Lakshmi N. Yatham

Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis

Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta‐analysis. Bipolar Disord 2012: 14: 478–487.

Seasonal depression: The dual vulnerability hypothesis revisited

OBJECTIVEnIn DSM-IV, winter seasonal affective disorder (SAD) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer. However, other groups with winter depression have been identified, including patients with incomplete summer remission (ISR) and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet criteria for major depression). In this study, we compare the clinical characteristics of these three seasonal groups and their response to light therapy.nnnMETHODn558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a checklist at index assessment. A subset of patients (N=192) were treated with an open, 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning. Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50% improvement in scores.nnnRESULTSnThe rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family history of mood disorder were lowest in the sub-SAD group. The clinical response rates to light therapy were highest in the sub-SAD group (N=32, 78%), intermediate in the SAD group (N=113, 66%), and lowest in the ISR group (N=47, 51%).nnnLIMITATIONSnThis was a retrospective study of patients seen in a specialty clinic, although information was obtained in a standardized format. The light therapy trial had an open design so that placebo response could not be determined.nnnCONCLUSIONSnThere are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression. These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression.

Atypical depressive symptoms and clusters in unipolar and bipolar depression

In order to examine differences in the atypical symptoms of depression between unipolar and bipolar patients, we studied 109 depressed patients (79 unipolar and 30 bipolar subjects) diagnosed with DSM‐IV criteria. Patients were assessed using the Atypical Depression Diagnostic Scale (ADDS), a semi‐structured interview that rates mood reactivity and other atypical depressive symptoms. Although atypical depression was common in this sample (28% of cases with definite atypical depression), no differences were found between the unipolar and bipolar patients in either the atypical symptom profile or the prevalence of an atypical depression diagnosis. The interrelationships between the atypical symptoms were also examined using a hierarchical cluster analysis. A five‐cluster solution maximized differences between groups, with results suggesting that atypical depression may be a heterogeneous diagnosis.

Effects of rapid tryptophan depletion in patients with seasonal affective disorder in natural summer remission

BACKGROUNDnSerotonergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD) and the therapeutic effect of bright-light treatment. Previously, we showed that SAD patients, in clinical remission with light therapy during the winter, experienced transient depressive relapses after a rapid tryptophan depletion (RTD) technique, which results in decreased brain serotonin levels. The objective of this study was to investigate the effect of RTD in SAD patients who were in natural summer remission.nnnMETHODSnTwelve drug-free patients with SAD by DSM-IV criteria and 10 normal subjects participated in this double-blind, placebo-controlled, crossover study. SAD patients were in natural summer remission for at least 8 weeks. Behavioural ratings and plasma tryptophan levels were obtained before, and 5 h after, ingesting an amino acid (AA) mixture +/- tryptophan. Experimental RTD and control sessions were scheduled 1 week apart.nnnRESULTSnThe RTD session resulted in significant reduction in total and free plasma tryptophan levels compared to the control session. The behavioural data were analysed using repeated measures analysis of variance. This analysis found significant main effects of time (higher scores after AA ingestion) and diagnosis (higher scores in SAD patients), but no main effect of session or significant interaction effects between the three factors. Thus, there were no significant behavioural effects of RTD compared to the sham depletion control session.nnnCONCLUSIONSnThe summer remission experienced by SAD patients is not dependent on plasma tryptophan levels (and presumably brain serotonin function) in the same manner as that of remission after light therapy. These results conflict with those of other laboratories, perhaps because of differences in study samples.

Effects of Alpha-Methyl-Para-Tyrosine-Induced Catecholamine Depletion in Patients with Seasonal Affective Disorder in Summer Remission

Noradrenergic and dopaminergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD). We investigated the effects of catecholamine depletion using α-methyl-para-tyrosine (AMPT), an inhibitor of tyrosine hydroxylase, in patients with SAD in natural summer remission. Nine drug-free patients with SAD by DSM-IV criteria, in summer remission for at least eight weeks, completed a double-blind, crossover study. Behavioral ratings and serum HVA and MHPG levels were obtained for 3-day sessions during which patients took AMPT or an active control drug, diphenhydramine.The active AMPT session significantly reduced serum levels of HVA and MHPG compared with the control diphenhydramine session. The AMPT session resulted in higher depression ratings with all nine patients having significant clinical relapse, compared with two patients during the diphenhydramine session. All patients returned to baseline scores after drug discontinuation. Catecholamine depletion results in significant clinical relapse in patients with SAD in the untreated, summer-remitted state. AMPT-induced depressive relapse may be a trait marker for SAD, and/or brain catecholamines may play a direct role in the pathogenesis of SAD.