Purpose of review: The association between endocrine and neuropsychiatric disorders was established long ago, with solid evidence. According to a multidimensional model of mental disorders, one can conceptualize sex and gender-related endocrinological dysfunctions as a cluster of risk factors included in the biological determinants of those disorders.
Recent findings: Gender and sexual dimorphism in brain functions and pathways may have a main impact and synergistic effects on health differences in both men and women. To explain these differences, hormonal reactivity to stress, sex hormones and gene-environment interactions are among the most researched mechanisms.
Summary: In this paper, we review updated data on sex and gender differences in stress reactivity, concerning the hypothalamic-pituitary-adrenal axis, endocrinological dysfunction and vulnerability to major psychiatric disorders, in a stress-diathesis approach. Mainly schizophrenia and affective disorders are discussed, according to recent investigation, in terms of early determinants of stress reactivity, the interplay of genetic expression and gender role, their responsibility in biological modulation and their hypothetical contribution to explain gender differences in prevalence and clinical aspects of mental disorders.