Effect of COMT Val158Met genotype on attention and response to methylphenidate following traumatic brain injury.
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 × genotype interaction: (F(2,29) = 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.
School of Psychology & Psychiatry, Monash University , Australia .
Catherine
C
Willmott
Jennie
J
Ponsford
Thomas W
TW
McAllister
Richard
R
Burke
D000328:Adult; D000483:Alleles; D001288:Attention / Q000187:drug effects*; D001315:Australia / Q000453:epidemiology; D001930:Brain Injuries / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D018592:Cross-Over Studies; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine; D008774:Methylphenidate / Q000494:pharmacology* / Q000627:therapeutic use; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D011597:Psychomotor Performance; D013647:Task Performance and Analysis; D016896:Treatment Outcome; D014633:Valine
D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D008715:Methionine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D014633:Valine