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

Liang-Jen Wang,1,2 Miao-Chun Chou,1 Wen-Jiun Chou,1 Min-Jing Lee,1 Sheng-Yu Lee,3,4 Pao-Yen Lin,5 Yi-Hsuan Lee,1 Yi-Hsin Yang,6 Cheng-Fang Yen2,7 1Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 2Department of Psychiatry, School of Medicine, and Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 3Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, 4Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, 5Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 6School of Pharmacy, Kaohsiung Medical University Hospital, 7Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Objective: Both 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).Methods: Two 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).Results: Lower 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