Human Brain Development Implications for Maladies of the Male Mind

As you work through the chapters in this book it will become very clear that since the beginning of the ‘decade of the brain’ in 1990 we have made considerable progress in understanding how the brain works and the way that it develops across the lifespan. We have also made significant progress in understanding the genetic and environmental factors that contribute to the development of mental health problems. We still, however, struggle to develop new and innovative treatments and therapies and in our understanding of what works for whom in what circumstances – more recently labelled precision or personalized medicine. There are, of course, many factors that contribute to this lack of concrete progress. Psychiatric disorders are complex and heterogeneous across several levels of analysis: phenotypically, with co-morbidity being the rule rather than the exception; aetiologically, with a complex genetic architecture based on different types of genetic variants and gene–environment interplay and diverse brain alterations. Also, as there is no stable, agreed-upon, and biologically valid construct for any of the recognized psychiatric disorders, the current taxonomy provides an unclear basis for informed biological research. Attempts to define biologically homogeneous subtypes (‘biotypes’) or pathophysiological dimensions of psychiatric disorders are under way but have yet to deliver (Feczko et al., 2019). From another angle, enormous scientific challenges are still presented by the complexity of the brain’s architecture and physiology, our far from complete understanding of how these change across development, and the relationships between structure and function and between cognition and behaviour/symptoms. These continue to present enormous scientific challenges. Sex is an often unrecognized but essential variable in this whole picture. There are sex differences in prevalence for most psychiatric disorders. Being male is a significant risk for the development of neurodevelopmental and neuropsychiatric disorders (e.g. schizophrenia, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), Tourette’s disorder, and intellectual disability (ID)). While being female appears to afford some degree of protection against these common disorders, it increases risk, at least after puberty, for depression and eating disorders. A discussion of these sex differences forms the core of this book. In this opening chapter we focus on sex differences in brain development. While our understanding of these differences is far from complete, the hope is that, in time, knowledge of the biological origins and functional consequences of these risk and protective factors will generate novel therapeutic targets and approaches for prevention and intervention. We focus on two main lines of evidence that arise from human neuroimaging studies on the one hand and animal models on the other. Animal studies are particularly important in this context not only because they deliver several advantages in experimental design that are not possible in human studies but also because it is possible in animal models to separate sex from gender. In humans, gender is a complex construct that is based on a combination of our own and societal perception of our sex (see Chapter 7). Interestingly it is only in the last 60 years that it has been accepted that the brain plays an important role in determining sex differences in human behaviours. Up until this time it was generally accepted that it was the somatic characteristics and differences between males and females (i.e. their differing genitalia and secondary sexual characteristics) that led to their characteristic sexual behaviours. This idea was convincingly challenged in 1959 when Phoenix and colleagues published a seminal study demonstrating that, when pregnant guinea pigs were treated with testosterone, their female offspring – when adults – showed a copulatory pattern of males despite not having a penis (Phoenix et al., 1959). Sex differences between male and female embryos can be detected as soon as the second day following