Why, in Neuroscience and Neuropsychopharmacology, are sex differences important?

Prevalence and symptoms of most #psychiatric and #neurological disorders differ in men and women and there is substantial evidence that their neurobiological basis and treatment also differ by sex. Sex differences are present in neuroendocrine functions, stress response, cognitive processes, as well as in neuropsychiatric, neurodegenerative, neurodevelopmental disorders and their pharmacological treatments.

One of the most common areas of research for sex differences has been the investigation of steroid hormones and the hypothalamic-pituitary-gonadal (HPG), or adrenal (HPA) systems, where estradiol and glucocorticoids were the focus of most of this research to date. For decades, the usual suspects for steroid action and sex difference in the central nervous system were limited to the hypothalamus, however, it became clear that steroids affect many brain regions.


The impact of sex differences on cognition and how environmental factors affect cognitive capacities is highlighted by studies. Using a rodent model, Gogos et al., showed that adult males show deficits in spatial working memory. But there were no significant effects on females. Moreover, Espinosa-Garcia et al., showed that everyday diet changes may impact cognition differently in males and females. Male rats with a hypercaloric diet have impairments in learning and memory compared to females, but the long-term memory impairment is evident in both sexes.


The impact of brain injury comes out as an area where more research on sex differences is needed. But is now accepted that the impact of brain injury and the following regeneration/degeneration processes are sexually differentiated in adults, mostly due to estrogens and progesterone. Current evidence suggests that sex differences also occur early on, prior puberty.

Sex differences exist in stress-related disorders, affective disorders, dementia and substance abuse. These neuropsychiatric disorders share neurobiological mechanisms and sex-differentiated features, including genetic, anatomical, molecular, and hormonal effects that influence the prevalence, the symptomatology, the recovery/relapse, and response to treatment. The stress of isolation via single housing has pervasive effects on cognition, depressive‐like behaviour, and neuroplasticity‐related signalling in adult male and female mice, although in modest sex-dependent ways. Studies have shown that male mice are more vulnerable to stress-induced hyperthermia than female mice. Neuronal circuits that underlie fear, arousal, anxiety, learning/memory, reward, and emotion are also sex-differentiated and contribute to sex differences in neuropsychiatric disorders and neuropsychopharmacology


Medications and drugs of abuse also show marked sex differences in neuroscience research. Male animals showed enhanced locomotor effects following a low dose of morphine, while the effect in females was not apparent until high doses of morphine were used.


In conclusion, sex differences matter and are essential to further the fields of neuroscience and neuropsychopharmacology. We should increase awareness of the importance of sex differences in neuroscience and beyond, throughout life and reproductive states to improve our understanding of brain function, neuropsychiatric disorders and treatment efficacy.

Source: Sex Matters in Neuroscience and Neuropsychopharmacology
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