Spring 2008 Colloquia

Abstract

     Scientists have relied on cognitive paradigms in initial efforts to map the effects of genes on the brain in mental illness.  The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene encodes an enzyme involved in the inactivation of catecholamines (dopamine, adrenaline, and noradrenaline) and resides in chromosomal region 22q11.  Evidence suggests an association between the val allele (i.e., less catecholamine activity) and the diagnosis of schizophrenia, decreased performance on cognitive tasks, and decreased efficiency of prefrontal cortex.  

     Nonetheless, in studies of schizophrenia the met allele has been related to impaired shifting of a response rule based on feedback, reduced ability to sustain smooth pursuit eye movements in the brief absence of a target, greater vulnerability to visual backward masking effects, and increased low frequency electroencephalography activity over frontal brain regions during resting state.  The COMT region of the genome has also been associated with bipolar disorder with some studies pointing to the met allele being tied to bipolar disorder.

      Thus, it appears that the Val158Met polymorphism may exert varying effects on different forms of psychopathology depending on the allele and the mental disorder.  Application of cognitive paradigms to individuals with or at genetic risk for schizophrenia suggests that the COMT gene is salient to select aspects of brain pathology that may give rise to schizophrenia.

Suggested reading:

• Noah C. Venables, Edward M. Bernat, and Scott R. Sponheim, (2008) Genetic and Disorder-Specific Aspects of Resting State EEG Abnormalities in Schizophrenia, Schizophrenia Bulletin (advance access)
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