The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Examples of male-biased conditions include early-onset disorders that involve some kind of neurodevelopmental impairment, such as autism, attention deficit/hyperactivity disorder, conduct disorder, specific language impairment, Tourette syndrome, dyslexia, or schizophrenia; examples of female-biased conditions include emotional disorders such as depression, anxiety disorder, and anorexia nervosa, which usually start during puberty or later in life. Factors influencing the relationships between brain development and function and sex may help to understand the differences between males and females in terms of risk or resilience factors to brain diseases.
In this issue, in her extensive review for the State of the Art article, Margaret McCarthy highlights the biological foundations of sex differences in the brain and their potential role in male and female differences in terms of vulnerability to neuropsychiatric disorders. For example, females have an approximately twofold increased risk for post-traumatic stress disorder.
Teniel Ramikie and Kerry Ressler have recently shown that pituitary adenylate cyclase-activating peptide (PACAP) and its receptor are critical mediators of abnormal processes after psychological trauma. Furthermore, this pathway is regulated by both estrogen and stress modulation.
Finally, Tracy Bale has focused her interest on the placenta. Perinatal insults are associated with an increased neurodevelopmental disease risk, and males are more vulnerable than females. Understanding the sex-specific molecular mechanisms involved in transplacental signals that impact brain development is key to improving our knowledge on sex bias in neurodevelopmental disorders such as autism, dyslexia, mental retardation or attention deficit/hyperactivity disorder.