Sex Differences in Neural Correlates of ADHD Among Children and Adolescents

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2021-05

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The Ohio State University

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Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a debilitating psychiatric condition characterized by symptoms of hyperactivity, impulsivity, and inattention. It exerts negative effects on persons affected, on their families, and within broader communities. The hyperactive-impulsive (HI) and combined (C) presentations portend development of both externalizing and internalizing psychopathology across the lifespan—trajectories of which often differ by sex. Both girls and boys with ADHD in childhood are vulnerable to developing oppositional defiant disorder (ODD) in childhood. Thereafter, however, males are vulnerable to conduct disorder (CD), substance use, and antisocial personality disorder (ASPD), whereas females are vulnerable to self-harm, suicidal behaviors, substance use, and borderline personality disorder (BPD). These trajectories can be explained in part through the lens of ontogenic process models, which consider how genetic, neural, and other biological vulnerabilities interact with environmental risk factors over time to alter neurodevelopment and canalize problematic behavior. This review details dysfunction in dopaminergic (DA) and serotonergic (5-HT) and noradrenergic (NA) systems that may underlie certain sex differences in ADHD and its progression. Gaps in knowledge are identified that should guide future research on developing and implementing treatments for ADHD among girls. Major findings illustrate that neural pruning, testosterone (in conjunction with monoamine oxidase [MAOA] gene expression), and the sex-determining region Y gene (SRY) contribute to differences in hypofunctioning DA systems among males versus females. In addition, expression of the 5-HT transporter gene (5HTTLPR) and estrogen levels during premenstrual syndrome (PMS) can contribute to dysregulation of the 5-HT system, leading to sex differences in ADHD symptoms. These findings suggest that sex divergences in neurochemical system function underlie at least some differences in ADHD expression.

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ADHD, sex differences, neurochemical systems, dopamine, serotonin

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