Psychiatric disorders are characterized by breakdowns in higher brain functions (eg, memory, attention, emotion), which have a substantial genetic component. Elucidating the relationship between genetic variation and brain function variation is an important step in understanding the dispositions to psychiatric disorder. Some functional polymorphisms that have consequences for aspects of brain function will be described. These include the Val66Met substitution in brain-derived neurotrophic factor, the Val108/ 158Met substitution in catechol-O-methyl transferase, the ε2/3/4 polymorphism in apolipoprotein E, the serotonin transporter promoter deletion polymorphism and a variable number tandem repeat (VNTR) polymorphism that alters expression of monoamine oxidase A (MAOA).
We are investigating these variants using the Brain Resource International Database (BRID), a standardized and integrated database of brain function from healthy volunteers and targeted clinical groups. Data collected include neuropsychological and DASS-NEO test scores, cognition and emotion event-related potentials, autonomic measures, and structural and functional magnetic resonance imaging.
This approach is illustrated by our investigation of the MAOA VNTR polymorphism in 312 BRID participants. We detected subtle deficits in information processing and vigilance in people bearing the low-expressing genotype. Men with the ‘low’ genotype exhibited additional deficits in executive function.
Study of the genetic contributors to variation in normal brain function will provide insight into normal neurological processes and have direct relevance to our understanding of such disorders as depression, anxiety and Alzheimer's disease. Because the consequences of individual polymorphisms are generally subtle, an integrative approach that allows for large cohorts is essential to assess their effects.