title: Dietary, lifestyle and pharmacogenetic factors associated with arteriole endothelial-dependent vasodilatation in schizophrenia patients treated with atypical antipsychotics (AAPs).
abstract: OBJECTIVE
  Within schizophrenia cardiovascular disease (CVD) is highly prevalent secondary to atypical antipsychotic (AAP) use. Thorough assessments of diet, lifestyle, and endothelial functioning have not been done in this population. Omega 3 Fatty Acids (N-3 FAs) have garnered attention in relation to psychopathology as well as cardioprotection. This study examined the status of endothelial function within the schizophrenia population and determined pharmacogenetic, medication, dietary, and lifestyle factors associated with this functioning.
  
  
  METHODS
  Schizophrenia subjects were screened for the metabolic syndrome along with physical activity, smoking, and variants related to folate pharmacogenetics in this cross-sectional analysis. Arteriole endothelial-dependent vasodilatation was measured using non-invasive peripheral arterial tonometry (RH-PAT, EndoPAT2000). A 24h dietary food recall was used to construct intake profiles using the Nutrition Data Systems for Research software (NDSR). We examined associations between AAP use and RH-PAT values, and the influence of N-3 FA dietary intake on this measure. Preliminary data are reported in 83 subjects with a mean age (±s.d.) of 45.89 (±11.49), 64% were Caucasian (n=53), 64% were male (n=53), and 77% were receiving AAP treatment (n=63).
  
  
  RESULTS
  A significant positive relationship was found between RH-PAT values and N-3 FA intake (F=17.7(1,16), p=0.0007) in subjects not receiving AAPs. This relationship was lost in those treated with AAPs (F=0.25(1,43), p>0.6). Regression analysis confirmed the interaction effect of AAP treatment on the relationship between RH-PAT and N-3 FAs (p=0.0105). Endothelial dysfunction was also related to folate pharmacogenetic variants.
  
  
  CONCLUSIONS
  AAPs may counteract some vascular health benefits of a diet high in N-3 FAs. AAP use may necessitate a higher N-3 FA dose to regain these effects, but additional research is necessary to strengthen the preliminary findings. Pharmacogenetic variants related to folate and homocysteine metabolism may also increase endothelial dysfunction risk.
authors.affiliation: University of Michigan, College of Pharmacy, Department of Clinical Social and Administrative Sciences, 428 Church Street, Ann Arbor, Michigan 48109, USA. vellingr@umich.edu
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
authors.forename: Stephan F
authors.initials: SF
authors.lastname: Taylor
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Evans
authors.forename: Sebastian K
authors.initials: SK
authors.lastname: Zöllner
authors.forename: Tyler B
authors.initials: TB
authors.lastname: Grove
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Gardner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bly
authors.forename: Rodica
authors.initials: R
authors.lastname: Pop-Busui
authors.forename: Gregory
authors.initials: G
authors.lastname: Dalack
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003430:Cross-Sectional Studies; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008019:Life Style; D008297:Male; D008365:Manometry / Q000379:methods; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012044:Regression Analysis; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D045462:Endothelium-Dependent Relaxing Factors; D015525:Fatty Acids, Omega-3; D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002394:Catechol O-Methyltransferase