Tilley Black (clamhandle5)

Sex differences are observed at many distinct biologic levels, such as in the anatomy and functioning of the brain, behavior, and susceptibility to neuropsychiatric disorders. Previously, these differences were believed to entirely result from the secretion of gonadal hormones; however, recent research has demonstrated that differences are also the consequence of direct or nonhormonal effects of genes located on the sex chromosomes. This chapter reviews the four core genotype model that separates the effects of hormones and sex chromosomes and highlights a few genes that are believed to be partly responsible for sex dimorphism of the brain, in particular, the Sry gene. Genetics of the brain's neurochemistry is discussed and the susceptibility to certain neurologic and psychiatric disorders is reviewed. Lastly, we discuss the sex-specific genetic contribution in disorders of sexual development. The precise molecular mechanisms underlying these differences are currently not entirely known. An increased knowledge and understanding of the role of candidate genes will undeniably be of great aid in elucidating the molecular basis of sex-biased disorders and potentially allow for more sex-specific therapies.The central noradrenergic system comprises multiple brainstem nuclei whose cells synthesize and release the catecholamine transmitter norepinephrine (NE). The largest of these nuclei is the pontine locus coeruleus (LC), which innervates the vast majority of the forebrain. NE interacts with a number of pre- and postsynaptically expressed G protein-coupled receptors to affect a wide array of functions, including sensory signal processing, waking and arousal, stress responsiveness, mood, attention, and memory. Given the myriad functions ascribed to the locus coeruleus-noradrenergic (LC-NE) system, it is unsurprising that it is implicated in many disease states, including various mood, cognitive, neuropsychiatric, and neurodegenerative diseases. The LC-NE system is also notably sexually dimorphic with regard to its morphologic and anatomical features as well as how it responds to the peptide transmitter corticotropin releasing hormone (CRH), a major mediator of the central stress response. The sex-biased morphology and signaling that is observed in the LC could then be considered a potential contributor to the differential prevalence of various diseases between men and women. This chapter summarizes the primary differences between the male and female LC, based primarily on preclinical observations and how these disparities may relate to differential diagnoses of several diseases between men and women.Sex differences are present in psychiatric disorders associated with disrupted dopamine function, and thus, sex differences in dopamine neurobiology may underlie these clinical disparities. In this chapter, we review sex differences in the dopaminergic system with a focus on substance use disorders, especially tobacco smoking, as our exemplar disorder. This chapter is organized into five sections describing sex differences in the dopaminergic system (1) neurobiology, (2) role of sex hormones, (3) genetic underpinnings, (4) cognitive function, and (5) influence on addiction. In each section, we provide an overview of the topic area, summarize sex differences identified to date, highlight addiction research, especially clinical neuroimaging studies, and suggest avenues for future research.In the last two decades, the 60 years old view that in utero exposure to testosterone irreversibly masculinizes the brain of males away from a default female form has been replaced by a complex scenario according to which sex affects the brains of both females and males via multiple mechanisms, which are susceptible to internal and external factors. These observations led to the "mosaic" hypothesis-the expectation that the degree of "maleness"/"femaleness" of different features within a single brain would not be internally consistent. Following a short r