Evidence suggests sex differences in schizophrenia reflect differences in both neurodevelopmental processes and social effects on disease risk and course. Male:female incidence approximates 1.4:1 but at older onset women predominate. Prevalence differences appear smaller. Men have poorer premorbid adjustment and present with worse negative and less depressive symptoms than women, which may explain their worse medium term outcome according to a range of measures. Substance abuse is a predominantly male activity in this group, as elsewhere. Findings of sex differences in brain morphology are inconsistent but occur in areas that normally show sexual dimorphism, implying that the same factors are important drivers of sex differences in both normal neurodevelopmental processes and those associated with schizophrenia. There are sex differences in antipsychotic responses but sex-specific endocrine effects on illness and response to antipsychotics are potentially complex. Oestrogen's role as an adjunctive medication is not yet clear due to methodological differences between the few randomized controlled trials. Services that are sensitive to differences in gender can better meet their patients' specific needs and potentially improve outcome.

Sex differences in schizophrenia

Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones.

Prenatal endocrine influences on sexual orientation and on sexually differentiated childhood behavior.

More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite its high prevalence, PCOS and its accompanying morbidities are likely underdiagnosed, averaging > 2 years and 3 physicians before women are diagnosed. Although it has been intensively researched, the underlying cause(s) of PCOS have yet to be defined. In order to understand PCOS pathophysiology, its developmental origins, and how to predict and prevent PCOS onset, there is an urgent need for safe and effective markers and treatments. In this review, we detail which animal models are more suitable for contributing to our understanding of the etiology and pathophysiology of PCOS. We summarize and highlight advantages and limitations of hormonal or genetic manipulation of animal models, as well as of naturally occurring PCOS-like females.

Animal models to understand the etiology and pathophysiology of polycystic ovary syndrome.

At a population level, women and men differ in a wide variety of behavioral traits and in the probabilities of developing certain mental disorders. Some of these sex differences may be related to sexual dimorphism in brain structure, as it emerges during prenatal and post-natal development. Here, I provide a brief overview of the sex-chromosome-specific pathways that underlie sexual dimorphisms in general, describe the most common brain phenotypes derived in vivo with magnetic resonance imaging, discuss the challenges in interpreting these phenotypes vis-a-vis the underlying neurobiology, and, finally, review the known sex differences in brain structure from birth, through adolescence, to adulthood.

Sex differences in the human brain: a developmental perspective.

Effects of prenatal androgens on rhesus monkeys: A model system to explore the organizational hypothesis in primates

The mission of the National Institute of Mental Health is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. In consultation with a broad range of experts, the NIMH has identified a set of priorities for stress biology research aimed squarely at creating the basic and clinical knowledge bases for reducing and alleviating mental health burden across the lifespan. Here, we discuss these priority areas in stress biology research, which include: understanding the heterogeneity of stressors and outcomes; refining and expanding the experimental systems used to study stress and its effects; embracing and exploiting the complexity of the stress response; and prioritizing translational studies that seek to test mechanistic hypotheses in human beings. We emphasize the challenge of establishing mechanistic links across levels of analysis to explain how and when specific and diverse stressors lead to enduring changes in neural systems and produce lasting functional deficits in mental health relevant behaviors. An improved understanding of mechanisms underlying stress responses and the functional consequences of stress can and will speed translation from basic research to predictive markers of risk and to improved, personalized interventions for mental illness.

Julia L. Zehr

Papers

Effects of prenatal androgens on rhesus monkeys: A model system to explore the organizational hypothesis in primates

Priorities in stress research: a view from the U.S. National Institute of Mental Health