Philip B. Mitchell

Oxytocin Increases Gaze to the Eye Region of Human Faces

BACKGROUND In nonhuman mammals, oxytocin has a critical role in peer recognition and social approach behavior. In humans, oxytocin has been found to enhance trust and the ability to interpret the emotions of others. It has been suggested that oxytocin may enhance facial processing by increasing focus on the eye region of human faces. METHODS In a double-blind, randomized, placebo-controlled, between-subject design, we tracked the eye movements of 52 healthy male volunteers who were presented with 24 neutral human faces after intranasal administration of 24 IU oxytocin or placebo. RESULTS Participants given oxytocin showed an increased number of fixations and total gaze time toward the eye region compared with placebo participants. CONCLUSIONS Oxytocin increases gaze specifically toward the eye region of human faces. This may be one mechanism by which oxytocin enhances emotion recognition, interpersonal communication, and social approach behavior in humans. Findings suggest a possible role for oxytocin in the treatment of disorders characterized by eye-gaze avoidance and facial processing deficits.

Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression.

In 39 hospital inpatients with severe primary depressive disorders, we evaluated the relationships between subcortical hyperintensities on magnetic resonance imaging (MRI) and clinical features, neuropsychological impairment and response to standard therapies. Both white matter and gray nuclei lesions were associated with older age and the absence of a family history of affective disorder. White matter hyperintensities were also associated with onset of first affective episode after the age of 50 years and impaired psychomotor speed. Most importantly, the severity of white matter hyperintensities predicted a poorer response to treatment (r = -0.44, p < .01). Negative correlations of the same order were detected in those (n = 20) who received electroconvulsive therapy (r = -0.42, p = .06) and those (n = 19) who received pharmacotherapy alone (r = -.49, p < .05). This study provides preliminary evidence supporting the clinical and prognostic significance of extensive white matter hyperintensities in patients with severe depression.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis

Abstract Objective: To examine the association between trends in antidepressant prescribing and suicide rates in Australia for 1991-2000. Design: Analysis of databases of suicide and rates of antidepressant prescribing according to age and sex. Setting: Australian Bureau of Statistics data, sales data from the Australian pharmaceutical industry, prescribing data in general practice. Subjects: Men and women aged 15 years and over in 10 year age groups. Main outcome measures: Trends in suicide rates and trends in antidepressant prescribing. Association measured by Spearmans rank correlations. Results: While overall national rates of suicide did not fall significantly, incidence decreased in older men and women and increased in younger adults. In both men (rs=−0.91; P<0.01) and women (rs=−0.76; P<0.05) the higher the exposure to antidepressants the larger the decline in rate of suicide. Conclusions: Changes in suicide rates and exposure to antidepressants in Australia for 1991-2000 are significantly associated. This effect is most apparent in older age groups, in which rates of suicide decreased substantially in association with exposure to antidepressants. The increase in antidepressant prescribing may be a proxy marker for improved overall management of depression. If so, increased prescribing of selective serotonin reuptake inhibitors in general practice may have produced a quantifiable benefit in population mental health. What is already known on this topic There has been a substantial increase in antidepressant prescribing by general practitioners in Australia since the introduction of selective serotoin reuptake inhibitors in the early 1990s Previous studies have indicated an association between increased antidepressant prescribing and reduced suicide rate What this study adds In Australia the rate of suicide fell in older people, the age group most heavily exposed to antidepressants Most antidepressants are now prescribed by general practitioners The association may indicate the improved treatment of depression by general practitioners

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial {

BACKGROUND Preliminary evidence suggests transcranial direct current stimulation (tDCS) has antidepressant efficacy. AIMS To further investigate the efficacy of tDCS in a double-blind, sham-controlled trial (registered at www.clinicaltrials.gov: NCT00763230). METHOD Sixty-four participants with current depression received active or sham anodal tDCS to the left prefrontal cortex (2 mA, 15 sessions over 3 weeks), followed by a 3-week open-label active treatment phase. Mood and neuropsychological effects were assessed. RESULTS There was significantly greater improvement in mood after active than after sham treatment (P<0.05), although no difference in responder rates (13% in both groups). Attention and working memory improved after a single session of active but not sham tDCS (P<0.05). There was no decline in neuropsychological functioning after 3-6 weeks of active stimulation. One participant with bipolar disorder became hypomanic after active tDCS. CONCLUSIONS Findings confirm earlier reports of the antidepressant efficacy and safety of tDCS. Vigilance for mood switching is advised when administering tDCS to individuals with bipolar disorder.

A Randomized Controlled Trial of D-Cycloserine Enhancement of Exposure Therapy for Social Anxiety Disorder

BACKGROUND Pilot research has suggested that D-cycloserine (DCS) enhances treatment outcomes for anxiety disorders when employed as an adjunct to exposure therapy (ET). The aim of this study was to determine whether 50 mg of DCS enhances ET for social anxiety disorder (SAD) according to a comprehensive set of symptom and life impairment measures. METHODS In a randomized double-blind placebo-controlled trial, we administered 50 mg of DCS or placebo in combination with ET to 56 participants who met primary diagnosis for SAD. RESULTS Participants administered DCS reported greater improvement on measures of symptom severity, dysfunctional cognitions, and life-impairment from SAD in comparison with placebo-treated participants. Effect sizes were mostly in the medium range. Results also indicated that the amount of adaptive learning about ones ability to give speeches in front of an audience interacted with DCS to enhance treatment outcome. CONCLUSIONS This study shows that the administration of DCS before ET enhances treatment outcomes for SAD. Results also provide the first preliminary evidence to suggest that DCS moderates the relationship between a reduction in negative appraisals about ones speech performance and improvement in overall SAD symptoms.

The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders.

OBJECTIVES Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. METHODS Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. RESULTS Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. CONCLUSION Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder

In humans, oxytocin nasal administration reduces social-threat perception and improves processes involved in communication and the encoding of positive social cues. The aim of this study was to determine whether oxytocin given as an adjunct to exposure therapy improves treatment for social anxiety disorder (SAD) as indicated by a comprehensive set of symptom outcome measures. In a randomized, double-blind, placebo-controlled trial, we administered 24 IU of oxytocin or a placebo in combination with exposure therapy to twenty-five participants who met primary diagnosis for SAD. Participants administered with oxytocin showed improved positive evaluations of appearance and speech performance as exposure treatment sessions progressed. These effects did not generalize to improve overall treatment outcome from exposure therapy. Participants who received oxytocin or placebo reported similar levels of symptom reduction following treatment across symptom severity, dysfunctional cognition, and life-impairment measures. This study shows that the administration of oxytocin improves mental representations of self, following exposure therapy. These effects may be either short term or situation specific. Future research is now needed to determine whether oxytocin can enhance treatment outcomes for SAD when used with greater frequency, with a wider variety of social learning experiences, and in conjunction with interventions that more specifically target change in broader dysfunctional cognitions.

Prevalence and correlates of DSM-IV major depression in an Australian national survey

BACKGROUND Community surveys have reported prevalence of depressive disorders in adult populations since the 1970s. Until recently, no epidemiological studies of the same magnitude have been conducted to provide a profile of the adult population in Australia. This study examines the current (30-day) prevalence and correlates of major depression in the adult Australian population using data from the National Survey of Mental Health and Well-being, and compares the results with other national studies. METHODS Data were derived from a national sample of 10,641 people 18-75+ years of age surveyed using the computerised version of the Composite International Diagnostic Interview Version 2.1. RESULTS The overall weighted prevalence of current (30-day) major depression was 3.2% with the highest rate (5.2%) being found in females in mid life. This rate is between those of the USA National Comorbidity Survey and the Epidemiological Catchment Area study, and similar to the British Psychiatric Morbidity Survey. The strongest correlates for reported current major depression include being unemployed, smoking, having a medical condition, followed by being in mid life, previously married, and female. Living with a partner and drinking 1 to 2 glasses of alcohol per day were least correlated. Some correlates of major depression relate to social disadvantage and lifestyle issues. LIMITATIONS The study design does not allow definition of direction of causality. CONCLUSION Lowering the prevalence rate of major depression will require close attention to public health approaches to address the relationships between smoking, social isolation, poor health, mood and physical well-being. The best focus for this approach may be primary care settings.

A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression

Two recent sham-controlled studies found that transcranial direct current stimulation (tDCS) was an effective treatment for depression. As tDCS is painless, relatively safe and inexpensive, its efficacy in treating depression warrants further investigation. This double-blind, randomized study tested tDCS at the same stimulation parameters as a previous positive study (1 mA current strength, five treatment sessions, active or sham, given on alternate days) in 40 depressed participants. Anodal stimulation was centred over the left dorsolateral prefrontal cortex, with the cathode placed on the lateral aspect of the contralateral orbit. tDCS was continued up to a total of ten active sessions per participant. Mood outcomes were measured by psychiatrist raters blind to treatment condition using the Montgomery-Asberg and other depression rating scales. Psychomotor speed was assessed immediately before and after a single tDCS session and attention, frontal executive function, working memory and verbal learning were assessed after each group of five sessions. Overall depression scores improved significantly over ten tDCS treatments, but there was no between-group difference in the five-session, sham-controlled phase. tDCS was found to be safe, with no adverse effects on neuropsychological function, and only minor side-effects. It is recommended that the efficacy of tDCS in depression be further evaluated over a longer treatment period, using enhanced stimulation parameters.