Pharmacogenomics of mental illnesses: Do sex-specific differences matter?

Objectives: Genetic factors are extensively studied in respect to drug response in psychiatric disorders. Recent evidence suggests that action of reproductive steroid hormones in brain may also have a role. Methods: Sex-specific differences in terms of illness onset, duration, severity of symptoms and treatment response are well documented. It is believed they result from different brain morphology and function between sexes, factors being highly influenced by sex hormones. Results: The synergistic effects of the genetic background and potential prenatal stressors may influence the processes of sexual brain maturation, the most vulnerable period for developing susceptibility for psychiatric disorders. A resulting neuroendocrine dysfunction implies inadequate response of brain structures to pubertal flow of circulating sex hormones. Conclusion: Steroid sex hormones, at least estrogen, are major parts of the communication system in the brain. For that reason, estrogen receptors could be attractive targets in development of new treatment strategies. Potential benefits from compounds mimicking estrogen should be also considered in clinical practice.