Cardiovascular risk and incidence of depression in young and older adults: evidence from the SUN cohort study

ANCOVA analysis, which included age and education as covariates. The model also remained significant in a follow-up analysis in which participants who identified as AfricanAmerican (N515) were excluded. Carriers of the 5HTTLPR-S’ allele had increased PTSD symptoms compared to individuals homozygous for the L’ allele (IES mean score: L’L’547.3 6 5.3, S559.8 6 4.1). For DISC1, individuals homozygous for the T allele had increased PTSD symptoms compared to A carriers (A545.3 6 2.8, TT561.9 6 7.2). In ANCOVA analysis of symptom sub-factors, 5-HTTLPR and DISC1 selectively influenced intrusion and hypervigilance symptoms, but did not affect avoidance symptoms. PTSD symptom severity (total IES scores) increased by an average of 40% with each risk genotype (none538.4, one5 54.5, two565.6). These data support prior observations of 5-HTTLPR effects on PTSD symptoms in military veterans. Although 5-HTTLPR has been identified as a potential contributor to PTSD susceptibility in civilian-based populations, its effect may be less robust in those populations, due to lower overall level of trauma exposure. The effects of 5-HTTLPR on PTSD in military veterans after deployment to a war zone may be more robust because of a universal and constant exposure to threat, military training, and/or separation from family and home social support. In addition to 5-HTTLPR, genetic variation in DISC1, a gene associated with susceptibility to multiple mental disorders, was found to contribute to PTSD symptom severity. Possessing both DISC1 and 5-HTTLPR risk genotypes resulted in a 1.7fold increase in PTSD symptoms. Although this is the first report of DISC1 S704C TT allele as a risk factor for PTSD, the finding is not surprising, considering that this allele has been identified as a risk factor for major depression. DISC1 variants interfere with a protein complex important for organelle transport and in tethering of mitochondria, interfering with dendritic development and reducing densities of dendritic spines in the frontal cortex, paralleling our recent report of spine density reductions in the frontal cortex in PTSD. This study was powered to screen for candidate genes with relatively large effect sizes on PTSD symptoms in combat veterans, which may be different from sets of genes affecting PTSD in civilian populations. Study of the serotonin system in PTSD is motivated in large part by the therapeutic utility of serotonin uptake inhibitors to treat symptoms of PTSD. Our data provide additional impetus for continued study of this system in PTSD pharmacotherapy. In addition, antipsychotics such as risperidone have been shown to reverse DISC1-related behavioral deficits and pathophysiology in animal models, suggesting the possibility that such agents could be re-examined for use as alternative pharmacotherapies for PTSD. Keith A. Young, Sandra B. Morissette, Robert Jamroz, Eric C. Meyer, Matthew S. Stanford, Li Wan, Nathan A. Kimbrel Central Texas Veterans Health Care System, Temple, TX, USA; Department of Veterans Affairs VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA; Department of Psychiatry and Behavioral Science, Texas A&M Health Science Center, Temple, TX, USA; University of Texas at San Antonio, San Antonio, TX, USA; Hope and Healing Center & Institute, Houston, TX, USA; Durham Veterans Affairs Medical Center, Durham, NC, USA; VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC, USA; Duke University Medical Center, Durham, NC, USA