Sex differences in Attention Deficit Hyperactivity Disorder: Candidate genetic and endocrine mechanisms

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is a developmental condition characterised by severe inattention, pathological impulsivity and hyperactivity; it is relatively common affecting up to 6% of children, and is associated with a risk of long-term adverse educational and social consequences. Males are considerably more likely to be diagnosed with ADHD than females; the course of the disorder and its associated co-morbidities also appear to be sensitive to sex. Here, I discuss fundamental biological (genetic and endocrine) mechanisms that have been shown to, or could theoretically, contribute towards these sexually dimorphic phenomena. Greater understanding of how and why the sexes differ with respect to ADHD vulnerability should allow us to identify and characterise novel protective and risk factors for the disorder, and should ultimately facilitate improved diagnosis, prognosis and treatment.

Genetic dissection of neural circuits underlying sexually dimorphic social behaviours

“…Furthermore, many neuro-psychiatric disorders exhibit sex differences in incidence, prevalence or disease outcome [161][162][163][164][165]. The reasons underlying these sex differences are poorly understood.…”

Biological factors underlying sex differences in neurological disorders

“…Symptomatically, males with ADHD appear more hyperactive whereas female ADHD patients are more inattentive (Davies, 2014;Lahey et al, 1994). These differences are also reflected in animal models of ADHD, such as the spontaneously hypertensive rat (SHR) model (Berger and Sagvolden, 1998).…”

“…These differences are also reflected in animal models of ADHD, such as the spontaneously hypertensive rat (SHR) model (Berger and Sagvolden, 1998). Most genome-wide association studies (GWAS) in ADHD patients have yet to successfully establish any common polymorphisms (besides copy number variants) that might be a risk factor for ADHD and/or male ADHD (Davies, 2014;Stergiakouli et al, 2012;Williams et al, 2012;Yang et al, 2013). However, GWAS and family-based association studies have reported an association between ADHD and catecholamine machinery genes such as DBH, DRD2, DDC, COMT and DRD4 (Lasky- Su et al, 2007Su et al, , 2008a.…”

How does sex matter? Behavior, stress and animal models of neurobehavioral disorders

“…2003; Fombonne, 2009;Werling and Geschwind, 2013;Davies, 2014;Schaafsma and Pfaff, 2014). Major depression, which is the most prevalent mental disorder worldwide according the World Health Organization statistics (WHO, 2015), is twice more common in women than in men and such sex differences extend to the presentation, the course of the illness and the treatment efficacy (Ahnlund and Frodi, 1996;Kessler et al, 1993;Kornstein, 1997;Angst et al, 2002;Gorman, 2006;Kessler, 2007;Wittchen et al, 2011).…”