Convergent animal and human evidence suggests the activin/inhibin pathway to be involved in antidepressant response.

Despite the overt need for improved treatment modalities in depression, efforts to develop conceptually novel antidepressants have been relatively unsuccessful so far. Here we present a translational approach combining results from hypothesis-free animal experiments with data from a genetic association study in depression. Comparing genes regulated by chronic paroxetine treatment in the mouse hippocampus with genes showing nominally significant association with antidepressant treatment response in two pharmacogenetic studies, the activin pathway was the only one to show this dual pattern of association and therefore selected as a candidate.

High susceptibility to chronic social stress is associated with a depression-like phenotype.

Chronic stress is a key risk factor for a variety of diseases, including depression. There is a large degree of individual variation in the ability to recover successfully from a chronic stress exposure, but the determinants of this individual stress susceptibility are still poorly understood. We recently developed a novel mouse paradigm for chronic social stress during adolescence, which closely mimics the human condition of chronic social stress in respect to construct, face and predictive validity.

Chronic social stress during adolescence induces cognitive impairment in aged mice.

Age-related cognitive decline is one of the major aspects that impede successful aging in humans. Environmental factors, such as chronic stress, can accelerate or aggravate cognitive deficits during aging. While there is abundant evidence that chronic stress directly affects cognitive performance, the lasting consequences of stress exposures during vulnerable developmental time windows are largely unknown.

A single episode of restraint stress regulates central corticotrophin- releasing hormone receptor expression and binding in specific areas of the mouse brain.

The importance of restraining stress-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) system within tolerable limits requires efficient mechanisms for feedback inhibition. Recently, central corticotrophin-releasing hormone (CRH) receptor type 1 (CRHR1) has been shown to mediate HPA system feedback inhibition. To date, most of the data regarding stress-associated expression changes of CRHR1 and CRHR2 mRNA and their ligand CRH have been generated in rats.

Postnatal glucocorticoid excess due to pituitary glucocorticoid receptor deficiency: differential short- and long-term consequences.

A tight regulation of hypothalamic-pituitary-adrenal (HPA) axis activity is essential for successful adaptation to stressful stimuli. Disruption of normal HPA axis development is a main risk factor for diseases such as posttraumatic stress disorder or depression, but the molecular mechanisms that lead to these long-term consequences are poorly understood. Here, we test the hypothesis that the pituitary glucocorticoid receptor (GR) is involved in regulating HPA axis function in neonatal and adult animals.