Effect of COMT Val158Met genotype on attention and response to methylphenidate following traumatic brain injury

Primary objective: To investigate whether COMT Val158Met allele status was associated with (i) attentional performance and (ii) response to methylphenidate (MP) following traumatic brain injury (TBI). Methods: Forty healthy controls and 32 patients with moderate-severe TBI (Mean time post-injury = 68 days) completed a baseline cognitive assessment. The TBI cohort then participated in a randomized, cross-over, double blind, placebo controlled 2-week MP trial. MP was administered at 0.3 mg/kg twice daily. TBI genotype distribution: val/val n = 11; val/met n = 14; met/met n = 7. Results: There were no significant differences across genotypes on baseline attentional measures. When compared with controls, the val/val group performed significantly more poorly on most measures. The met/met group performed more poorly than controls on measures of speed, but not in strategic control of attention. MP resulted in faster speed of information processing. Repeated measures mixed ANOVAs found only one significant drug x genotype interaction: (F-(2,F-29) = 4.257, p = 0.024) the met/met group demonstrated a greater response to MP on the Symbol Digit Modalities Test. Conclusions: COMT allele status was not strongly associated with attentional performance or response to MP in the TBI sample. The met/met group, whilst performing slowly, had relatively preserved strategic control of attention.