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.

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While a correlation of dosage and effect could be shown with Quetiapin, inter- and intraindividual differences could be observed. Drug monitoring therefore seems useful in clinical setting and is recommended.

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In the treatment of affective and schizophrenic psychosis, modern atypical antipsychotic agents and newer antidepressive agents recently have increasingly been used. In this prospective naturalistic study, patients were examined who had previously been treated psychopharmaceutically for a schizophrenic (n = 52) or depressive (n = 38) disorder and were readmitted in a psychiatric emergency clinic. While Serum levels were examined major interest was to find out similarities or differences in the drug compliance of schizophrenic and depressive patients before rehospitalization.