Endothelial function, folate pharmacogenomics, and neurocognition in psychotic disorders.
Cardiovascular disease (CVD) is a well-described complication of schizophrenia, however, mechanisms connecting CVD with other facets of psychotic disorders, such as neurocognition, are not understood. The current study examined folate metabolism as a potential mechanism of CVD and neurocognitive deficits by: 1) using endothelial dysfunction as a biomarker of CVD, and 2) comparing enzymes associated with neurocognition, CVD, and critical to folate metabolism, methylenetetrahydrofolate reductase (MTHFR) and catechol-o-methyl transferase (COMT). Endothelial function was assessed in 147 participants with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified grouped by MTHFR and COMT allele status. Regression models were used to compare neurocognitive performance based on the Brief Assessment of Cognition in Schizophrenia (BACS). Overall, endothelial function predicted BACS composite z-scores after controlling for age, race, level of education, serum folate levels, and MTHFR/COMT risk allele status. Participants with at least one or more MTHFR and/or COMT risk alleles had lower BACS Composite and BACS Symbol Coding adjusted mean z-scores than those with both MTHFR CC and COMT Met/Met genotypes. Thus, endothelial dysfunction may contribute to the neurocognitive deficits seen in psychotic disorders. CVD interventions may not only reduce CVD-related morbidity, but also lessen progressive neurocognitive deficits reported in psychotic disorders.
Department of Psychology, University of Michigan, 530 Church Street, Ann Arbor, MI 48109, USA.
Tyler
T
Grove
Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI 48109, USA.
Stephan
S
Taylor
Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI 48109, USA.
Gregory
G
Dalack
Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI 48109, USA; College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA. Electronic address: vellingr@med.umich.edu.
Vicki
V
Ellingrod
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009483:Neuropsychological Tests; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D055815:Young Adult
D014150:Antipsychotic Agents; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002394:Catechol O-Methyltransferase
Cardiovascular disease; Endothelial function; Folate; Neurocognition; Pharmacogenomics; Schizophrenia