Epidemiological studies show low rates of diagnosed depression in men compared to women. At the same time, high rates of alcohol use disorders (AUDs) and completed suicide are found among men. These data suggest that a male-specific pattern for depression may exist that is linked to AUDs and suicidal behavior. To date, no underlying neuroendocrine model for this specific pattern of male depression has been suggested. In this paper, we integrate findings related to this specific pattern of depression with underlying steroid secretion patterns, polymorphisms, and methylation profiles of key genes in order to detail an original neuroendocrine model of male-specific depression. Low circulating levels of sex steroids seem to increase the vulnerability for male depression, while concomitant high levels of glucocorticoids further intensify this vulnerability. Interactions of hypothalamus–pituitary–gonadal (HPG) and hypothalamus–pituitary–adrenocortical (HPA) axis-related hormones seem to be highly relevant for a male-specific pattern of depression linked to AUDs and suicidal behavior. Moreover, genetic variants and the epigenetic profiles of the androgen receptor gene, well-known depression related genes, and HPA axis-related genes were shown to further interact with men’s steroid secretion and thus may further contribute to the proposed male-specific pattern for depression. This mini-review points out the multilevel interactions between the HPG and HPA axis for a male-specific pattern of depression linked to AUDs and suicidal behavior. An integration of multilevel interactions within the three-hit concept of vulnerability and resilience concludes the review.

In this study, we report the developmental, physical and psychiatric manifestations of 22q11.2 deletion syndrome (22q11.2DS) in a large Israeli cohort, and search for a possible association between preterm birth and the risk for psychotic disorders. The study population consisted of 128 individuals with 22q11.2DS (77 male, 51 female), aged 1-55 years (mean ± SD 12.9 ± 11.0). All subjects underwent a comprehensive medical evaluation. All subjects older than 5 years (n = 104) were also evaluated psychiatrically. Overall, we found rates of physical manifestations similar to those previously reported in the literature. Psychiatric disorders were very common among our study population, with psychotic disorders occurring in 16.3 % of the psychiatrically evaluated population. We found an association between the presence of psychotic disorders and preterm birth. Our results replicate and extend the findings of a previous work and suggest that the evolution of psychosis in 22q11.2DS is a neurodevelopmental process with early obstetric and medical precursors.

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