BACKGROUND: Fundamental cause theory posits that social conditions strongly influence the risk of health risks. This study identifies risk mechanisms that social conditions associated with socioeconomic status (SES) and race/ethnicity shape in the production of colorectal cancer (CRC) mortality. METHODS: Two large datasets in the United States examining behavioral and medical preventive factors (N = 4.63-million people) were merged with population-level mortality data observing 761,100 CRC deaths among 3.31-billion person-years of observation to examine trends in CRC mortality from 1999-2012. Analyses examined the changing role of medical preventions and health behaviors in catalyzing SES and racial/ethnic inequalities in CRC mortality. RESULTS: Lower SES as well as Black, Hispanic, Asian/Pacific Islander, and Native American race/ethnicity were associated with decreased access to age-appropriate screening and/or increased prevalence of behavioral risk factors. Analyses further revealed that SES and racial/ethnic inequalities were partially determined by differences in engagement in two preventive factors: use of colonoscopy, and participation in physical activity. DISCUSSION: Social inequalities were not completely determined by behavioral risk factors. Nevertheless, a more equitable distribution of preventive medicines has the potential to reduce both the risk of, and social inequalities in, CRC mortality.

Inflammation is known to be associated with posttraumatic stress disorder (PTSD). It is not known if total white blood cell (WBC) count, a routinely checked inflammatory marker, is associated with PTSD symptom trajectories using medical record data. We used latent class growth analysis to identify three-year PTSD symptom trajectories using PTSD Checklist (PCL) scores. The outcome for each patient was maximum WBC count from index PTSD diagnosis to last PCL. Using linear regression analysis, we then calculated and compared the average WBC count for each trajectory before and after controlling for age, gender, race, obesity, smoking, diabetes, hypertension, cardiovascular disease, depression and other co-morbid inflammatory conditions. Patients were 40.2 (SD±13.5) years of age, 83.7% male and 67.9% white. We identified three PCL trajectory groups based on symptom severity over time: 'moderate-large decrease', 'moderate severe-slight decrease', and 'severe-persistent'. In adjusted analyses, 'severe-persistent' vs. 'moderate-large decrease' had significantly higher WBC count (B=0.64; 95%CI=0.18, 1.09; p=.006). Although non-significant, 'moderate severe-slight decrease' vs. 'moderate-large decrease' also had a higher WBC count (B=0.42; 95% CI: -0.02, 0.86; p=.061). Persistently severe PTSD is associated with a higher WBC count than improving PTSD. WBC appears to have utility for measuring the association between psychiatric disorders and inflammation in retrospective cohort studies involving large administrative medical record data bases.

Objective

High levels of psychological distress increase the risk of a wide range of medical diseases. In this study, we investigated the association between posttraumatic stress disorder (PTSD) and kidney disease.

Methods

World Trade Center (WTC) responders were included if they had two or more measures of estimated glomerular filtration rate (eGFR). The PTSD Checklist (PCL) was used to define no PTSD (PCL < 40), "mild" PTSD (40 ≤ PCL <50), and "severe" PTSD (PCL ≥50). Subtypes of PTSD by symptom clusters were analyzed. Multinomial logistic regression was used to estimate the association of PTSD with two GFR change outcomes (decline or increase) compared with the stable GFR outcome.

Results

In 2266 participants, the mean age was 53.1 years, 8.2% were female, and 89.1% were White. Individuals with PTSD (n = 373; 16.5%) did not differ in mean baseline GFR from individuals without PTSD (89.73 versus 90.56 mL min-1 1.73 m-2; p = .29). During a 2.01-year mean follow-up, a mean GFR decline of -1.51 mL min-1 1.73 m-2 per year was noted. In multivariable-adjusted models, PTSD was associated with GFR decline (adjusted relative risk [aRR] = 1.74 [1.32-2.30], p < .001) compared with stable GFR, with "hyperarousal" symptoms showing the strongest association (aRR =2.11 [1.40-3.19]; p < .001). Dose-response effects were evident when comparing mild with severe PTSD and comparing PTSD with versus without depression. PTSD was also associated with GFR rise (aRR = 1.47 [1.10-1.97], p < .009). The association between PTSD and GFR change was stronger in participants older than 50 years.

Conclusions

PTSD may be a novel risk factor for exaggerated longitudinal GFR change in young, healthy adults. These findings need to be validated in other cohorts.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.