Vasculopathy Related to Manic/Hypomanic Symptom Burden and First-Generation Antipsychotics in a Sub-Sample from the Collaborative Depression Study
Psychotherapy and Psychosomatics, Exclusive Author Commentary  Clinical Article

Fiedorowicz JG et al. – The 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.

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.

In a prior analysis of 435 individuals with bipolar disorder from the Collaborative Depression Study (CDS), we found manic/hypomanic symptom burden (chronicity of clinically significant manic/hypomanic symptomatology) was significantly associated with cardiovascular mortality (Fiedorowicz et al. Psychosom Med 2009). This appeared to account for the greater risk of cardiovascular mortality in bipolar I, relative to bipolar II disorder as observed in the CDS sample and the only prior study to assess mortality differences by bipolar subtype (Angst F et al. J Affect Disord 1994). We were interested in replicating and extending the prior finding. To do so, we recruited a small subset of participants from the CDS, whose course of illness had been prospectively assessed for over a quarter century through participation, for a quantitative metabolic and vascular phenotyping assessment. We analogously found a dose-response relationship between manic/hypomanic symptom burden and endothelial dysfunction, based on a relationship with poorer flow-mediated but not nitroglycerin-mediated vasodilation. While difficult to study as reliable data is seldom available, the assessment of a dose-response between the long-term chronicity of illness and vascular outcomes circumvents some of the issues related to selection bias in case control studies (e.g. inpatient registry compared to national data) and provides additional evidence for a causal relationship between bipolar disorder and vascular disease. Such methods may assist in the identification of the most relevant mechanisms mediating the well-established relationship between bipolar disorder and vascular mortality (reviewed by Murray et al. Curr Psychiatry Rep 2009; Weiner M et al. Ann Clin Psychiatry 2011). References: Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord 2002;68:167-81. Fiedorowicz JG, Coryell WH, Rice JP, Warren LL, Haynes WG. Vasculopathy Related to Manic/Hypomanic Symptom Burden and First-Generation Antipsychotics in a Sub-Sample from the Collaborative Depression Study. Psychotherapy and Psychosomatics 2012;81:235-43. Fiedorowicz JG, Solomon DA, Endicott J, Leon AC, Li C, Rice JP, et al. Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder. Psychosom Med 2009;71:598-606. Murray DP, Weiner M, Prabhakar M, Fiedorowicz JG. Mania and mortality: why the excess cardiovascular risk in bipolar disorder? Curr Psychiatry Rep 2009;11:475-80. Weiner M, Warren L, Fiedorowicz JG. Cardiovascular morbidity and mortality in bipolar disorder. Ann Clin Psychiatry 2011;23:40-7.

Please login or register to follow this author.
► Click here to access PubMed, Publisher and related articles...
<< Previous Article | Next Article >>

Your Unread Messages in Psychiatry

See All >> Messages include industry-sponsored communications and special communications from MDLinx

Most Popular Psychiatry Articles

1 Zolpidem and the risk of Parkinson's disease: A nationwide population-based study Journal of Psychiatric Research, August 1, 2014    Clinical Article

2 Blood manganese levels in relation to comorbid behavioral and emotional problems in children with attention-deficit/hyperactivity disorder Psychiatry Research, November 4, 2014    Clinical Article

3 Maternal age at childbirth and risk for ADHD in offspring: a population-based cohort study International Journal of Epidemiology, November 18, 2014    Clinical Article

4 The influence of inflammatory cytokines in physiopathology of suicidal behavior Journal of Affective Disorders, November 5, 2014    Evidence Based Medicine    Review Article

5 Maternal use of selective serotonin reuptake inhibitors and risk of miscarriage - assessing potential biases Paediatric and Perinatal Epidemiology, November 12, 2014    Clinical Article

6 Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: A systematic review and meta-analysis of randomized clinical trials JAMA Psychiatry, October 22, 2014    Evidence Based Medicine    Clinical Article

7 Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis Journal of Child Psychology and Psychiatry, November 19, 2014    Evidence Based Medicine

8 Investigation of the Montreal Cognitive Assessment (MoCA) as a cognitive screener in severe mental illness Psychiatry Research, November 10, 2014    Clinical Article

9 Is depression associated with increased oxidative stress?: A systematic review and meta-analysis Psychoneuroendocrinology, November 7, 2014    Evidence Based Medicine

10 Obesity and major depression: Body-mass index (BMI) is associated with a severe course of disease and specific neurostructural alterations Psychoneuroendocrinology, November 6, 2014    Clinical Article

11 Serum dehydroepiandrosterone sulfate and incident depression in the elderly: The Pro.V.A Study The American Journal of Geriatric Psychiatry, November 24, 2014    Clinical Article

12 Effects of perinatal mental disorders on the fetus and child The Lancet, November 21, 2014    Evidence Based Medicine    Clinical Article

13 Antidepressant–induced sexual dysfunction during treatment with fluoxetine, sertraline, and trazodone: A randomized controlled trial General Hospital Psychiatry, November 7, 2014    Clinical Article

14 The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders Full Text Translational Psychiatry, November 26, 2014    Free full text    Clinical Article

15 Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period The Lancet, November 20, 2014    Evidence Based Medicine

16 Comparative efficacy and acceptability of drug treatments for bipolar depression: A multiple-treatments meta-analysis Acta Psychiatrica Scandinavica, October 10, 2014    Evidence Based Medicine    Clinical Article

17 Behavioral activation therapy for return to work in medication-responsive chronic depression with persistent psychosocial dysfunction Comprehensive Psychiatry, November 13, 2014    Clinical Article

18 Specific and common genes implicated across major mental disorders: A review of meta-analysis studies Journal of Psychiatric Research, November 17, 2014    Review Article

19 Association between toll-like receptors expression and major depressive disorder Psychiatry Research, November 11, 2014    Clinical Article

20 The effect of bupropion XL and escitalopram on memory and functional outcomes in adults with major depressive disorder: Results from a randomized controlled trial Psychiatry Research, November 4, 2014    Clinical Article

Indexed Journals in Psychiatry : Current Psychiatry, Bipolar Disorders, American Journal of Psychiatry, Addictionmore