Potential role of pre- and postnatal testosterone levels in attention-deficit/hyperactivity disorder: is there a sex difference?

Abstract

ObjectiveBoth prenatal testosterone (T) exposure and postnatal T levels have been associated with developing neural circuitry and behavioral systems. This study examined the potential correlation between pre- and postnatal T levels and behavioral and neurocognitive profiles of children with attention-deficit/hyperactivity disorder (ADHD).MethodsTwo hundred ADHD patients with a mean age of 8.7±2.0 years (158 boys and 42 girls) were recruited. The ratio of the length of the right index finger (2D) to that of the right ring finger (4D) (2D/4D ratio) served as a surrogate of prenatal T exposure, and postnatal T was determined using salivary T concentration. Behavioral symptoms were evaluated using the Swanson, Nolan, and Pelham – Version IV Scale for ADHD (SNAP-IV). Neurocognitive function was assessed using the Wechsler Intelligence Scale for Children – Fourth Edition (WISC-IV) and Conners’ Continuous Performance Test (CPT).ResultsLower 2D/4D ratios were associated with comorbid disruptive behavior disorders (t=2.15, P=0.033) in all participants. Among the boys with ADHD, neither 2D/4D ratios nor salivary T levels were associated with behavioral symptoms or neurocognitive function. Among the girls with ADHD, the salivary T level was positively correlated with the Perceptual Reasoning Index of the WISC-IV (r=0.48, P=0.001) and the Confidence Index (r=0.37, P=0.017) and Omission Errors of the CPT (r=0.62, P<0.001).ConclusionFindings suggest that a higher prenatal T exposure is associated with a greater risk of developing disruptive behavior disorders, and T may exert differential neurocognitive effects between boys and girls with ADHD. However, the neurobiological mechanisms of T involved in the pathogenesis of ADHD warrant further investigation.

The Relationship between Second-to-Fourth Digit Ratios, Attention-Deficit/Hyperactivity Disorder Symptoms, Aggression, and Intelligence Levels in Boys with Attention-Deficit/Hyperactivity Disorder

“…Several studies have investigated the correlation between 2D:4D ratios and ADHD symptom severity. 11,13,15,19,21 Similar to the results of our study, some studies showed a correlation between the 2D:4D ratios and hyperactive/impulsive symptoms. Williams et al, 19 explored right-hand 2D:4D ratios associations with childhood problem behaviors and showed that lower 2D:4D ratios were associated with increased hyperactivity levels in girls, but not boys.…”

“…To our knowledge, there is only one study examining the relationship between intelligence and 2D:4D ratios in patients with ADHD. 11 In this study, Wang et al, 11 demonstrated no statistically significant correlations between 2D: 4D ratios and WISC-IV Chinese version. In our study, no correlation was found between WISC-R intelligence test verbal, performance, and total score, and subtest scores and the ratios of 2D:4D in ADHD.…”

“…15 Lemiere et al, 15 showed that the ratios of 2D:4D were statistically unrelated to any of the behavior assessment scales in the total group or the ADHD group. In recent study conduct by Wang et al, 11 also showed that the ratios of 2D:4D were not correlated with behavioral symptoms among the boys with ADHD. In our study, only the left-hand ratios of 2D:4D were found to be correlated with the hyperactivity subscales of the teacher-rated scales.…”

“…However, only a small number of studies investigate the relation between the ratios of 2D:4D and intelligence. 11,46 Because of the complex nature of the observed association between 2D:4D ratios and intelligence, Luxen and Buunk 46 found evidence of an association between the ratios of 2D:4D and intelligence and detected a positive correlation between verbal intelligence and righthand 2D:4D ratios, a negative correlation between numerical intelligence and right-hand 2D:4D ratios. Brosnan 47 demonstrated that 2D:4D ratios were positively correlated with literacy for females and negatively correlated with numeracy for males at age seven.…”

“…Also, to date, there is only one study examining the relation between the 2D: 4D ratios and intelligence quotient (IQ) in the ADHD sample. 11 However, investigation of this relationship is worthwhile, as a recent review has stated that giftedness is related to higher levels of prenatal testosterone exposure. 24 In the current study, we measured the ratios of 2D:4D and administered a Wechsler Intelligence Scale for Children-Revised (WISC-R) to assess IQ scores, as well as behavioral rat-ing scales, in children with ADHD and comparison individuals.…”