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Biological sex differences relevant to mental health 

Biological sex differences relevant to mental health
Biological sex differences relevant to mental health

Peter Fitzgerald

and Timothy G. Dinan

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date: 23 January 2022

Scientific interest in the effects of the female sex steroids on modulating mood and behaviour stems largely in the modern era from the well-recognized sex differences found in certain psychiatric disorders.

The finding across many cultures and ethnic backgrounds from large epidemiological studies that women have twice the prevalence rate for depression as men, that this only becomes apparent after the onset of puberty, and that after the menopause rates return to near parity between the sexes, is a strong finding implicating a role for female gonadal hormones in playing an active part in such discrepancy. Further epidemiological evidence for sex steroids' capability to impact on mood and behaviour comes from the high rate of mood disturbance and psychosis seen in the postpartum period, a time of dramatic and rapid change in gonadal steroid secretion, in addition to the occurrence of a discrete menstrual cycle-related mood disorder (the premenstrual or late luteal phase dysphoric disorder), for which removal of the ovaries has been noted to be curative. Some conditions which may not be associated with a sex difference in lifetime prevalence rates are nevertheless associated with marked differences in course or outcome between the sexes, such as the later age of onset of schizophrenia in females, who generally manifest a less severe disorder which is more responsive to treatment, and who display a second peak onset around the time of the menopause, all suggestive of a somewhat protective role for gonadal steroids in this disorder.

How do gonadal steroids have such widespread effects on the brain so as to explain these sex differences? While current knowledge is far from complete on this issue, this chapter will outline some key structural and functional differences between a female and male brain which arise due to the differential actions of the gonadal steroids. In particular, those central structures and systems which are believed to play an integral role in the psychiatric disorders for which a marked sex difference exists will be focused upon, including the limbic system, the various neurotransmitter systems such as serotonin, noradrenaline, and dopamine, and finally the neuroendocrine system involved in the stress response, the hypothalamic–pituitary–adrenal axis.

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