The brains of males and females, men and women, are different, that is a fact. What is debated is how different and how important are those differences. Sex differences in the brain are determined by genetics, hormones, and experience, which in humans includes culture, society, and parental and peer expectations. The importance of nonbiological variables to sex differences in humans is paramount, making it difficult if not impossible to parse out those contributions that are truly biological. The study of animals provides us the opportunity to understand the magnitude and scope of biologically based sex differences in the brain, and understanding the cellular mechanisms provides us insight into novel sources of brain plasticity. Many sex differences are established during a developmental sensitive window by differences in the hormonal milieu of males versus females. The neonatal testis produces large amounts of testosterone which gains access to the brain and is further metabolized into active androgens and estrogens which modify brain development. Major parameters that are influenced by hormones include neurogenesis, cell death, neurochemical phenotype, axonal and dendritic growth, and synaptogenesis. Variance in these parameters results in sex differences in the size of particular brain regions, the projections between brain regions, and the number and type of synapses within particular brain regions. The cellular mechanisms are both region and endpoint specific and invoke many surprising systems such as prostaglandins, endocannabinoids, and cell death proteins. Epigenetic modifications to the genome both establish and maintain sex differences in the brain and behavior. By understanding when, why, and how sex differences in the brain are established, we may also learn the source of strong gender biases in the relative risk and severity of numerous neurological diseases and disorders of mental health. Boys are much more likely to be diagnosed with autism spectrum or attention and hyperactivity disorders, as well as speech and language deficits, compared to girls. By contrast, women are more likely to suffer from affective disorders, such as depression, anxiety, compulsion, and eating disorders and more likely to experience autoimmune and neurodegenerative disorders. Schizophrenia with an early onset is more common in males but a late-onset version is markedly more frequent in females. Male biased disorders have origins in development while female biased disorders are almost exclusively post-puberty. This remarkable shift in disease risk demands our attention. Novel insights into the biological origins of disease are also gained by comparing and contrasting the same processes in different sexes.

Margaret M. McCarthy, University of Maryland School of Medicine
Dr. Margaret M. McCarthy is a professor of pharmacology, physiology, and psychiatry, and the chair of the Department of Pharmacology at the University of Maryland School of Medicine in Baltimore. Dr. McCarthy's research focuses on the influence of steroid hormones on the developing brain. During perinatal life, there is a sensitive period for hormone exposure during which permanent cytoarchitectural changes are established. Males and females are exposed to different hormonal milieus, and this results in sex differences in the brain. These differences include alterations in the volumes of particular brain nuclei and patterns of synaptic connectivity. The mechanisms by which sexually dimorphic structures are formed in the brain remain poorly understood.

Dr. McCarthy received her PhD in behavioral and neural sciences from the Institute of Animal Behavior at Rutgers University in Newark, NJ in 1989. She then spent three years as a post-doctoral fellow at the Rockefeller University in New York, NY and one year as a National Research Council fellow at the National Institutes of Health, before joining the faculty at the University of Maryland. She is a member of multiple scientific societies, the current president of the Organization for the Study of Sex Differences, and an associate editor of the journal Hormones and Behavior.

Table of Contents
Preface
Introduction
Sex Differences in Brain and Behavior in Context
Sex Determination versus Sex Differentiation
Masculinization, Feminization, and Defeminization
Steroid Hormones are Potent Modulators of Brain Development
Sex Differences in the Brain are Established During a Developmental Sensitive Window
Sex Differences in Reproductive Physiology and Behavior are Coordinated
Steroids Influence Multiple Endpoints via Multiple Mechanisms to Organize the Brain
Cellular Mechanisms of Steroid-Mediated Organization of the Brain
Ultrasonic Vocalizations Differ in Neonatal Males and Females Because of a Gene Called FoxP2
Overcoming the Hegemony of Hormones: Genes Matter Too
Winged Messengers: Lessons from Birds and Flies
Sexual Differentiation of the Primate Brain
Sexual Differentiation of the Human Brain
Imaging Studies Give Insight Into Brain Sex Differences
Steroids and Human Brain Development
The Value of Understanding the Effect of Sex on the Developing Brain
Bibliography
Classic References
Author Biography