COMT, neuropsychological function and brain structure in schizophrenia: A systematic review and neurobiological interpretation

TY - JOUR

T1 - COMT, neuropsychological function and brain structure in schizophrenia

T2 - A systematic review and neurobiological interpretation

AU - Ira, Elisa

AU - Zanoni, Martina

AU - Ruggeri, Mirella

AU - Dazzan, Paola

AU - Tosato, Sarah

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate the link between neuropsychological impairments and brain structural abnormalities associated with the COMT Val158Met polymorphism in patients with schizophrenia to improve understanding of the pathophysiology of this disorder. Methods: We performed a systematic review using studies identified in PubMed and MEDLINE (from the date of the first available article to July 2012). Our review examined evidence of an association between the COMT Val158Met polymorphism and both neuro psychological performance and brain structure in patients with psychosis, in their relatives and in healthy individuals (step 1). The review also explored whether the neuropsychological tasks and brain structures identified in step 1 met the criteria for an endophenotype (step 2). Then we evaluated evidence that the neuropsychological endophenotypes identified in step 2 are associated with the brain structure endophenotypes identified in that step (step 3). Finally, we propose a neurobiological interpretation for this evidence. Results: A poorer performance on the n-back task and the Continuous Performance Test (CPT) and smaller temporal and frontal brain areas were associated with the COMT Val allele in patients with schizophrenia and their relatives and met most of the criteria for an endo - pheno type. It is possible that the COMT Val158Met polymorphism therefore contributes to the development of these neuropsychological and brain structural endophenotypes of schizophrenia, in which the prefrontal cortex may represent the neural substrate underlying both n-back and CPT performances. Limitations: The association between a single genetic variant and an endophenotype does not necessarily imply a causal relationship between them. Conclusion: This evidence and the proposed interpretation contribute to explain, at least in part, the biological substrate of 4 important endophenotypes that characterize schizophrenia.

AB - Background: Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate the link between neuropsychological impairments and brain structural abnormalities associated with the COMT Val158Met polymorphism in patients with schizophrenia to improve understanding of the pathophysiology of this disorder. Methods: We performed a systematic review using studies identified in PubMed and MEDLINE (from the date of the first available article to July 2012). Our review examined evidence of an association between the COMT Val158Met polymorphism and both neuro psychological performance and brain structure in patients with psychosis, in their relatives and in healthy individuals (step 1). The review also explored whether the neuropsychological tasks and brain structures identified in step 1 met the criteria for an endophenotype (step 2). Then we evaluated evidence that the neuropsychological endophenotypes identified in step 2 are associated with the brain structure endophenotypes identified in that step (step 3). Finally, we propose a neurobiological interpretation for this evidence. Results: A poorer performance on the n-back task and the Continuous Performance Test (CPT) and smaller temporal and frontal brain areas were associated with the COMT Val allele in patients with schizophrenia and their relatives and met most of the criteria for an endo - pheno type. It is possible that the COMT Val158Met polymorphism therefore contributes to the development of these neuropsychological and brain structural endophenotypes of schizophrenia, in which the prefrontal cortex may represent the neural substrate underlying both n-back and CPT performances. Limitations: The association between a single genetic variant and an endophenotype does not necessarily imply a causal relationship between them. Conclusion: This evidence and the proposed interpretation contribute to explain, at least in part, the biological substrate of 4 important endophenotypes that characterize schizophrenia.

UR - http://www.scopus.com/inward/record.url?scp=84886671321&partnerID=8YFLogxK

U2 - 10.1503/jpn.120178

DO - 10.1503/jpn.120178

M3 - Review article

C2 - 23527885

AN - SCOPUS:84886671321

SN - 1180-4882

VL - 38

SP - 366

EP - 380

JO - Journal of Psychiatry and Neuroscience

JF - Journal of Psychiatry and Neuroscience

IS - 6

ER -