N. Müller

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment

The stress hormone–regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor–regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant–dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

Disability and quality of life in pure and comorbid social phobia. Findings from a controlled study

Social phobia is increasingly recognized as a prevalent and socially impairing mental disorder. However, little data is available regarding the general and disease-specific impairments and disabilities associated with social phobia. Furthermore, most studies have not controlled for the confounding effects of comorbid conditions. This study investigates: (a) the generic quality of life; (b) work productivity; and, (c) various other disorder-specific social impairments in current cases with pure (n = 65), comorbid (n = 51) and subthreshold (n = 34) DSM-IV social phobia as compared to controls with no social phobia (subjects with a history of herpes infections). Social phobia cases reported a mean illness duration of 22.9 years with onset in childhood or adolescence. Current quality of life, as assessed by the SF-36, was significantly reduced in all social phobia groups, particularly in the scales measuring vitality, general health, mental health, role limitations due to emotional health, and social functioning. Comorbid cases revealed more severe reductions than pure and subthreshold social phobics. Findings from the Liebowitz self-rated disability scale indicated that: (a) social phobia affects most areas of life, but in particular education, career, and romantic relationship; (b) the presence of past and current comorbid conditions increases the frequency of disease-specific impairments; and, (c) subthreshold social phobia revealed slightly lower overall impairments than comorbid social phobics. Past week work productivity of social phobics was significantly diminished as indicated by: (a) a three-fold higher rate of unemployed cases; (b) elevated rates of work hours missed due to social phobia problems; and, (c) a reduced work performance. Overall, these findings underline that social phobia in our sample of adults, whether comorbid, subthreshold, or pure was a persisting and impairing condition, resulting in considerable subjective suffering and negative impact on work performance and social relationships. The current disabilities and impairments were usually less pronounced than in the past, presumably due to adaptive behaviors in life style of the respondents. Data also confirmed that social phobia is poorly recognized and rarely treated by the mental health system.