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It is commonly – but wrongly – assumed that there are no importantdifferences between the clinical presentations of major depressive disorderand bipolar depression. Here we compare clinical course variables anddepressive symptom profiles in a large sample of individuals with majordepressive disorder (n=593) and bipolar disorder(n=443). Clinical characteristics associated with abipolar course included the presence of psychosis, diurnal mood variationand hypersomnia during depressive episodes, and a greater number of shorterdepressive episodes. Such features should alert a clinician to a possiblebipolar course. This is important because optimal management is not the samefor bipolar and unipolar depression.

It is commonly – but wrongly – assumed that there are no important differences between the clinical presentations of major depressive disorder and bipolar depression. Here we compare clinical course variables and depressive symptom profiles in a large sample of individuals with major depressive disorder (n=593) and bipolar disorder (n=443). Clinical characteristics associated with a bipolar course included the presence of psychosis, diurnal mood variation and hypersomnia during depressive episodes, and a greater number of shorter depressive episodes. Such features should alert a clinician to a possible bipolar course. This is important because optimal management is not the same for bipolar and unipolar depression.

Brain-derived neurotrophic factor (BDNF) influences neuronal survival, proliferation and plasticity. Three family-based studies have shown association of the common Valine (Val) allele of the Val66Met polymorphism of the BDNF gene with susceptibility to bipolar disorder. To replicate this finding. We genotyped the Val66Met polymorphism in our UK White bipolar case-control sample (n=3062). We found no overall evidence of allele or genotype association. However, we found association with disease status in the subset of 131 individuals that had experienced rapid cycling at some time (P=0.004). We found a similar association on re-analysis of our previously reported family-based association sample (P < 0.03, one-tailed test). Variation at the Val66Met polymorphism of BDNF does not play a major role in influencing susceptibility to bipolar disorder as a whole, but is associated with susceptibility to the rapid-cycling subset of the disorder.

Abnormalities of cognitive style in bipolar disorder are of both clinical and theoretical importance. To compare cognitive style in people with affective disorders and in healthy controls. Self-rated questionnaires were administered to 118 individuals with bipolar I disorder, 265 with unipolar major recurrent depression and 268 healthy controls. Those with affective disorder were also interviewed using the Schedules for Clinical Assessment in Neuropsychiatry and case notes were reviewed. Those with bipolar disorder and those with unipolar depression demonstrated different patterns of cognitive style from controls; negative self-esteem best discriminated between those with affective disorders and controls; measures of cognitive style were substantially affected by current levels of depressive symptomatology; patterns of cognitive style were similar in bipolar and unipolar disorder when current mental state was taken into account. Those with affective disorder significantly differed from controls on measures of cognitive style but there were no differences between unipolar and bipolar disorders when current mental state was taken into account.