Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a...

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition associated with cognitive dysfunction. The Cambridge Neuropsychological Test Automated Battery is a computerized set of tests that has been widely used in ADHD and in translation/back-translation. Following a survey of translational research relevant to ADHD in experimental animals, a comprehensive literature review was conducted of studies that had used core Cambridge Neuropsychological Test Automated Battery tests 1) to evaluate cognitive dysfunction in ADHD and 2) to evaluate effects of salient drugs in patients and in volunteers. Meta-analysis was conducted where four or more independent datasets were available. Meta-analysis revealed medium-large decrements in ADHD for response inhibition (d = .790, p < .001), working memory (d = .883, p < .001), executive planning (d = .491, p < .001), and a small decrement in attentional set shifting (d = .160, p = .040). Qualitative review of the literature showed some consistent patterns. In ADHD, methylphenidate improved working memory, modafinil improved planning, and methylphenidate, modafinil, and atomoxetine improved inhibition. Meta-analysis of modafinil healthy volunteer studies showed no effects on sustained attention or set shifting. Results were paralleled by findings in experimental animals on comparable tests, enabling further analysis of drug mechanisms. Substantial cognitive deficits are present in ADHD, which can be remediated somewhat with current medications and which can readily be modeled in experimental animals using back-translational methodology. The findings suggest overlapping but also distinct early cognitive effects of ADHD medications and have important implications for understanding the pathophysiology of ADHD and for future trials.