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.

Background. The German National Health Interview and Examination Survey (GHS) is the first government mandated nationwide study to investigate jointly the prevalence of somatic and mental disorders within one study in the general adult population in Germany. This paper reports results from its Mental Health Supplement (GHS-MHS) on 4-week 12-month, and selected lifetime prevalence of a broad range of DSM-IV mental disorders, their co-morbidity and correlates in the community.Methods. The sample of the GHS-MHS (n=4181; multistage stratified random sample drawn from population registries ; conditional response rate : 87 . 6 %) can be regarded as representative for the German population aged 18-65. Diagnoses are based on fully structured computer assisted clinical interviews (M-CIDI), conducted by clinically trained interviewers.Results. 12-month prevalence for any DSM-IV study disorder is 31 % (lifetime : 43 % ; 4-week : 20 %) with anxiety disorders, mood disorders and somatoform syndromes being the most frequent diagnoses. Retrospective age of onset information reveals that most disorders begin early in life. Comorbidity rates among mental disorders range from 44 % to 94%. Correlates of increased rates of mental disorders and co-morbidity were : female gender (except for substance disorders), not being married, low social class, and poor somatic health status. Health care utilization for mental disorders depended on co-morbidity (30 % in 'pure', 76 % in highly co-morbid cases) and varied from 33% for substance use disorders to 75 % for panic disorder.Conclusions. Results confirm and extend results from other national studies using the same assessment instruments with regard to prevalence, co-morbidity and sociodemographic correlates, covering a broader range of DSM-IV disorders [i.e. somatoform disorders, all anxiety disorders (except PTSD), mental disorders due to substance or general medical factor, eating disorders]. Intervention rates were higher than in previous studies, yet still low overall.

The structure and content of the Munich-Composite International Diagnostic Interview (M-CIDI) for the assessment of DSM-IV symptoms, syndromes, and diagnoses is described along with findings from a test-retest reliability study. A sample of 60 community respondents were interviewed twice independently by trained interviewers with an average time interval of 38 days between investigations. Test-retest reliability was good for almost all specific DSM-IV core symptom questions and disorders examined, with kappa values ranging from fair for two diagnoses--bulimia (kappa 0.55) and generalized anxiety disorder (kappa 0.45)--to excellent (kappa above 0.72) for all other anxiety disorders and alcohol use disorders. Test-retest reliability for age of onset and time-related questions was fairly consistently high (intra-class correlation values of 0.79 or above), with one notable exception: the assessment of disorders with onset before puberty. We concluded that the M-CIDI is acceptable for respondents, efficient in terms of time needed for and ease of administration, and reliable in terms of consistency of findings over time periods of at least 1 month.

Major depression in parents increases the overall risk in offspring for onset of depressive and other mental disorders and influences patterns of the natural course of depression in the early stages of manifestation.