title: Vasculopathy related to manic/hypomanic symptom burden and first-generation antipsychotics in a sub-sample from the collaborative depression study.
abstract: BACKGROUND
  Mood disorders substantially increase the risk of cardiovascular disease, though the mechanisms are unclear. We assessed for a dose-dependent relationship between course of illness or treatment with vasculopathy in a well-characterized cohort.
  
  
  METHODS
  Participants with mood disorders were recruited for the National Institute of Mental Health Collaborative Depression Study (CDS) and followed prospectively. A cross-sectional metabolic and vascular function evaluation was performed on a sub-sample near completion after a mean follow-up of 27 years.
  
  
  RESULTS
  A total of 35 participants from the University of Iowa (33) and Washington University (2) sites of the CDS consented to a metabolic and vascular function assessment at the Iowa site. In multivariate linear regression, controlling for age, gender, and smoking, manic/hypomanic, but not depressive, symptom burden was associated with lower flow-mediated dilation. Cumulative exposure to antipsychotics and mood stabilizers was associated with elevated augmentation pressure and mean aortic systolic blood pressure. This appeared specifically related to first-generation antipsychotic exposure and mediated by increases in brachial systolic pressure. Although second-generation antipsychotics were associated with dyslipidemia and insulin resistance, they were not associated with vasculopathy.
  
  
  CONCLUSIONS
  These results provide evidence that chronicity of mood symptoms contribute to vasculopathy in a dose-dependent fashion. Patients with more manic/hypomanic symptoms had poorer endothelial function. First-generation antipsychotic exposure was associated with arterial stiffness, evidenced by higher augmentation pressure, perhaps secondary to elevated blood pressure. Vascular phenotyping methods may provide a promising means of elucidating the mechanisms linking mood disorders to vascular disease.
authors.affiliation: Mathematics in Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. jess-fiedorowicz@uiowa.edu
authors.forename: Jess G
authors.initials: JG
authors.lastname: Fiedorowicz
authors.forename: William H
authors.initials: WH
authors.lastname: Coryell
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Lois L
authors.initials: LL
authors.lastname: Warren
authors.forename: William G
authors.initials: WG
authors.lastname: Haynes
mesh_terms: D000368:Aged; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000000981:diagnostic imaging; D003866:Depressive Disorder / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014463:Ultrasonography; D014652:Vascular Diseases / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology; D059289:Vascular Stiffness / Q000502:physiology
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents