USING MENDELIAN RANDOMISATION to INFER CAUSALITY in DEPRESSION and ANXIETY RESEARCH.

USING MENDELIAN RANDOMISATION TO INFER CAUSALITY IN DEPRESSION AND ANXIETY RESEARCH.

Depress Anxiety. 2013 Jul 11;
Gage SH, Smith GD, Zammit S, Hickman M, Munafò MR

Depression and anxiety co-occur with substance use and abuse at a high rate. Ascertaining whether substance use plays a causal role in depression and anxiety is difficult or impossible with conventional observational epidemiology. Mendelian randomisation uses genetic variants as a proxy for environmental exposures, such as substance use, which can address problems of reverse causation and residual confounding, providing stronger evidence about causality. Genetic variants can be used instead of directly measuring exposure levels, in order to gain an unbiased estimate of the effect of various exposures on depression and anxiety. The suitability of the genetic variant as a proxy can be ascertained by confirming that there is no relationship between variant and outcome in those who do not use the substance. At present, there are suitable instruments for tobacco use, so we use that as a case study. Proof-of-principle Mendelian randomisation studies using these variants have found evidence for a causal effect of smoking on body mass index. Two studies have investigated tobacco and depression using this method, but neither found strong evidence that smoking causes depression or anxiety; evidence is more consistent with a self-medication hypothesis. Mendelian randomisation represents a technique that can aid understanding of exposures that may or may not be causally related to depression and anxiety. As more suitable instruments emerge (including the use of allelic risk scores rather than individual single nucleotide polymorphisms), the effect of other substances can be investigated. Linkage disequilibrium, pleiotropy, and population stratification, which can distort Mendelian randomisation studies, are also discussed. HubMed – depression

Short sleep duration heralds essential tremor: A prospective, population-based study.

Mov Disord. 2013 Jul 11;
Benito-León J, Louis ED, Bermejo-Pareja F

Lewy bodies have been described in the locus coeruleus of some patients with essential tremor (ET), and this brainstem nucleus plays an important role in sleep cycle regulation. Despite this, no studies have investigated the relationship between daily sleep duration and the risk of ET. We determined whether baseline daily sleep duration was associated with an increased risk of incident ET. In this prospective, population-based study of individuals?>?65 years of age (the Neurological Disorders in Central Spain [NEDICES] cohort), participants were evaluated at baseline and 3 years later. At baseline, participants indicated their daily sleep duration as the sum of nighttime sleep and daytime napping. The average daily total sleep duration was grouped into four categories:???5 hours (short sleepers), 6 hours, 7 to 8 hours (reference), and???9 hours (long sleepers) hours. In total, 3,303 participants had a median duration of follow-up of 3.3 years. There were 76 incident ET cases at follow-up. The relative risks for short sleepers and for long sleepers were 2.25 (95% confidence interval [CI], 1.21-4.16; P?=?0.01) and 0.74 (95% CI, 0.41-1.32; P?=?0.31), respectively. After adjustment for potential confounders, including age, sex, educational level, current smoker, current drinker, and depressive symptoms or antidepressant use, the risk remained significantly increased for short sleepers (relative risk, 1.95; 95% CI, 1.03-3.70; P?=?0.04]). The results indicated that short daily sleep duration may be a pre-motor marker for ET. Additional prospective studies are needed to confirm these results, and the biological basis for this association merits additional investigation. © 2013 Movement Disorder Society. HubMed – depression

Risk of Obstructive Sleep Apnea in Patients With Type 2 Diabetes Mellitus.

Fam Med. 2013 July-August; 45(7): 492-500
Cass AR, Alonso WJ, Islam J, Weller SC

Type 2 diabetes mellitus (DM) and obstructive sleep apnea (OSA) share several clinical findings: obesity, hypertension, and impaired glucose tolerance. OSA may be an under-recognized comorbidity of DM. The purpose of this study is to estimate the proportion of patients with type 2 DM at risk for OSA and describe factors associated with that risk.This cross-sectional study enrolled 297 adults, ages 18 years and older, with type 2 DM from a university-based Family Medicine Center. Participants completed a research questionnaire recording sociodemographic information, medical history, and clinical data including medications and hemoglobin A1C. OSA risk was determined using the Berlin Questionnaire. Relationships between risk of OSA and sociodemographic and clinical variables were evaluated using bivariate analyses and covariate adjusted logistic regression models.Thirty-seven participants (12.5%) had a prior diagnosis of OSA. Based on the Berlin Questionnaire, 124 (48.6%) of the remaining patients were classified as high risk for OSA. Patients less than age 60 years were at increased risk for OSA, adjusted OR=2.67 (1.57, 4.54; 95% CI). Non-Hispanic whites, adjusted OR=1.76 (1.01, 3.06; 95% CI), and patients with symptoms of depression, adjusted OR=2.64 (1.60, 4.52; 95% CI), were also at higher risk. Gender and hemoglobin A1C were not associated with increased risk of OSA.Nearly half of adults with type 2 DM may be at high risk for OSA, and many may be undiagnosed. In a primary care setting, the Berlin Questionnaire is an easily applied screening instrument that identifies patients at increased risk of OSA who may benefit from further diagnostic studies and treatment of OSA. HubMed – depression

Impact of Maternal Depression Across the First 6 Years of Life on the Child’s Mental Health, Social Engagement, and Empathy: The Moderating Role of Oxytocin.

Am J Psychiatry. 2013 Jul 12;
Apter-Levy Y, Feldman M, Vakart A, Ebstein RP, Feldman R

OBJECTIVE Maternal depression across the postbirth period has long-term negative consequences for infant development. Little is known of the neurobiological underpinnings, but they could involve oxytocin, a neuropeptide that is dysfunctional in depression and is implicated in birth and parenting. METHOD The authors recruited a community cohort of women with high or low depression scores 2 days after childbirth and measured depression again at 6 and 9 months. When the child was 6, the authors evaluated the families of 46 chronically depressed mothers and 103 mothers reporting no depression since childbirth. The child was assessed for psychiatric diagnoses, social engagement, and empathy. Mother, father, and child were tested for salivary oxytocin level and variation in the rs2254298 single nucleotide polymorphism on the OXTR gene. RESULTS Of the children of the chronically depressed mothers, 61% displayed axis I disorders, mainly anxiety and oppositional defiant disorder, compared with 15% of the children of nondepressed mothers. In the depressed mothers’ families, salivary oxytocin was lower in mothers, fathers, and children, and the children had lower empathy and social engagement levels. The rs2254298 GG homozygous genotype was overrepresented in depressed mothers and their families, and it correlated with lower salivary oxytocin. Presence of a single rs2254298 A allele (GA or AA genotype) in depressed mothers markedly decreased risk of child psychopathology. CONCLUSIONS The negative effect of chronic maternal depression on child social outcomes was related to genetic and peripheral biomarkers of the oxytocin system. This suggests a potential for oxytocin-based interventions. HubMed – depression