Sex differences in stress-related disorders: Major depressive disorder, bipolar disorder, and posttraumatic stress disorder.

Stress-related disorders, such as mood disorders and posttraumatic stress disorder (PTSD), are more common in women than in men. This sex difference is at least partly due to the organizing effect of sex steroids during intrauterine development, while activating or inhibiting effects of circulating sex hormones in the postnatal period and adulthood also play a role. Such effects result in structural and functional changes in neuronal networks, neurotransmitters, and neuropeptides, which make the arousal- and stress-related brain systems more vulnerable to environmental stressful events in women. Certain brainstem nuclei, the amygdala, habenula, prefrontal cortex, and hypothalamus are important hubs in the stress-related neuronal network. Various hypothalamic nuclei play a central role in this sexually dimorphic network. This concerns not only the hypothalamus-pituitary-adrenal axis (HPA-axis), which integrates the neuro-endocrine-immune responses to stress, but also other hypothalamic nuclei and systems that play a key role in the symptoms of mood disorders, such as disordered day-night rhythm, lack of reward feelings, disturbed eating and sex, and disturbed cognitive functions. The present chapter focuses on the structural and functional sex differences that are present in the stress-related brain systems in mood disorders and PTSD, placing the HPA-axis in the center. The individual differences in the vulnerability of the discussed systems, caused by genetic and epigenetic developmental factors warrant further research to develop tailor-made therapeutic strategies.