Plasma oxytocin concentrations are lower in depressed vs. healthy control women and are independent of cortisol
JOURNAL OF PSYCHIATRIC RESEARCH
2014; 51: 30-36
HPA axis genetic variation, cortisol and psychosis in major depression
2014; 19 (2): 220-227
The neuropeptide oxytocin (OT) promotes social behavior and attenuates stress responsivity in mammals. Recent clinical evidence suggests OT concentrations may be dysregulated in major depression. This study extends previous research by testing whether: 1) OT concentrations vary systematically in depressive disorders with and without hypercortisolemia, 2) gender differences in OT concentrations are observed in depressed vs. healthy control participants, and 3) OT concentrations are predictive of clinical phenotypes. Plasma OT concentrations of psychotic major depressive (PMD; n = 14: 10 female, 4 male), non-psychotic major depressive (NPMD; n = 17: 12 female, 5 male), and non-depressed, healthy control (n = 19: 11 female, 8 male) participants were assayed at 2000, 2400, 0400, and 0800 h. Plasma cortisol concentrations were quantified at 2300 h, and clinical phenotypes were determined. As expected, PMD participants, compared to NPMD and healthy control participants, showed higher plasma cortisol concentrations. Although both depressed groups showed similar OT concentrations, a significant interaction effect between group and gender was observed. Specifically, depressed females exhibited lower mean OT concentrations than depressed males. Further, depressed vs. healthy control female participants exhibited lower mean OT concentrations, whereas depressed vs. healthy control male participants showed a trend in the opposite direction. OT concentrations were also predictive of desirability, drug dependence, and compulsivity scores as measured by the Million Clinical Multiaxial Inventory-III. All findings were independent of cortisol. These data suggest that OT signaling may provide a mechanism by which to better understand female-biased risk to develop depressive disorders and that plasma OT concentrations may be a useful biomarker of certain clinical phenotypes.
View details for DOI 10.1016/j.jpsychires.2013.12.012
View details for Web of Science ID 000332909500004
Clinical management of alcohol use disorders in the neurology clinic.
Handbook of clinical neurology
2014; 125: 659-670
Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with non-psychotic major depression (NPMD); and 29 HCs. Collection of genetic material was added one third of the way into a larger study on cortisol, cognition and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 1800 to 0900 h and for the assessment of alleles for six genes involved in HPA axis regulation. Two of the six genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression and psychosis, and medication status, only allelic variation for the glucocorticoid receptor (GR) gene accounted for a significant variance for mean cortisol levels from 1800 to 0100 h (r(2)=0.288) and from 0100 to 0900 h (r(2)=0.171). In addition, GR and corticotropin-releasing hormone receptor 1 (CRHR1) genotypes contributed significantly to psychosis measures and CRHR1 contributed significantly to depression severity rating.Molecular Psychiatry advance online publication, 29 October 2013; doi:10.1038/mp.2013.129.
View details for DOI 10.1038/mp.2013.129
View details for Web of Science ID 000330706800019
View details for PubMedID 24166410
Recovery-oriented policy and care systems in the UK and USA.
Drug and alcohol review
2014; 33 (1): 13-18
Alcohol misuse adversely affects health outcomes, but alcohol misuse and alcohol use disorders (AUDs) are often ignored by healthcare providers in primary and specialty ambulatory care clinics. Data show that early identification and brief intervention for alcohol misuse in these settings can effectively reduce alcohol consumption and its medical sequelae. The aim of this chapter is to review the epidemiology of problematic alcohol use in ambulatory care settings, the diagnostic criteria for AUDs, the approach called SBIRT (screening, brief intervention and referral to treatment) as a model program to target alcohol misuse in everyday clinical practice, when and how to refer patients to resources beyond the clinic for their alcohol use problems, and the medical illnesses associated with AUDs.
View details for DOI 10.1016/B978-0-444-62619-6.00039-2
View details for PubMedID 25307603
Pharmacotherapy for Alcohol Dependence: Perceived Treatment Barriers and Action Strategies Among Veterans Health Administration Service Providers
2013; 10 (4): 410-419
The concept of recovery has been an influence on addicted individuals for many decades. But only in the past 15 years has the concept had a purchase in the world of public policy. In the USA, federal and state officials have promulgated policies intended to foster 'recovery-oriented systems of care' and have ratified recovery-supportive laws and regulations. Though of more recent vintage and therefore less developed, recovery policy initiatives are also being implemented in the UK. The present paper describes recovery-oriented policy in both countries and highlights key evaluations of the recovery-oriented interventions.
View details for DOI 10.1111/dar.12092
View details for PubMedID 24267515
From self-medication to intoxication: time for a paradigm shift.
2013; 108 (4): 670-671
Why doctors prescribe opioids to known opioid abusers. How cultural attitudes and financial disincentives affect the prescribing habits of physicians.
2013; 96 (3): 36-37
Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression.
2013; 211 (2): 119-126
Although access to and consideration of pharmacological treatments for alcohol dependence are consensus standards of care, receipt of these medications by patients is generally rare and highly variable across treatment settings. The goal of the present project was to survey and interview the clinicians, managers, and pharmacists affiliated with addiction treatment programs within Veterans Health Administration (VHA) facilities to learn about their perceptions of barriers and facilitators regarding greater and more reliable consideration of pharmacological treatments for alcohol dependence. Fifty-nine participants from 19 high-adopting and 11 low-adopting facilities completed the survey (facility-level response rate = 50%) and 23 participated in a structured interview. The top 4 barriers to increased consideration and use of pharmacotherapy for alcohol dependence were consistent across high- and low-adopting facilities and included perceived low patient demand, pharmacy procedures or formulary restrictions, lack of provider skills or knowledge regarding pharmacotherapy for alcohol dependence, and lack of confidence in treatment effectiveness. Low patient demand was rated as the most important barrier for oral naltrexone and disulfiram, whereas pharmacy or formulary restrictions were rated as the most important barrier for acamprosate and extended-release naltrexone. The 4 strategies rated across low- and high-adopting facilities as most likely to facilitate consideration and use of pharmacotherapy for alcohol dependence were more education to patients about existing medications, more education to health care providers about medications, increased involvement of physicians in treatment for alcohol dependence, and more compelling research on existing medications. This knowledge provides a foundation for designing, deploying, and evaluating targeted implementation efforts.
View details for DOI 10.1037/a0030949
View details for Web of Science ID 000327182400007
View details for PubMedID 23356858
Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression
2013; 211 (2): 119-126
The mineralocorticoid receptor agonist, fludrocortisone, differentially inhibits pituitary-adrenal activity in humans with psychotic major depression
2013; 38 (1): 115-121
Psychotic major depression (PMD) is associated with deficits in verbal memory as well as other cognitive impairments. This study investigated brain function in individuals with PMD during a verbal declarative memory task. Participants included 16 subjects with PMD, 15 subjects with non-psychotic major depression (NPMD) and 16 healthy controls (HC). Functional magnetic resonance imaging (fMRI) data were acquired while subjects performed verbal memory encoding and retrieval tasks. During the explicit encoding task, subjects semantically categorized words as either "man-made" or "not man-made." For the retrieval task, subjects identified whether words had been presented during the encoding task. Functional MRI data were processed using SPM5 and a group by condition ANOVA. Clusters of activation showing either a significant main effect of group or an interaction of group by condition were further examined using t-tests to identify group differences. During the encoding task, the PMD group showed lower hippocampus, insula, and prefrontal activation compared to HC. During the retrieval task, the PMD group showed lower recognition accuracy and higher prefrontal and parietal cortex activation compared to both HC and NPMD groups. Verbal retrieval deficits in PMD may be associated with deficient hippocampus function during encoding. Increased brain activation during retrieval may reflect an attempt to compensate for encoding deficits.
View details for DOI 10.1016/j.pscychresns.2012.06.008
View details for PubMedID 23149036
Time to Abandon the Self-Medication Hypothesis in Patients with Psychiatric Disorders
AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE
2012; 38 (6): 524-529
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been linked with major depression, particularly psychotic major depression (PMD), with mineralocorticoid receptors (MRs) playing a role in HPA-axis regulation and the pathophysiology of depression. Herein we hypothesize that the MR agonist fludrocortisone differentially inhibits the HPA axis of psychotic major depression subjects (PMDs), non-psychotic major depression subjects (NPMDs), and healthy control subjects (HCs).Fourteen PMDs, 16 NPMDs, and 19 HCs were admitted to the Stanford University Hospital General Clinical Research Center. Serum cortisol levels were sampled at baseline and every hour from 18:00 to 23:00h, when greatest MR activity is expected, on two consecutive nights. On the second afternoon at 16:00h all subjects were given 0.5mg fludrocortisone. Mean cortisol levels pre- and post-fludrocortisone and percent change in cortisol levels were computed.There were no significant group differences for cortisol at baseline: F(2,47)=.19, p=.83. There were significant group differences for post-fludrocortisone cortisol: F(2,47)=5.13, p=.01, which were significantly higher in PMDs compared to HCs (p=.007), but not compared to NPMDs (p=.18). There were no differences between NPMD's and HC's (p=.61). Also, PMDs had a lower percent change from baseline in cortisol levels at 2200h than NPMDs (p=.01) or HCs (p=.009).Individuals with psychotic major depression compared to healthy control subjects have diminished feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in response to the mineralocorticoid receptor agonist fludrocortisone. To our knowledge, this is the first study to examine HPA axis response to MR stimulation in major depression (with and without psychosis), and only the third study to demonstrate that exogenously administered fludrocortisone can down-regulate the HPA axis in humans.
View details for DOI 10.1016/j.psyneuen.2012.05.006
View details for Web of Science ID 000313761000011
View details for PubMedID 22727477
Why Doctors Prescribe Opioids to Known Opioid Abusers
NEW ENGLAND JOURNAL OF MEDICINE
2012; 367 (17): 1580-1581
The relationships of positive and negative symptoms with neuropsychological functioning and their ability to predict verbal memory in psychotic major depression
2012; 198 (1): 34-38
The Self-Medication Hypothesis (SMH) of addictive disorders as articulated by Edward Khantzian in his seminal 1985 paper postulates that individuals with psychiatric disorders use substances to relieve psychiatric symptoms and that this pattern of usage predisposes them to addiction. Khantzian's SMH also postulates that the preferred substance is not random, but is based on the unique pharmacological properties of the substance. For example, an individual with attention deficit disorder would prefer amphetamines to alcohol, due to its stimulating properties, whereas an individual with anxiety would prefer alcohol to amphetamines, due to its anxiolytic properties. Finally, Khantzian's SMH implies that treating the underlying psychiatric disorder will improve or resolve the problems of addiction. AIMS AND RESULTS: A review of the scientific literature demonstrates a striking lack of robust evidence in support of the SMH as put forth by Khantzian.Nonetheless, the SMH has had a profound influence on medical and lay culture, as well as clinical care. Although originally formulated as a compassionate explanation for addiction in those with psychiatric disorders, the SMH does not provide, as originally intended, a "useful rationale" for guiding treatment and instead has led to under-recognition and under-treatment of substance use disorders.
View details for DOI 10.3109/00952990.2012.694532
View details for Web of Science ID 000309667200002
View details for PubMedID 22924576
Alcohol Screening Scores and the Risk of New-Onset Gastrointestinal Illness or Related Hospitalization
JOURNAL OF GENERAL INTERNAL MEDICINE
2011; 26 (7): 777-782
Neuropsychological functioning, in relation to positive and negative symptoms in psychotic major depression (PMD), has not been as thoroughly studied as it has been in schizophrenia. Thus, the current study investigated the associations between positive and negative symptoms with cognitive functioning, with an emphasis on verbal memory in PMD. Attention, working memory, and the executive functioning domains were analyzed among 49 PMD participants. Positive symptoms did not correlate significantly with any measures of verbal memory but did correlate with one measure of attention, working memory, and executive functioning. Negative symptoms correlated significantly with two California Verbal Learning Test-II (CVLT-II) measures of verbal memory and three measures of executive function. Hierarchical regressions were conducted to determine if negative symptoms could predict verbal memory performance after controlling for depression. Of the two verbal memory measures, negative symptoms significantly explained additional variance for CVLT Recognition, but not for CVLT Trials 1-5 total score. Our results provide some evidence that, consistent with the schizophrenia literature, negative symptoms contributed more to verbal memory deficits in PMD than positive symptoms, regardless of depression severity.
View details for DOI 10.1016/j.psychres.2011.12.001
View details for Web of Science ID 000313848200007
View details for PubMedID 22410589
Depression and smoking cessation: does the evidence support psychiatric practice?
Neuropsychiatric disease and treatment
2007; 3 (4): 487-493
Excessive alcohol use is associated with a variety of negative health outcomes, including liver disease, upper gastrointestinal bleeding, and pancreatitis.To determine the 2-year risk of gastrointestinal-related hospitalization and new-onset gastrointestinal illness based on alcohol screening scores.Retrospective cohort study.Male (N = 215, 924) and female (N = 9,168) outpatients who returned mailed questionnaires and were followed for 24 months.Alcohol Use Disorder Identification Test-Consumption Questionnaire (AUDIT-C), a validated three-item alcohol screening questionnaire (0-12 points).Two-year risk of hospitalization with a gastrointestinal disorder was increased in men with AUDIT-C scores of 5-8 and 9-12 (OR 1.54, 95% CI = 1.27-1.86; and OR 3.27; 95% CI = 2.62-4.09 respectively), and women with AUDIT-C scores of 9-12 (OR 6.84, 95% CI = 1.85 - 25.37). Men with AUDIT-C scores of 5-8 and 9-12 had increased risk of new-onset liver disease (OR 1.49, 95% CI = 1.30-1.71; and OR 2.82, 95% CI = 2.38-3.34 respectively), and new-onset of upper gastrointestinal bleeding (OR 1.28, 95% CI = 1.05-1.57; and OR 2.14, 95% CI = 1.54-2.97 respectively). Two-year risk of new-onset pancreatitis in men with AUDIT -C scores 9-12 was also increased (OR 2.14; 95% CI = 1.54-2.97).Excessive alcohol use as determined by AUDIT-C is associated with 2-year increased risk of gastrointestinal-related hospitalization in men and women and new-onset liver disease, upper gastrointestinal bleeding, and pancreatitis in men. These results provide risk information that clinicians can use in evidence-based conversations with patients about their alcohol consumption.
View details for DOI 10.1007/s11606-011-1688-7
View details for Web of Science ID 000291701200019
View details for PubMedID 21455813
Psychotherapy, symptom outcomes, and role functioning over one year among patients with bipolar disorder
2006; 57 (7): 959-965
Depression and smoking are highly comorbid. The vast majority of psychiatrists treating depressed patients do not target or treat nicotine dependence, and many inpatient psychiatric facilities implicitly condone smoking by providing 'smoke breaks'. The reasons for failure to treat are unclear, but are probably linked to the notion that depressed smokers are neither willing nor able to quit, and will become more depressed if they try. We review the clinical evidence on depression and smoking cessation, and find little support for current psychiatric practice. Although quitting smoking does appear to pose a risk for the development of depression, this risk is not clearly higher in those with a past history of depression than those without. Depressed smokers are as capable as nondepressed smokers of quitting smoking, and at least one-quarter of depressed smokers is willing to try. Sustained abstinence may even lead to improvement in depressive disorders. More research is needed to understand the relationship between depression and quitting smoking, but current clinical evidence suggests more resiliency among depressed smokers than common clinical wisdom would dictate.
View details for PubMedID 19300577
Update on augmentation of antidepressant response in resistant depression.
Current psychiatry reports
2005; 7 (6): 435-440
Randomized trials indicate that psychosocial interventions effective adjuncts to pharmacotherapy in bipolar disorder (1,2). A one-year naturalistic-prospective design was used to examine the association between psychotherapy use and the symptomatic and functional outcomes of patients with bipolar disorder.Patients with bipolar disorder in a depressed phase (N=248) were drawn from the first 1,000 enrollees (November 1999 to April 2002) in the Systematic Treatment Enhancement Program (STEP-BD), a study of patients with bipolar disorder receiving best-practice pharmacotherapy. Patients were seen clinics and interviewed every three months over one year regarding of psychotherapy services, symptoms, and role functioning. Mixed-effects regression models were used to examine whether the amount of psychotherapy the patients received during each three-month interval was associated with symptomatic or psychosocial functioning during the same or a subsequent three-month interval.During the study year, percent of the patients had at least one psychotherapy session. Among patients who began an interval with severe depressive symptoms or low functioning, having more frequent sessions of psychotherapy was associated with less severe mood symptoms and better functioning in the same or a subsequent study interval. In contrast, among patients who began interval with less severe depressive symptoms or higher functioning, fewer psychotherapy sessions were associated with less severe depressive symptoms and greater functioning in the same or a subsequent interval.Intensive psychotherapy may be most applicable to severely ill patients with bipolar disorder, whereas briefer treatments may be adequate for less severely ill patients.
View details for Web of Science ID 000238706800007
View details for PubMedID 16816280
Psychosocial service utilization by patients with bipolar disorders: data from the first 500 participants in the Systematic Treatment Enhancement Program.
Journal of psychiatric practice
2004; 10 (2): 81-87
Most patients in acute depression trials fail to achieve remission with antidepressant monotherapy. Many patients seem to require more than one medication to achieve remission or adequate response. Augmentation strategies are commonly used in clinical practice, but most have been poorly studied. In addition, better-studied strategies, such as the use of lithium and thyroid augmentation, have not been well investigated in combination with newer antidepressants. Various novel strategies are being investigated as augmenting agents, including selective dopamine agonists, sex steroids, norepinephrine reuptake inhibitors, glucocorticoid-specific agents, and newer anticonvulsants. We review the status of augmentation strategies in the treatment of depression.
View details for PubMedID 16318821
A prospective trial of modafinil as an adjunctive treatment of major depression
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2004; 24 (1): 87-90
Although patients with bipolar disorder have been shown to benefit from psychosocial interventions, the proportion that utilizes these interventions is unknown. We set out to clarify the determinants of psychosocial service utilization in adults with bipolar disorder.We investigated psychosocial service utilization among the first 500 patients admitted to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).In the 3 months prior to enrollment in STEP-BD, a majority of the patients (54%) were engaged in at least one psychosocial service modality in addition to pharmacotherapy. In order of decreasing frequency, these were therapy with a psychologist, self-help group, therapy with a social worker, and therapy with another type of provider. Bipolar patients with personality disorders (80% vs 20%, p = 0.0002), alcohol/drug abuse disorders (76% vs 24%, p = 0.0022), and anxiety disorders (60% vs 40%, p = 0.0043) received more psychosocial services than those without. Poorer global functioning also increased the likelihood of receiving services, whereas being married decreased service utilization.Psychosocial service utilization by outpatients with bipolar disorder is strongly linked to greater severity/complexity of illness. Potential moderators, such as insurance status and availability of care, should be examined in future studies.
View details for PubMedID 15330403
Why is this special issue on women's professional development in psychiatry necessary?
2004; 28 (4): 275-277
Current status of the utilization of antiepileptic treatments in mood, anxiety and aggression: Drugs and devices
CLINICAL EEG AND NEUROSCIENCE
2004; 35 (1): 4-13
Modafinil is a wake-promoting agent approved by the Federal Drug Administration for the treatment of narcolepsy. Preliminary evidence indicates that modafinil may improve fatigue and excessive sleepiness associated with a variety of conditions. The purpose of this study was to investigate the utility of modafinil as an adjunctive treatment of depressed patients. Subjects with a history of major depression with partial response on a stable therapeutic dose of an antidepressant were eligible to participate. All subjects endorsed complaints of significant fatigue and/or excessive sleepiness on clinical assessment. Modafinil was added to their existing regimen at a dose of 100 to 400 mg/d for 4 weeks. Subjects were assessed at 2-week intervals for improvement using the standard depression scales (HDRS, BDI, CGI), fatigue scales (VASF, FSI), and a neuropsychologic battery. Thirty-five subjects were entered and 31 subjects completed the 4-week trial. Significant improvements were seen across all 3 measures of depression (HDRS, BDI, CGIS) and both measures of fatigue (VASF, FSI). On the neurocognitive battery, significant gains in the Stroop Interference Test were seen at 4 weeks, whereas the other cognitive tests showed no change. Modafinil may be a useful and a well-tolerated adjunctive agent to standard antidepressants in the treatment of major depression.
View details for DOI 10.1097/01.jcp.0000104910.75206.b9
View details for Web of Science ID 000188093400015
View details for PubMedID 14709953
A Friday in the life of an academic psychiatrist
2003; 27 (3): 214-215
Safety of antidepressants in the elderly.
Expert opinion on drug safety
2003; 2 (4): 367-383
Interventions that have been utilized to control seizures in people with epilepsy have been employed by the psychiatric community to treat a variety of disorders. The purpose of this review will be to give an overview of the most prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of psychiatric disease states. By far, the most prevalent use of these interventions is in the treatment of mood disorders. AEDs have become a mainstay in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food and Drug Administration has approved the use of valproic acid for acute mania, and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are emerging as possibly useful tools in the treatment of more refractory depressive illness.
View details for Web of Science ID 000223764000002
View details for PubMedID 15112459
Neural correlates of timbre change in harmonic sounds
2002; 17 (4): 1742-1754
Until the 1980s, the two major classes of antidepressants, the tricyclics and the monoamine oxidase inhibitors (MAOIs), were effective but had severe side effects, requiring monitoring by psychiatrists. The past several years have brought new classes of antidepressants that are safer for the patient to take and far easier for the non-psychiatrist to prescribe. Whilst this is of enormous value, it leaves the physician with the dilemma of which one to prescribe. These new antidepressants cannot safely be used interchangeably. This paper will discuss each of the antidepressants presently available, with particular emphasis on safety in the elderly. Drug interactions, side effects and particular challenges to the older patient will be described. The authors will then advise a general strategy for prescribing antidepressants.
View details for PubMedID 12904093
The status of evidence-based guidelines and algorithms in the treatment of depression
2002; 32 (11): 658-663
Olanzapine in diverse syndromal and subsyndromal exacerbations of bipolar disorders
2002; 4 (5): 328-334
Timbre is a major structuring force in music and one of the most important and ecologically relevant features of auditory events. We used sound stimuli selected on the basis of previous psychophysiological studies to investigate the neural correlates of timbre perception. Our results indicate that both the left and right hemispheres are involved in timbre processing, challenging the conventional notion that the elementary attributes of musical perception are predominantly lateralized to the right hemisphere. Significant timbre-related brain activation was found in well-defined regions of posterior Heschl's gyrus and superior temporal sulcus, extending into the circular insular sulcus. Although the extent of activation was not significantly different between left and right hemispheres, temporal lobe activations were significantly posterior in the left, compared to the right, hemisphere, suggesting a functional asymmetry in their respective contributions to timbre processing. The implications of our findings for music processing in particular and auditory processing in general are discussed.
View details for DOI 10.1006/nimg.2002.1295
View details for Web of Science ID 000179969800008
View details for PubMedID 12498748
Impaired recognition of facial emotion in mania
AMERICAN JOURNAL OF PSYCHIATRY
2002; 159 (2): 302-304
To evaluate effects of olanzapine in diverse exacerbations of bipolar disorders.Twenty-five evaluable bipolar disorder [14 bipolar I (BPI), 10 bipolar II (BPII) and one bipolar disorder not otherwise specified (BP NOS)] outpatients received open olanzapine (15 adjunctive, 10 monotherapy). Thirteen had elevated (11 syndromal, two subsyndromal) and 12 depressed (four syndromal, eight subsyndromal) mood symptoms of at least mild severity, with Clinical Global Impression-Severity (CGI-S) scores of at least 3. Only one had psychotic symptoms.With open olanzapine (15 adjunctive, 10 monotherapy), overall symptom severity (CGI-S) as well as mood elevation (Young Mania Rating Scale), depression (Hamilton and Montgomery-Asberg Depression Rating Scales), and anxiety (Hamilton Anxiety Rating Scale), rapidly decreased (significantly by days 2-3). Patients with the greatest baseline severity (CGI-S) had the greatest improvement. Fifteen of 25 (60%) patients responded. Time to consistent response was bimodal, with five early (by 0.5 +/- 0.3 weeks) and 10 late (by 7.0 +/- 1.9 weeks) responders. Early compared with late responders had 51% lower final olanzapine doses. Olanzapine was generally well tolerated, with sedation and weight gain the most common adverse effects.Olanzapine was effective in diverse exacerbations of bipolar disorders. The bimodal distribution of time to response and different final doses are consistent with differential mechanisms mediating early compared with late responses. Controlled studies are warranted to further explore these preliminary observations.
View details for Web of Science ID 000178520500009
View details for PubMedID 12479666
Depression in Individuals with Epilepsy.
Current treatment options in neurology
2000; 2 (6): 571-585
Recognition of facial emotion was examined in manic subjects to explore whether aberrant interpersonal interactions are related to impaired perception of social cues.Manic subjects with bipolar I disorder (N=8), euthymic subjects with bipolar I (N=8) or bipolar II (N=8) disorder, and healthy comparison subjects (N=10) matched pictures of faces to the words "fear," "disgust," "anger," "sadness," "surprise," and "happiness."The manic subjects showed worse overall recognition of facial emotion than all other groups. They showed worse recognition of fear and disgust than the healthy subjects. The euthymic bipolar II disorder subjects showed greater fear recognition than the manic and euthymic bipolar I disorder subjects.Impaired perception of facial emotion may contribute to behaviors in mania. Impaired recognition of fear and disgust, with relatively preserved recognition of other basic emotions, contrasts with findings for depression and is consistent with a mood-congruent positive bias.
View details for Web of Science ID 000173727500020
View details for PubMedID 11823275
Isolated meningeal vasculopathy associated with Clostridium septicum infection
1997; 48 (1): 265-267
Depression in epilepsy patients is not only extremely common, but is often poorly recognized and inadequately treated. Depression can have significant consequences including increased medical utilization, poor quality of life, social disability, and mortality. Etiology of depression is multifaceted with prominent psychosocial determinants. Salient medical issues include iatrogenic causes, especially side effects of antiepileptic drugs (AEDs). In addition, seizures with increased frequency and with "forced normalization" can be associated with mood disturbance. After a thorough search for correctable causes, treatment should not be delayed, and should include both psychotherapy and pharmacologic therapies. Antidepressants remain the mainstay of pharmacologic intervention with the selective serotonin reuptake inhibitors (SSRIs) considered first-line treatment. Venlafaxine, nefazadone, and tricyclic antidepressants (TCAs) can also be used, but with some important caveats. Decreasing the seizure threshold is a common side effect of all antidepressants, but the risk can be minimized and should not prevent vigorous treatment of the depressive state. Other side effects present with varying frequency from the common (eg, sexual dysfunction as seen with SSRIs) to uncommon withdrawal reactions and rare complications of serotonin syndrome. Depression must also be considered a recurring disease, and when a successful regimen is ascertained, adequate continuation of treatment is a necessity. Care must be taken to treat the patient until complete resolution is achieved. Many patients with a major depressive disorder (MDD) will improve with inadequate treatment, but remain encumbered by a smoldering, low-level dysthymia that, in itself, can severely restrict the patient's quality of life.
View details for PubMedID 11096781
A 28-year-old patient with acute lymphoblastic leukemia and neutropenia developed necrotizing enterocolitis and Clostridium septicum bacteremia, followed by rhabdomyolysis, skin rash, and acute neurologic changes. Numerous cortical leptomeningeal enhancements were present on head MRI. Meningeal and brain biopsy showed segmental, full-thickness lysis of smooth muscle cells of medium-sized meningeal vessels with overall preservation of the structure of the vessel wall.
View details for Web of Science ID A1997WC67600049
View details for PubMedID 9008531