Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

Diabetes and Cardiovascular Care Among People with Severe Mental Illness: A Literature Review

Close to 19 million US adults have severe mental illnesses (SMI), and they die, on average, 25 years earlier than the general population, most often from cardiovascular disease (CVD). Many of the antipsychotic medications used to treat SMI contribute to CVD risk by increasing risk for obesity, type 2 diabetes, dyslipidemia, and hypertension. Based on compelling evidence, the American Diabetes Association and the American Psychiatric Association developed guidelines for metabolic screening and monitoring during use of these medications. In this manuscript, we have reviewed the evidence on diabetes and other CVD risk screening, prevalence, and management among populations with SMI. We also review differences in screening among subpopulations with SMI (e.g., racial/ethnic minorities, women, and children). We found that despite national guidelines for screening for diabetes and other cardiovascular risk factors, up to 70 % of people taking antipsychotics remain unscreened and untreated. Based on estimates that 20 % of the 19 million US adults with SMI have diabetes and 70 % of them are not screened; it is likely that over 2 million Americans with SMI have unidentified diabetes. Given that undiagnosed diabetes costs over $4,000 per person, this failure to identify diabetes among people with SMI represents a missed opportunity to prevent morbidity and translates to over$8 billion in annual preventable costs to our healthcare system. Given the high burden of disease and significant evidence of suboptimal medical care received by people with SMI, we propose several clinical and policy recommendations to improve diabetes and other CVD risk screening and care for this highly vulnerable population. These recommendations include reducing antipsychotic medication dose or switching antipsychotic medications, enhancing smoking cessation efforts, sharing electronic health records between physical and mental health care systems, and promoting integration of care

Lack of association between DRD2 and OPRM1 genotypes and adiposity

BACKGROUND: Dopaminergic and opioid systems are both involved in food intake and appetite control. The dopamine D2 receptor gene (DRD2) and the μ-opioid receptor gene (OPRM1) therefore represent plausible candidates for association with obesity. OBJECTIVE: Previous studies of these variants have yielded inconsistent findings, which are likely due to insufficient statistical power. The aim of the current study was to determine whether, in a large population-based sample, there are associations between adiposity and (i) the A1 (T) allele of the Taq1A polymorphism (rs1800497) in DRD2 and (ii) the G allele of the A118G polymorphism (rs1799971) in OPRM1. STUDY POPULATION: Annual clinic-based measures of body mass index (BMI) and waist circumference were taken from children (N=3720) at 5 measurement time points from ages 7 through to 11 years. BMI was also recorded in their mothers (N=2460) at comparable time points and at pre-pregnancy. All participants were genotyped. Our study was powered (at 80%) to detect per-allele effects on BMI of 0.21 kg m(−2). RESULTS: Our results indicate a lack of association between DRD2 and OPRM1 genotypes and adiposity. Combining the data across mothers and children found per-allele effects on BMI of 0.02 kg m(−2) (95% confidence interval (CI): −0.17, 0.20), P=0.9 for rs1800497 and −0.08 kg m(−2) (95% CI: −0.29, 0.22), P=0.4 for rs1799971. As a positive control, we also examined the effect of FTO genotype over the same time period and confirmed the expected relationship between variability at this locus and higher adiposity. CONCLUSION: Our findings question existing evidence suggesting associations at DRD2 and OPRM1 loci and adiposity. They also highlight the caution required when employing candidate gene approaches to further our understanding of the neurobiology of eating and obesity