Abstract
ObjectiveAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Relevant sex differences in symptomatology are discussed. This study compared brain neurometabolism in the anterior cingulate cortex (ACC) and left cerebellar hemisphere in age- and IQ-matched adult male (mADHD) and female (fADHD) ADHD patients.MethodsWe studied 48 (ACC) and 42 (cerebellum) male/female pairs of stimulant-free patients with adult ADHD. Single voxel magnetic resonance spectroscopy (MRS) was used to investigate creatine (Cre), total choline (t-Cho), glutamate + glutamine (Glx), N-acetylaspartate, and myo-inositol. The mADHD and fADHD groups were compared using robust linear regression. The level of significance was corrected for multiple tests using the Benjamini-Hochberg approach.ResultsFor the ACC, the signals of Cre (p = 0.008) and t-Cho (p = 0.004) showed significant effects of the age covariate as well as an interaction of sex and age (Cre: p = 0.033; t-Cho: p = 0.040). For the Glx signal, an interaction of sex and age could also be observed (p = 0.033). For cerebellar neurometabolites, the signals of t-Cho (p = 0.049) and Glx (p = 0.049) showed significant effects of the factor sex.ConclusionThis is the largest study yet to analyze sex differences in brain neurochemistry in adult patients with ADHD. Different age-dependent t-Cho signals in the ACC might be associated with delayed myelinization in mADHD. Further MRS studies in adult ADHD, accounting for possible sex effects, are warranted to validate the present findings.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder, with prevalence rates of 3–5% in childhood [19, 31]
In a previous meta-analysis by our group, we found an increase in the total choline (t-Cho) signal in the striatum and right frontal lobe of children with ADHD and in the bilateral pregenual anterior cingulate cortex (ACC) of adults with ADHD [38]
The psychometric scores for ADHD symptoms did not differ significantly between the male ADHD (mADHD) and female ADHD (fADHD) groups
Summary
Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder, with prevalence rates of 3–5% in childhood [19, 31]. The prevalence rates in adulthood are estimated to be 1.4– 3.6% [18]. The core symptoms of ADHD are inattention and hyperactivity combined with impulsivity, emotional instability, disorganized behavior, impaired affect control, and emotional hyper-reactivity [14, 19, 31, 42]. The pathophysiology of ADHD The dopaminergic and noradrenergic systems seem to play a central role in the pathophysiology of ADHD [6, 42]. The hypothesis that a dopaminergic (and noradrenergic) deficit plays a role in ADHD is supported by the effectiveness of methylphenidate in treating the condition [58]. Dopamine closely interacts with the glutamate system.
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