-383


    Event-related potentials (ERPs) and electrodermal activity were studied in 14 medicated schizophrenics, 17 unmedicated schizophrenics, and 23 age- and education-matched controls. Subjects were run in three auditory stimulus paradigms differing from the usual ERP paradigms in having interstimulus intervals greater than 12 sec to permit measurement of the longer latency skin conductance response (SCR). In every paradigm medicated but not unmedicated schizophrenics had smaller N120 amplitudes and fewer SCRs than controls. In addition, medicated schizophrenics showed reduced P200 amplitude and latency, longer P320 latency, and reduced skin conductance levels in certain paradigms. These effects cannot easily be attributed to different mental states of medicated and unmedicated patients, since their Brief Psychiatric Rating Scale scores were almost the same. It is more probable that antipsychotic and antiparkinsonian drugs reduced electrodermal activity through anticholinergic mechanisms and that the antipsychotic drugs attenuated N120 through other biological mechanisms.

    View details for Web of Science ID A1991FG08800007

    View details for PubMedID 1675890

  • HOW BLIND ARE DOUBLE-BLIND STUDIES JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY MARGRAF, J., Ehlers, A., Roth, W. T., Clark, D. B., Sheikh, J., Agras, W. S., Taylor, C. B. 1991; 59 (1): 184-187


    Psychopharmacological studies usually attempt to eliminate "nonspecific" influences on outcome by double-blind designs. In a randomized, double-blind comparison of alprazolam, imipramine, and placebo, the great majority of panic disorder patients (N = 59) and their physicians were able to rate accurately whether active drug or placebo had been given. Moreover, physicians could distinguish between the two types of active drugs. Inasmuch as correct rating was possible halfway through treatment, concerns about the internal validity of the double-blind strategy arise.

    View details for Web of Science ID A1991EV98700024

    View details for PubMedID 2002136

  • FILTER FREQUENCY IN P-3 EXPERIMENTS BIOLOGICAL PSYCHIATRY Pfefferbaum, A., Ford, J. M., Roth, W. T. 1990; 28 (12): 1070-1071

    View details for Web of Science ID A1990EP89400012

    View details for PubMedID 2289003



    Skin conductance habituation was compared between 38 patients meeting DSM-III criteria for Panic Disorder and 29 normal controls. Approximately half of each group was randomly assigned to be given 100 dB SPL tones and the other half 75 dB tones. All indices pointed to slowed habituation in patients compared with normals: number of trials to response habituation, total number of responses, and slope of decline of skin conductance level. Patient-normal differences were not significantly larger for 100 dB than for 75 dB. In addition, patients compared with normals had more nonspecific fluctuations, higher skin conductance levels, and a shorter response latency to the first stimulus. Stepwise discriminant analyses classified patients and normals better in the 100 dB than in the 75 dB condition, and showed that the various skin conductancy variables were largely redundant at the higher intensity.

    View details for Web of Science ID A1990DF72900007

    View details for PubMedID 2191728



    Seventy-nine patients with panic disorder were randomized to an 8-week double-blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure.

    View details for Web of Science ID A1990CX84900006

    View details for PubMedID 2187912

  • MOTOR-ACTIVITY AND TONIC HEART-RATE IN PANIC DISORDER PSYCHIATRY RESEARCH Clark, D. B., Taylor, C. B., Hayward, C., King, R., MARGRAF, J., Ehlers, A., Roth, W. T., Agras, W. S. 1990; 32 (1): 45-53


    Motor activity and tonic heart rate were monitored in 62 drug-free panic disorder patients and 40 normal control subjects. Mean daily activity, mean waking heart rate controlled for activity, and mean sleeping heart rate were determined. Panic disorder patients without phobic avoidance showed higher activity than control subjects or patients with limited or extensive avoidance. Similarly, an "inverted U", relationship between trait anxiety and activity was observed. On the other hand, neither mean waking nor sleeping heart rate showed significant differences between patients and controls, suggesting that the differences previously reported in laboratory studies result from anticipatory anxiety.

    View details for Web of Science ID A1990DC99700006

    View details for PubMedID 2349312

  • SURREPTITIOUS DRUG-USE BY PATIENTS IN A PANIC DISORDER STUDY AMERICAN JOURNAL OF PSYCHIATRY Clark, D. B., Taylor, C. B., Roth, W. T., Hayward, C., Ehlers, A., MARGRAF, J., Agras, W. S. 1990; 147 (4): 507-509


    In a double-blind, placebo-controlled trial comparing alprazolam and imipramine for panic disorder, serum analysis revealed that a substantial proportion of the patients took explicitly prohibited anxiolytic medication. Excluding these patients changed the results.

    View details for Web of Science ID A1990CW81000023

    View details for PubMedID 1969248



    The Fear and Avoidance Scales (FAS) is an 11-item questionnaire consisting of two subscales that measure features of agoraphobia and claustrophobia and that were demonstrated to be valid Guttman scales in a British clinical population. The purposes of the study reported here were to replicate the scale characteristics in the United States and to determine if improvement during treatment would follow the sequence predicted by the hierarchy implied in the scales. The FAS was given to 25 female agoraphobics before and after behavioural treatment. A principal components analysis replicated the agoraphobia and claustrophobia factors established in the British sample. Scalogram analyses showed that the Claustrophobia subscale of the FAS was a valid Guttman scale in the US sample whereas the Agoraphobia subscale yielded a high coefficient of reproducibility but a low coefficient of scalability. Treatment reduced the patients' fears and avoidances in the predicted sequence since for both scales the hierarchy of items remained unchanged following treatment.

    View details for Web of Science ID A1990CP17400004

    View details for PubMedID 2310869



    A survey of 794 subjects volunteering for studies of panic disorder with or without phobic avoidance revealed that fewer than 15% had received imipramine and fewer than 15% had undergone in vivo exposure, although the majority had engaged in some form of counseling and had used benzodiazepines. Subjects with spontaneous panic attacks reported more avoidance than subjects with situational attacks. One-half of the subjects were unemployed. The authors recommend wider use of the available effective treatments for panic disorder and phobic avoidance.

    View details for Web of Science ID A1989AX18500005

    View details for PubMedID 2817112



    Eighteen schizophrenics who were not taking medication, 13 schizophrenics who were taking medication, and 37 age-matched controls were tested with event-related potential paradigms designed to elicit P3 response automatically or effortfully (ie, with a choice reaction time task). Electroencephalograms were recorded from the 19 standard 10-20 electrode sites. Compared with controls, both groups of schizophrenics had reduced P3 amplitudes for both effortful and automatic paradigms. P3 latencies were delayed relative to controls for the medication-taking schizophrenics in the effortful paradigms. Negative symptoms derived from the Brief Psychiatric Rating Scale within 1 week of event-related potential testing correlated negatively with both auditory and visual P3 amplitude in the subjects who were not taking medication. There was no evidence that P3 is smaller over left temporal electrode sites in schizophrenics, as has been reported by others. P3 amplitude reduction in schizophrenia is a robust psychobiological phenomenon that is present regardless of medication status or task demands.

    View details for Web of Science ID A1989AY08200009

    View details for PubMedID 2573328



    Plasma lipids were measured in 102 subjects with panic disorder or agoraphobia. In women, but not men, a significantly higher than expected number of subjects had cholesterol values that exceeded the 75th percentile of national reference values for their sex and age.

    View details for Web of Science ID A1989AD14300020

    View details for PubMedID 2742017



    Twenty patients with panic attacks and ten controls were given a standardised interview about thoughts occurring during times of anxiety or panic attacks. The interviewer was blind to the subject's diagnosis. The 20 panic patients underwent a psychophysiological test battery which included a cold pressor test, mental arithmetic task, and 5.5% CO2 inhalation. More patients than controls reported thoughts centered on fears of losing control and shame when anxious. Panic patients rated their thoughts as stronger and clearer than did controls and they had more difficulty excluding them from their minds. A feeling of anxiety preceded anxious thoughts in patients. This suggests that 'faulty cognitions' are not the initial event in a panic attack, although anxious thoughts may exacerbate or maintain them. Significant correlations were found between the intensity of anxiety-related thoughts in anticipation of mental arithmetic and changes in diastolic blood pressure and heart rate during mental arithmetic.

    View details for Web of Science ID A1989AJ61700013

    View details for PubMedID 2605437


    View details for Web of Science ID A1988N733300001

    View details for PubMedID 3406326


    View details for Web of Science ID A1988N733300002

    View details for PubMedID 3406327



    Twenty-three patients meeting DSM-III criteria for agoraphobia with panic attacks and 14 age-, race-, and sex-matched nonanxious controls were tested in the laboratory and on a test walk in a shopping mall. The patients were tested before and after about 15 weeks of treatment with placebo and exposure therapy, imipramine and exposure therapy, or imipramine and initial antiexposure instructions. Controls were tested twice at a similar interval, but without any treatment. On test day 1, patients compared to controls showed higher average heart rate and skin conductance levels and greater numbers of skin conductance fluctuations in the laboratory, and higher heart rates before and during the test walk. Between pretreatment and posttreatment tests, clinical ratings improved and skin conductance levels decreased in all treatment groups. Heart rate levels in the laboratory, on the other hand, decreased in patients on placebo and rose in patients on imipramine. Thus, imipramine compromises the usefulness of heart rate as a measure of emotional arousal. Higher pretreatment heart rates predicted greater clinical improvement.

    View details for Web of Science ID A1988N420300012

    View details for PubMedID 3393620



    There has been considerable speculation about a possible relationship between panic disorder and mitral valve prolapse syndrome (MVP), although empirical results have been highly inconsistent. Some studies report low frequencies of 0-8%, others high frequencies of 24-35% "definite" MVP in panic patients (average across 17 studies: 18% of panic patients, 1% of normal controls). Elevated prevalences of MVP were also reported for generalized anxiety disorder, bipolar affective disorder, and anorexia nervosa. Studies of MVP patients generally failed to find elevated prevalence of panic compared to other cardiac patients or normal controls (averages across seven studies: 14%, 10%, and 8%, respectively). Inconsistent results may be due to widely different diagnostic criteria for MVP, low reliability of this diagnosis, inadequate control groups, "non-blind" ratings of panic or MVP, and sampling bias in both patient and control populations. These problems as well as the great variations in the published results preclude any final judgment. If there is concomitance between MVP and panic, it is small and primarily involves subjects with milder or reversible variants of MVP. At present it seems most justified, however, to assume co-morbidity in highly symptomatic individuals rather than a functional relationship.

    View details for Web of Science ID A1988M721400001

    View details for PubMedID 3287421


    View details for Web of Science ID A1988L510500001

    View details for PubMedID 3341996

  • Selective Processing of Threat Cues in Subjects with Panic Attacks COGNITION & EMOTION Ehlers, A., Margraf, J., Davies, S., Roth, W. T. 1988; 2 (3): 201-219
  • Treadmill exercise test and ambulatory measures in panic attacks. American journal of cardiology Taylor, C. B., King, R., Ehlers, A., MARGRAF, J., Clark, D., Hayward, C., Roth, W. T., Agras, S. 1987; 60 (18): 48J-52J


    Treadmill exercise test performance and ambulatory heart rate and activity patterns of 40 patients with panic attacks were compared with 20 age-matched controls (control group 1) and 20 nonexercising controls (control group 2). All patients underwent a symptom-limited exercise stress test. Panic attack patients and control group 1 wore an ambulatory heart rate/activity monitor for up to 3 days. Panic patients had a significantly higher heart rate at 4 and 6 METS than either control group. The max METS were 11.2 +/- 2.3, 13.5 +/- 2.3 and 11.2 +/- 1.8 for the panic attack patients and control groups 1 and 2, respectively. One panic patient had ischemia on the treadmill at 12 METS. Panic patients had a significantly higher standing heart rate than controls. Furthermore, 11 of 39 panic patients had tachycardia on standing compared with 3 of 40 controls. Panic attack patients had higher wake and sleep heart rates than control group 1, but the differences were not significant. These results are consistent with autonomic dysfunction in panic patients but may also be due to differences in physical conditioning. The treadmill can be useful for reassuring patients and for identifying the rare patient with ischemia on exercise.

    View details for PubMedID 3425557



    Despite much recent research, there is still little systematic information about the phenomenology of panic attacks, and their possible causes remain obscure. We investigated panic attacks in the natural environment using an event sampling approach. Twenty-seven panic attack patients and 19 matched normal controls kept panic attack and self-exposure diaries for 6 days and wore an ambulatory heart rate/physical activity recorder for 3 days. Patients reported 175 attacks, generally of moderate severity. The most frequent symptoms were palpitations, dizziness/lightheadedness, dyspnea, nausea, sweating, and chest pain/discomfort. The results did not support the classification of panic attacks recently proposed by Sheehan and Sheehan, which requires three symptoms as a cutoff for panic attacks. Panic attacks classified by the patients as situational (i.e., occurring in feared situations) were more severe and occurred in situational contexts different from spontaneous attacks, but were otherwise phenomenologically similar. Heart rates did not change during spontaneous attacks and were only mildly elevated during situational attacks or during the 15 minutes preceding these attacks. These heart rate changes were interpretable as effects of anxiety, although physical activity showed a similar pattern of changes. Some normal control subjects reported on the panic diary primarily situational anxiety episodes that were phenomenologically similar to, albeit less severe than, the patients' episodes. Panic patients may sometimes fail to perceive environmental triggers for their attacks because many attacks classified as spontaneous occurred in classical "phobic" situations. Furthermore, the comparison of concurrent diary and retrospective interview and questionnaire descriptions showed that panic patients have a tendency toward retrospective exaggeration. Implications for the assessment, definition, and classification of panic attacks are discussed.

    View details for Web of Science ID A1987K221300008

    View details for PubMedID 3655782

  • Event-related potentials to deviations of pitch and of timing. Electroencephalography and clinical neurophysiology. Supplement Nordby, H., Roth, W. T., Pfefferbaum, A. 1987; 40: 241-245

    View details for PubMedID 3480129

  • AUTONOMIC CHARACTERISTICS OF AGORAPHOBIA WITH PANIC ATTACKS BIOLOGICAL PSYCHIATRY Roth, W. T., Telch, M. J., Taylor, C. B., SACHITANO, J. A., Gallen, C. C., KOPELL, M. L., MCCLENAHAN, K. L., Agras, W. S., Pfefferbaum, A. 1986; 21 (12): 1133-1154


    We compared electrodermal and heart rate measures of autonomic activation between patients meeting DSM-III criteria for agoraphobia with panic attacks and controls in terms of tonic level, reactivity to various types of stimuli, recovery, habituation, and spontaneous variability. The most striking differences between groups in the laboratory were higher tonic levels of skin conductance and heart rate among patients. Patients' heart rates were also tonically elevated in a test situation outside the laboratory. Certain measures of habituation and spontaneous variability also differed between groups, but there were only weak and inconsistent differences in reactivity to, or recovery from, stimuli with diverse qualities of novelty, startlingness, intensity, or phobicity. The elevated activation levels may be signs of a chronic state or may be phobic responses to the testing situations. A minority of patients failed to show these elevated levels.

    View details for Web of Science ID A1986D850400004

    View details for PubMedID 3756263



    Ten patients with panic disorder or agoraphobia with panic attacks and 10 normal controls received infusions of normal saline (placebo) and sodium lactate in a single-blind design. The time course of changes in the dependent variables was closely monitored, and expectancy biases and demand characteristics were minimized. Lactate increased self-reported anxiety and heart rate equally in patients and controls. The only variables showing statistically different responses between the groups were systolic and diastolic blood pressure. Overall, in both groups, the effects of lactate were quite similar to states of natural panic or anxiety for both self-report measures and heart rate. Patients had a tendency to endorse somatic symptoms indiscriminately. Our data do not support response to lactate as a biological marker of proneness to panic attacks.

    View details for Web of Science ID A1986C200600006

    View details for PubMedID 3714912

  • AMBULATORY HEART-RATE CHANGES IN PATIENTS WITH PANIC ATTACKS AMERICAN JOURNAL OF PSYCHIATRY Taylor, C. B., Sheikh, J., Agras, W. S., Roth, W. T., MARGRAF, J., Ehlers, A., Maddock, R. J., Gossard, D. 1986; 143 (4): 478-482


    Of 33 "panic" attacks reported by patients wearing an ambulatory solid-state heart rate/activity monitor for 6 days, 19 (58%) occurred at heart rates disproportionate to activity levels and different enough from surrounding heart rates to indicate a distinct physiologic state. Intense panic attacks with three or more symptoms were the most readily identified. ECG monitoring found the elevated heart rates to be sinus tachycardias. Heart rate elevation did not occur during anticipatory anxiety episodes. Ambulatory heart rate recordings confirm the presence of major physiologic changes during self-reported panic attacks.

    View details for Web of Science ID A1986A725500010

    View details for PubMedID 3953890

  • Applications of cognitive ERPs in psychiatric patients. Electroencephalography and clinical neurophysiology. Supplement Roth, W. T., Duncan, C. C., Pfefferbaum, A., Timsit-Berthier, M. 1986; 38: 419-438

    View details for PubMedID 3466780


    View details for Web of Science ID A1986D906000008

    View details for PubMedID 3753383



    Response to sodium lactate infusions has been proposed as an experimental model and a biologic marker for panic attacks. Several authors have claimed that patients suffering from panic attacks, but not normal controls, "panic" in response to lactate. A careful review of methods and results of 13 studies, however, reveals serious methodologic problems, lack of specificity and sensitivity, and a failure to consider cognitive variables. When baseline differences are ruled out, the responses of patients and controls may not differ. So far, response to lactate cannot be interpreted as a model and marker for panic attacks and does not provide evidence for their underlying biologic distinctness from other types of anxiety. Known biologic mechanisms do not sufficiently explain the effects of lactate. Instead, an interaction of peripheral physiologic changes, past experience, environmental cues, and their appraisal as threatening or dangerous seems to be a more appropriate model.

    View details for Web of Science ID A1986AYV7400002

    View details for PubMedID 3511491


    View details for Web of Science ID A1985AHA9400011

    View details for PubMedID 2860892



    Patients with dementia, schizophrenia and depression were tested with analogous auditory and visual event-related potential (ERP) paradigms designed to elicit a large P3. The patient groups were compared to age normative predictions derived from a large control sample for a number of ERP and behavioral variables. The results were similar for the auditory and visual paradigms. P3 latency was prolonged two or more S.D.s beyond that predicted by age for less than one-half of the demented patients. This latency prolongation was significant for the group as a whole but would result in too many false negatives if used diagnostically for individuals. Furthermore, increased P3 latency was not specific, as the schizophrenic patients also had later P3s. The amplitude of P3 was reduced in the demented patients, but it was also smaller in other patient groups. The only variable which distinguished the demented patients from both controls and from the other patients was the single trial P3 latency/RT correlation. The demented patients, as a group, had significantly lower P3 latency/RT correlations, but this effect also was not sensitive enough to be diagnostic for individuals. The data from these two paradigms suggest that the P3 amplitude and latency abnormalities observed reflect a common, rather than a diagnostically specific deficit. This study is in contrast to some others which report much more sensitivity and specificity in the use of P3 latency in the diagnosis of dementia. Differences in task demands, patient samples and ERP analysis techniques might explain some of the discrepancy.

    View details for Web of Science ID A1984SN71300002

    View details for PubMedID 6200305

  • ERPS AND PSYCHOPATHOLOGY .1. BEHAVIORAL PROCESS ISSUES ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Roth, W. T., Tecce, J. J., Pfefferbaum, A., Rosenbloom, M., Callaway, E. 1984; 425 (JUN): 496-522


    The clinical study of ERPs has an inherent defect--a self-selection of clinical populations that hampers equating of clinically defined groups on factors extraneous to the independent variables. Such ex post facto studies increase the likelihood of confounding variables in the interpretation of findings. Hence, the development of lawful relationships between clinical variables and ERPs is impeded and the fulfillment of description, explanation, prediction, and control in brain science is thwarted. Proper methodologies and theory development can increase the likelihood of establishing these lawful relationships. One methodology of potential value in the clinical application of ERPs, particularly in studies of aging, is that of divided attention. Two promising theoretical developments in the understanding of brain functioning and aging are the distraction-arousal hypothesis and the controlled-automatic attention model. The evaluation of ERPs in the study of brain-behavior relations in clinical populations might be facilitated by the differentiation of concurrent, predictive, content, and construct validities.

    View details for Web of Science ID A1984TA47400054

    View details for PubMedID 6588871



    Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1-1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators. The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm. There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.

    View details for Web of Science ID A1984SN71300001

    View details for PubMedID 6200311



    Event-related potentials in two auditory target detection paradigms and two auditory paradigms without overt tasks were studied in 22 schizophrenic, 21 depressed, and 28 matched control subjects meeting Research Diagnostic Criteria. In the target detection paradigms, schizophrenics showed a pattern of reduced N120 amplitude and shorter P200 latency to frequently occurring tones, and reduced P300 and Slow Wave amplitude to infrequent target and nontarget tones. This pattern is consistent with impaired selective attention for stimuli. For depressed patients these variables were generally intermediate between those of schizophrenics and controls. In the other paradigms N120 latency was greater for schizophrenics, and P200 amplitude was less for depressed patients.

    View details for Web of Science ID A1981LM54300009

    View details for PubMedID 6939010

  • Acute and chronic effects of ethanol on event-related potentials. Advances in experimental medicine and biology Pfefferbaum, A., HORVATH, T. B., Roth, W. T., Clifford, S. T., KOPELL, B. S. 1980; 126: 625-639

    View details for PubMedID 7405699



    Auditory brain stem and cortical evoked potentials were recorded from 15 schizophrenics and 15 controls. There were significant cortical evoked potential differences between the two groups. However, brain stem evoked potentials were almost identical, suggesting that the cortical evoked potential differences are not due to peripheral factors such as inability to match sensory thresholds or defects in auditory acuity.

    View details for Web of Science ID A1980JK81900003

    View details for PubMedID 7417612

  • P300 and reaction time in schizophrenics and controls. Progress in brain research Roth, W. T., Pfefferbaum, A., HORVATH, T. B., KOPELL, B. S. 1980; 54: 522-525

    View details for PubMedID 7220962

  • Clinical application of sustained auditory evoked potentials. Progress in brain research Pfefferbaum, A., Roth, W. T., Ford, J. M., HORVATH, T. B., KOPELL, B. S. 1980; 54: 526-530

    View details for PubMedID 7220963

  • Effects of stimulus intensity on P300. Progress in brain research Roth, W. T., Doyle, C. M., Pfefferbaum, A., KOPELL, B. S. 1980; 54: 296-300

    View details for PubMedID 7220929



    Twelve elderly and 12 young women were subjects in a reaction-time task designed to elicit middle and late event-related potentials (ERP). The aged subjects differed from the young in respect to the later occurring ERP components: P2 was larger and later; P3 was later and had a different scalp distribution; the slow wave (SW) was smaller. In contrast, no age-related differences were found for N1 amplitude or latency. It is suggested that the diminution in SW amplitude contributes to the change in scalp distribution of P3 amplitude seen with age. The relationship of reaction time and P3 latency of single trials was examined by the adaptive filter technique. There was no difference between the old and young subjects as both groups revealed signficant, positive P3 latency-reaction time correlations.

    View details for Web of Science ID A1980KD59600006

    View details for PubMedID 6158403



    Eight healthy old and 12 healthy young women had event-related potentials (ERPs) recorded during the performance of a memory retrieval task. For each subject the single trial data recorded at Pz were analyzed using Woody's adaptive filter technique. The old subjects differed from the young in several respects: P3 amplitude at Pz was smaller, P3 latency and reaction time (RT) were greater, the relationship between P3 latency and RT was considerably altered. The adaptive filter increased the amplitude of P3 but the age-related amplitude difference persisted, suggesting that this difference is not due to increased latency variability with age. The old subjects had lower single trial P3-RT correlations and longer elapsed time from P3 peak to the response than did the young subjects. Both groups had greater RTs for outset items ('negative' responses) than for inset items ('positive' responses). For the young subjects P3 latency was also greater for the outset compared to the inset items but the difference was not found for the old subjects. Thus, the relationship between P3 latency and RT is altered in the aged--P3 and RT are less tightly coupled than in the young.

    View details for Web of Science ID A1980KD59600005

    View details for PubMedID 6158402



    Fifteen schizophrenics and 15 age-matched controls were compared on 3 auditory event-related potential (ERP) paradigms that elicited a variety of components. In one paradigm, tones were given at 0.75, 2.25 and 6.75 sec interstimulus intervals; in another, infrequently occurring targets in a reaction-time task were interspersed with frequent background stimuli; and, in a third, noise bursts or tones were delivered in a random sequence at either 70 or 100 dB SPL. The sensitivity of some of the ERP components in distinguishing schizophrenics from controls depended on the conditions under which the component was elicited. N1 amplitude was smaller in the schizophrenics than in the controls after longer interstimulus intervals. P2 amplitude was smaller in the schizophrenics than in the controls after longer interstimulus intervals. P2 amplitude was smaller in the schizophrenics only at higher stimulus intensities. P2 latency was shorter in schizophrenics except in the paradigm that varied interstimulus intervals. P3 amplitude, however, was much smaller in schizophrenics than controls ragardless of whether P3 was elicited by targets in a task or was elicited by 100 dB SPL stimuli. The loud stimuli also elicited blink reflexes that coincided with N1, but these reflexes did not vary by clinical group. Neither the amplitude of the slow wave following targets nor the sustained potential that accompanies prolonged auditory stimuli differed between schizophrenics and controls.

    View details for Web of Science ID A1980JE94500002

    View details for PubMedID 6153330



    Fifteen schizophrenics and 15 age-matched controls performed a reaction time (RT) task. A Bernoulli sequence of 85 dB SPL, 50 msec, 800 c/sec (P = 0.85) and 1200 c/sec (P = 0.15) tones was presented with an interstimulus interval of 1 sec. Subjects were instructed to press a button quickly upon hearing the 1200 c/sec tone. If a subject failed to respond within 650 msec, a 50 msec white noise burst occurred. In averages synchronized with target tones and computed without respect to RT, P3 was maximal at PZ with a mean latency of 330 msec for both schizophrenics and controls. P3 amplitude at PZ, however, averaged 6 muV in schizophrenics and 14 muV in controls (P < 0.001). Both mean RT and mean within-subject variance were greater in schizophrenices than controls. Other kinds of averages were computed to investigate the possibility that the amplitude differences were associated with different RTs or with differences in P3 latency variability in underlying trails. Averages of trials associated with short RTs (100--286 msec) had larger P3s than averages associated with long RTs (287--600 msec) (P < 0.01). Within each RT range, however, schizophrenic P3s were smaller than control P3s. Neither response-synchronized averaging nor adaptive filtering eliminated P3 amplitude differences between groups, indicating that P3 latency variability cannot account for these differences. We hypothesize that the smaller P3s in schizophrenics represent a deficit in reactivity to unexpected stimuli that is compatible with normal RT performance.

    View details for Web of Science ID A1980KH37100007

    View details for PubMedID 6158431

  • State-trait considerations of event-related potential markers of psychopathology. Psychopharmacology bulletin Pfefferbaum, A., Roth, W. T., KOPELL, B. S. 1979; 15 (1): 36-39

    View details for PubMedID 419247



    Neurophysiological changes in the central nervous system were demonstrated with EEG even-related potentials in healthy, aged women. Compared to young women, the aged women showed decreased amplitude of the late sustained potential (SP), increased P2 latency, disruption of the normal stimulus intensity-response amplitude function of P2 and increased amplitude of the P1 component. These age-related changes are interpreted as neurophysiological reflections of CNS deterioration found in non-senile elderly persons.

    View details for Web of Science ID A1979GD90100009

    View details for PubMedID 88334



    Ten chronic alcoholics (10+ year alcoholic drinking history) and ten age and sex matched controls were tested on an ERP paradigm which elicited a large P3 component. The N1 and P2 sensory evoked potential components did not differ in amplitude or latency between the two groups. The latency of the P3 was significantly longer for the alcoholics than the controls for both a response and non-response stimulus. This finding is consistent with the results seen in a variety of dementias and is offered as evidence of the dementing effects of prolonged alcoholism in this group of subjects. While the P3 latencies were prolonged for the alcoholics, their reaction times were not different from the controls. Single trial analysis using Woody's adaptive filter also demonstrated that the single trial estimates for the 3 latency were significantly prolonged for the alcoholics. The single trial correlation between the P3 latency and each trial's corresponding reaction time was significantly greater for the alcoholics than for the controls.

    View details for Web of Science ID A1979HY33700001

    View details for PubMedID 91494

  • EFFECTS OF ETHANOL AND MEPERIDINE ON AUDITORY EVOKED-POTENTIALS DRUG AND ALCOHOL DEPENDENCE Pfefferbaum, A., Roth, W. T., Tinklenberg, J. R., Rosenbloom, M. J., KOPELL, B. S. 1979; 4 (5): 371-380


    The effects of ethanol and meperidine on the auditory evoked potential (AEP) to stimuli of different intensities were investigated. Sixteen normal male volunteers received ethanol, 0.8 ml/kg, 100 mg meperidine, and a placebo on different days in a double-blind study. AEPs were recorded from Fz, Cz and Pz electrode placements. The stimuli were 500 msec 1000 Hz tones at 50, 60, 70 and 80 dB sound pressure level presented in a pseudo-random sequence. Meperidine had no significant effect on AEP variables. Ethanol reduced AEP activity between 24 and 250 msec but had no effect on the sustained potential measured between 300 and 450 msec.

    View details for Web of Science ID A1979GY68200001

    View details for PubMedID 510179



    We used an event-related brain potential (ERP) technique developed by Hillyard et al. (1973) to test abilities to attenuate irrelevant stimuli and to detect target stimuli. Subjects, 12 healthy old (80.3 years) and 12 healthy young adults (22.0 years), heard 1500 Hz tones in one ear and 800 Hz tones in the other ear. Infrequently, the pitch of either tone was raised. During one run, infrequent tones in the right ear were targets, and in the other run those in the left ear were targets. Subjects counted targets. For both groups, an early component of the ERP (N1) was larger to tones in the attended ear than in the unattended ear, and a later component (P3) was largest to the target. This suggests that both groups can attenuate irrelevant stimuli and can use stimulus probability information in this task. That P3 was later for old subjects suggests that they take longer to decide stimulus relevance.

    View details for Web of Science ID A1979GU67100010

    View details for PubMedID 429773



    Sixteen college-educated male subjects were given an object description task during placebo conditions and while intoxicated with marijuana extract cookies calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol, a dose within the range of usual social use. The task was scored for fluency, flexibility, elaboration, and uniqueness, all of which represent associational thinking and are considered to be components of creativity. Marijuana did not enhance any of these measures.

    View details for Web of Science ID A1978FA84600008

    View details for PubMedID 650201



    Twelve male college students received orally on different days NIMH marijuana extract calibrated to contain 0.7 mg/kg delta-9-tetrahydrocannabinol, 1.0 ml/kg 95% ethanol, and placebo in a double-blind balanced-order design. The contingent negative variation (CNV), auditory evoked potential (EP), heart rate (HR), and subjective measures of intoxication were recorded prior to drug ingestion and at regular intervals for 4.5 h postdrug. Both drugs produced significant subjective effects. Marijuana increased HR but did not have a significant effect on CNV amplitude or EP peak amplitudes and latencies. Ethanol increased HR, but not significantly, and reduced CNV amplitude and N1-P2 amplitude. Time-action curves for ethanol's effect on subjective high, HR, and N1-P2 amplitude were parallel, peaking between 0.5 and 1.5 h postdrug and returning to baseline by the end of testing. Time-action curve for ethanol's effect on the CNV showed continuing amplitude reduction throughout the test session.

    View details for Web of Science ID A1978EL13300003

    View details for PubMedID 415321

  • MARIHUANA AND MEMORY INTRUSIONS JOURNAL OF NERVOUS AND MENTAL DISEASE Pfefferbaum, A., DARLEY, C. F., Tinklenberg, J. R., Roth, W. T., KOPELL, B. S. 1977; 165 (6): 381-386


    Sixteen college-educated male subjects were tested on free-recall lists during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. On each testing day subjects studied six lists using a regular overt rehearsal procedure and six lists using an association-overt rehearsal procedure in which they were to rehearse alound both list items and associations to those items. Both marijuana and the association-rehearsal procedure reduced the number of correct recalls and increased the number of intrusions (nonlist items which were incorrectly recalled as having been on the list to be learned). The intrusions were divided into three categories: a) words found on prior lists; b) associates spoken during the rehearsal; or c) totally new works not previously mentioned. Marijuana significantly increased the number of new intrusions; the association-rehearsal procedure did not. This result suggests that one of the effects of marijuana on cognitive functions in humans is to increase the number of intrusive thoughts and this may be the mechanism involved in some of the thought disorder observed with marijuana intoxication.

    View details for Web of Science ID A1977EF05800003

    View details for PubMedID 591936



    Twelve men performed the Sternberg memory retrieval task under three experimental conditions: after oral doses of marihuana extract calibrated to contain 0.7 mg/kg delta9-tetrahydrocannabinol (THC), 1.0 ml/kg 95% ethanol, or placebo. Simultaneously, the EEG was recorded from Ca to linked ears and the EOG from leads above and below the right eye. In this task, subjects saw a set of 1 to 4 digits follwed by a warning tone that was followed 1.5 sec later by a test digit. Subjects indicated by pressing one of two buttons whether the test digit was in-set or out-of-the-set. There were no drug effects on N1 in the evoked potential to the warning tone, but P3 amplitude was smaller under THC and ethanol than under placebo. CNV amplitude in the interval between the warning tone and the test digit showed no drug effects, indicating that the subject was equally prepared for the test digit regardless of drug received. However, the latency of 50% resolution of the CNV was longer under THC than under placebo. THC also increased the reaction time for each set size by about 75 msec above the values for ethanol and placebo, the latter two not differing significantly. Set size affected N1 and P3 amplitudes and latencies and CNV amplitude, as well as 50% CNV resolution latency and reaction time, but there were no drug chi set size interactions.

    View details for Web of Science ID A1977CY78100008

    View details for PubMedID 65273



    Performance on a time production task, heart rate, and subjective responses were studied in twelve male sujects given oral doses of marijuana (0.7 mg of delta-9-tetrahydrocannabinol/kg), ethanol (1.0 ml/kg), and placebo, on three testing days which were each separated by 1 week. Orders were balanced across subjects and testing conditions were double-blind. Compared to ethanol and placebo, marijuana induced a significant under-production of time intervals, suggesting an acceleration of the internal rate of time perception. The onset of this acceleration of time sense in which geophysical time seemed to pass slowly corresponded with the characteristic increase in heart rate and the onset of the subjective feelings of drug effects. Initial phases of alcohol intoxication were associated with the opposite effects on the time production task. These findings replicate previous work and indicate that an easily administered time production task provides a consistent, non-motor measure of acute marijuana intoxication and also reflects ethanol intoxication.

    View details for Web of Science ID A1976CH51700010

    View details for PubMedID 826945

  • MARIHUANA EFFECTS ON TAT FORM AND CONTENT PSYCHOPHARMACOLOGIA Roth, W. T., Rosenbloom, M. J., DARLEY, C. F., Tinklenberg, J. R., KOPELL, B. S. 1975; 43 (3): 261-266


    In a double-blind study, 72 normal male subjects were given either placebo or marihuana containing 20 mg. Delta-9-tetrahydrocannabinol. Stories written to cards selected from the Thematic Apperception Test did not differ on hostile or sexual content scales between drug and placebo conditions, but 6 out of 10 scales specifically constructed to detect marihuana effects were successful at differentiating the two conditions. Under marihuana the stories had a timeless, non-narrative quality, with greater discontinuity in thought sequence and more frequent inclusion of contradictory ideas. Novelty of content was somewhat increased by marihuana, while relation to the picture, imagery, repetition, and closure were not significantly affected.

    View details for Web of Science ID A1975AR45700011

    View details for PubMedID 1103209

  • Proceedings: Drugs, delinquency, and aggression. Psychopharmacology bulletin Tinklenberg, J. R., KOPELL, B. S., Roth, W. T., Darley, C. 1974; 10 (4): 62-63

    View details for PubMedID 4431879

Conference Proceedings

  • Cardio-respiratory instabilities precede the onset of naturally occurring panic attacks Meuret, A. E., Rosenfield, D., Zhou, E., Conrad, A., Wilhelm, F. H., Roth, W. T. ELSEVIER SCIENCE BV. 2011: 173-174
  • A discrete or dimensional affective landscape? Evidence for emotion discreteness from a multiple-response-levels analysis of film-induced fear and sadness Kreibig, S. D., Wilhelm, F. H., Roth, W. T., Gross, J. J. PSYCHOLOGY PRESS. 2008: 203-203
  • Psychophysiological responses to breathing instructions Mueller, A., Roth, W. T., Conrad, A., Doberenz, S., Kim, S., Meuret, A. E. ELSEVIER SCIENCE BV. 2007: 209-209
  • Clinical anxiety and respiration: Palo Alto studies in progress Roth, W. T., Kim, S., Wollburg, E., Conrad, A., Doberenz, S., Mueller, A., Meuret, A. E. ELSEVIER SCIENCE BV. 2007: 212-212
  • Are the psychophysiological responses to voluntary hyperventilation diagnostically specific to panic disorder? Wollburg, E., Roth, W. T., Conrad, A., Mueller, A., Doberenz, S., Meuret, A. E., Kim, S. WILEY-LISS. 2007: 371-373
  • The psychophysiology of fear and sadness: Cardiovascular, electrodermal, and respiratory responses during film viewing Kreibig, S. D., Wilheim, F. H., Gross, J. J., Roth, W. T. WILEY-BLACKWELL. 2007: S20-S20
  • Affective computing: uSing computational intelligence techniques to classify the psychophysiological signatures of fearful, sad, and calm affective states Wilhelm, F. H., Kolodyazhniy, V., Kreibig, S. D., Roth, W. T., Gross, J. J. WILEY-BLACKWELL. 2007: S110-S111
  • Differential effects of film-induced fear and sadness on acoustic startle Kreibig, S. D., Wilhelm, F. H., Roth, W. T., Gross, J. J. WILEY-BLACKWELL PUBLISHING, INC. 2006: S54-S54
  • Standardized assessment of diurnal vagal activity in depressed patients with risk for coronary artery disease: accounting for physical activity, respiration, and mood variability Wilhelm, F. H., Conrad, A., Luce, K. H., Celio, C. L., DeLorenzo, A., Roth, W. T., Grossman, P., Taylor, C. B. ELSEVIER SCIENCE BV. 2004: 410-410
  • Circadian positive and negative affect and heart rate variability in depressed and nondepressed individuals at risk for cardiovascular disease Wilhelm, F. H., Grossman, P., Conrad, A., Luce, K. H., Roth, W. T., Taylor, C. B. HOGREFE & HUBER PUBLISHERS. 2004: 227-227
  • Situational and individual response specificity to emotion films: Effects on experiential, cardiovascular, electrodermal, respiratory and somatic responses Kreibig, S. D., Wilhelm, F. H., Gross, J. J., Ferst, R., Roth, W. T. WILEY-BLACKWELL. 2004: S75-S75
  • A new technology for 24-h assessment of RSA with control for respiratory and physical activity variation Wilhelm, F. H., Grossman, P., Meuret, A. E., Taylor, C. B., Roth, W. T. ELSEVIER SCIENCE BV. 2003: 241-242
  • Social anxiety and response to touch: incongruence between self-evaluative and physiological reactions Wilhelm, F. H., Kochar, A. S., Roth, W. T., Gross, J. J. ELSEVIER SCIENCE BV. 2001: 181-202


    Touch is an important form of social interaction, and one that can have powerful emotional consequences. Appropriate touch can be calming, while inappropriate touch can be anxiety provoking. To examine the impact of social touching, this study compared socially high-anxious (N=48) and low-anxious (N=47) women's attitudes concerning social touch, as well as their affective and physiological responses to a wrist touch by a male experimenter. Compared to low-anxious participants, high-anxious participants reported greater anxiety to a variety of social situations involving touch. Consistent with these reports, socially anxious participants reacted to the experimenter's touch with markedly greater increases in self-reported anxiety, self-consciousness, and embarrassment. Physiologically, low-anxious and high-anxious participants showed a distinct pattern of sympathetic-parasympathetic coactivation, as reflected by decreased heart rate and tidal volume, and increased respiratory sinus arrhythmia, skin conductance, systolic/diastolic blood pressure, stroke volume, and respiratory rate. Interestingly, physiological responses were comparable in low and high-anxious groups. These findings indicate that social anxiety is accompanied by heightened aversion towards social situations that involve touch, but this enhanced aversion and negative-emotion report is not reflected in differential physiological responding.

    View details for Web of Science ID 000172496600001

    View details for PubMedID 11698114

  • ELDERLY MEN AND WOMEN ARE LESS RESPONSIVE TO STARTLING NOISES - N1, P3 AND BLINK EVIDENCE Ford, J. M., Roth, W. T., Isaacks, B. G., White, P. M., Hood, S. H., Pfefferbaum, A. ELSEVIER SCIENCE BV. 1995: 57-80


    Previously we observed that the P3 component of the event-related brain potential (ERP) elicited by startling noises, and to a lesser extent P3 to target tones, is reduced in the elderly (Ford & Pfefferbaum, 1991). In the current experiment, we tried to eliminate possible effects of age-related hearing deficits on the responses to noises by filtering them to include only frequencies heard best by the elderly (0-1000 Hz) and by setting noise intensity relative to each subject's threshold (sensation level, SL). Twelve younger (mean 22 years) and 12 older (mean 69 years) men and women listened to three sequences of tones (80%, 500 Hz, 70 dB SPL) and noises (20%). One type of noise occurred in each sequence (wide band noise set to 107 dB SPL, narrow band noise set to 107 dB SPL, or narrow band noise set to approximately 65 dB SL). The order of the three sequences was counterbalanced across age and sex. Younger subjects blinked to the noise 4-5 times more often than older subjects and had N1 and P3 amplitudes that were 2-3 times larger, regardless of the noise type. N1 amplitude to the background frequent tones and non-startle blinks did not differ between groups. Thus, even when noises were narrow band and set relative to each subject's threshold, older subjects were less responsive to startling auditory stimuli than were younger.

    View details for Web of Science ID A1995QE66900001

    View details for PubMedID 7734630

Stanford Medicine Resources: