Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen\u27s d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen\u27s d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset 21 was associated with a smaller hippocampus (Cohen\u27s d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen\u27s d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen\u27s d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status

A mega-Analysis of genome-wide association studies for major depressive disorder

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P less than 0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P less than 5 × 10−8), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083–53 822 102, minimum P=5.9 × 10−9 at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status

Major depressive disorder

Depression in its various forms is a commonly seen disorder in general practice. Indeed, over 90% of patients suffering from depression are seen, diagnosed and treated in primal) care. The most severe, chronic and complicated cases are referred on to a psychiatrist.peer-reviewe

Tobacco smoking as a risk factor for major depressive disorder : a population-based study

Background : Smoking is disproportionately prevalent among people with psychiatric illness. Aims : To investigate smoking as a risk factor for major depressive disorder. Method : A population-based sample of women was studied using case–control and retrospective cohort study designs. Exposure to smoking was self-reported, and major depressive disorder diagnosed using the Structured Clinical Interview for DSM–IV–TR (SCID–I/NP). Results : Among 165 people with major depressive disorder and 806 controls, smoking was associated with increased odds for major depressive disorder (age-adjusted odds ratio (OR)=1.46, 95% CI 1.03–2.07). Compared with non-smokers, odds for major depressive disorder more than doubled for heavy smokers (>20 cigarettes/day). Among 671 women with no history of major depressive disorder at baseline, 13 of 87 smokers and 38 of 584 non-smokers developed de novo major depressive disorder during a decade of follow-up. Smoking increased major depressive disorder risk by 93% (hazard ratio (HR)=1.93, 95% CI 1.02–3.69); this was not explained by physical activity or alcohol consumption. Conclusions : Evidence from cross-sectional and longitudinal data suggests that smoking increases the risk of major depressive disorder in women

Staging of Major Depressive Disorder

Beekman, A.T.F. [Promotor]Penninx, B.W.J.H. [Promotor]Milaneschi, Y. [Copromotor

Bidirectional Association between Major Depressive Disorder and Gastroesophageal Reflux Disease:Mendelian Randomization Study

Background: Observational research has found a bidirectional relationship between major depressive disorder and gastroesophageal reflux disease; however, the causal association of this relationship is undetermined. Aims: A bidirectional Mendelian randomization study was performed to explore the causal relationships between major depressive disorder and gastroesophageal reflux disease. Methods: For the instrumental variables of major depressive disorder and gastroesophageal reflux disease, 31 and 24 single-nucleotide polymorphisms without linkage disequilibrium (r(2) <= 0.001) were selected from relevant genome-wide association studies, respectively, at the genome-wide significance level (p <= 5 x 10(-8)). We sorted summary-level genetic data for major depressive disorder, gastroesophageal reflux disease, gastroesophageal reflux disease without esophagitis, and reflux esophagitis from meta-analysis study of genome-wide association studies involving 173,005 individuals (59,851 cases and 113,154 non-cases), 385,276 individuals (80,265 cases and 305,011 non-cases), 463,010 individuals (4360 cases and 458,650 non-cases), and 383,916 individuals (12,567 cases and 371,349 non-cases), respectively. Results: Genetic liability to major depressive disorder was positively associated with gastroesophageal reflux disease and its subtypes. Per one-unit increase in log-transformed odds ratio of major depressive disorder, the odds ratio was 1.31 (95% confidence interval [CI], 1.19-1.43; p = 1.64 x 10(-8)) for gastroesophageal reflux disease, 1.51 (95% CI, 1.15-1.98; p = 0.003) for gastroesophageal reflux disease without esophagitis, and 1.21 (95% CI, 1.05-1.40; p = 0.010) for reflux esophagitis. Reverse-direction analysis suggested that genetic liability to gastroesophageal reflux disease was causally related to increasing risk of major depressive disorder. Per one-unit increase in log-transformed odds ratio of gastroesophageal reflux disease, the odds ratio of major depressive disorder was 1.28 (95% confidence interval, 1.11-1.47; p = 1.0 x 10(-3)). Conclusions: This Mendelian randomization study suggests a bidirectional causal relationship between major depressive disorder and gastroesophageal reflux disease

Exploring Risk Factors for Major Depressive Disorder for Female Patients Aged 18 or Older Living in Ocean County, New Jersey

Background: The incidence and prevalence of major depressive disorder has been increasing worldwide, in the United States of America, and on a local level. The population of Ocean County, New Jersey, a predominantly Caucasian, female, middle-aged population, may be at increased risk of developing major depressive disorder. Purpose: To explore the social determinants of health and risk factors for major depressive disorder for female patients aged 18 or older living in Ocean County, New Jersey. Methods: This literature review mainly used PubMed and Scopus for journal articles and utilized governmental databases for additional population data. Results: Analyses conducted on social determinants of health revealed that access to healthcare and attaining higher education were protective factors. Overall, being female, middle-aged, developing comorbid substance use (alcohol or drug use), and being socially isolated were associated with increased risk of developing major depressive disorder. The COVID-19 pandemic has been observed to worsen incidence of major depressive disorder. Conclusion: This research has shown that social determinants of health and risk factors impact the incidence of major depressive disorder in Ocean County, New Jersey. Further research will need to be conducted to further stratify risk in additional counties