Risk Of Major Depressive Disorder Research Articles

The genetic basis of major depressive disorder.

The genetic dissection of major depressive disorder (MDD) ranks as one of the success stories of psychiatric genetics, with genome-wide association studies (GWAS) identifying 178 genetic risk loci and proposing more than 200 candidate genes. However, the GWAS results derive from the analysis of cohorts in which most cases are diagnosed by minimal phenotyping, a method that has low specificity. I review data indicating that there is a large genetic component unique to MDD that remains inaccessible to minimal phenotyping strategies and that the majority of genetic risk loci identified with minimal phenotyping approaches are unlikely to be MDD risk loci. I show that inventive uses of biobank data, novel imputation methods, combined with more interviewer diagnosed cases, can identify loci that contribute to the episodic severe shifts of mood, and neurovegetative and cognitive changes that are central to MDD. Furthermore, new theories about the nature and causes of MDD, drawing upon advances in neuroscience and psychology, can provide handles on how best to interpret and exploit genetic mapping results.

CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor

BackgroundGenetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population.MethodsTwenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software.ResultsOut of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P < 0.05), leading to the odds ratios (ORs) of MDD (2.178) and BPD (2.122), respectively. In contrast, the lower MAFs of ABCB1-rs1045642 were observed in both MDD (0.3599, OR = 0.726) and BPD (0.3700, OR = 0.758) groups than controls (0.4364, P < 0.05). The MDD group had a higher MAF of SCN2A-rs17183814 than controls (0.1743 vs. 0.1207, OR = 1.538, P < 0.05). Moreover, a G-A haplotype composed by CYP2C19-rs4986893 and -rs4244285 was associated with BPD (OR = 1.361, P < 0.01), and the A-G haplotype increased the risks to both MDD (OR = 2.306, P < 0.01) and BPD (OR = 2.332, P < 0.001). The CYP2C19 intermediate metabolizer and poor metabolizer (IM&PM) status was related to the raised risk of both MDD (OR = 1.547, P < 0.01) and BPD (OR = 1.808, P < 0.001).ConclusionOur data indicate that the impaired CYP2C19 metabolism caused by the haplotypes integrated by CYP2C19 alleles might confer the risk to MDD and BPD, whereas the ABCB1-rs1045642 T allele serves as a protective factor.

Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study

Increased prevalence of mental illness has been reported in clinical studies of sex chromosome aneuploidies, but accurate population-based estimates of the prevalence and clinical detection rate of sex chromosome aneuploidies and the associated risks of psychiatric disorders are needed. In this study, we provide such estimates, valid for children and young adults of the contemporary Danish population. We used the iPSYCH2015 case-cohort dataset, which is based on a source population of single-born individuals born in Denmark between May 1, 1981, and Dec 31, 2008. The case sample comprises all individuals from the source population with a diagnosis of any index psychiatric disorder (schizophrenia spectrum disorder, bipolar disorder, major depressive disorder, autism spectrum disorder, or ADHD) by the end of follow-up (Dec 31, 2015), registered in the hospital-based Danish Psychiatric Central Research Register. The cohort consists of individuals randomly selected from the source population, and overlaps with the case sample. Biobanked blood samples for individuals in the case and cohort samples underwent genotyping and quality-control filtering, after which we analysed microarray data to detect sex chromosome aneuploidy karyotypes (45,X, 47,XXX, 47,XXY, and 47,XYY). We estimated the population-valid prevalence of these karyotypes from the cohort sample. Weighted Cox proportional hazards models were used to estimate the risks of each index psychiatric disorder associated with each sex chromosome aneuploidy karyotype, by use of date of first hospitalisation with the index disorder in the respective case group and the cohort as outcome. The clinical detection rate was determined by comparing records of clinical diagnoses of genetic conditions from the Danish National Patient Register with sex chromosome aneuploidy karyotype determined by our study. The assessed sample comprised 119 481 individuals (78 726 in the case sample and 43 326 in the cohort) who had genotyped and quality-control-filtered blood samples, including 64 533 (54%) people of gonadal male sex and 54 948 (46%) of gonadal female sex. Age during follow-up ranged from 0 to 34·7 years (mean 10·9 years [SD 3·5 years]). Information on ethnicity was not available. We identified 387 (0·3%) individuals as carriers of sex chromosome aneuploidies. The overall prevalence of sex chromosome aneuploidies was 1·5 per 1000 individuals. Each sex chromosome aneuploidy karyotype was associated with an increased risk of at least one index psychiatric disorder, with hazard ratios (HRs) of 2·20 (95% CI 1·42-3·39) for 47,XXY; 2·73 (1·25-6·00) for 47,XXX; 3·56 (1·01-12·53) for 45,X; and 4·30 (2·48-7·55) for 47,XYY. All karyotypes were associated with an increased risk of ADHD (HRs ranging from 1·99 [1·24-3·19] to 6·15 [1·63-23·19]), autism spectrum disorder (2·72 [1·72-4·32] to 8·45 [2·49-28·61]), and schizophrenia spectrum disorder (1·80 [1·15-2·80] to 4·60 [1·57-13·51]). Increased risk of major depressive disorder was found for individuals with 47,XXY (1·88 [1·07-3·33]) and 47,XYY (2·65 [1·12-5·90]), and of bipolar disorder for those with 47,XXX (4·32 [1·12-16·62]). The proportion of sex chromosome aneuploidy carriers who had been clinically diagnosed was 93% for 45,X, but lower for 47,XXY (22%), 47,XXX (15%), and 47,XYY (15%). Among carriers, the risk of diagnosis of at least one index psychiatric disorder did not significantly differ between those who had and had not been clinically diagnosed with sex chromosome aneuploidies (p=0·65). Increased risks of psychiatric disorders associated with sex chromosome aneuploidies, combined with low rates of clinical diagnosis of sex chromosome aneuploidies, compromise the adequate provision of necessary health care and counselling to affected individuals and their families, which might be helped by increased application of genetic testing in clinical settings. Lundbeck Foundation and National Institutes of Health.

Women's reproductive traits and major depressive disorder: A two-sample Mendelian randomization study

BackgroundEvidence suggested strong associations between women's reproductive factors and major depressive disorder (MDD), but their causalities are unclear. MethodsUsing female-specific SNPs as genetic instruments obtained from large-scale genome-wide association studies for women's reproductive traits, we designed two-sample univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal effects of women's reproductive traits on MDD. For both univariable MR (UVMR) and multivariable MR (MVMR), the inverse variance weighting estimates were reported as main results. MR-Egger, weighted median, and generalized summary-data-based MR (GSMR) methods for UVMR, and MVMR-Egger and MVMR-robust methods for MVMR were used as sensitivity analyses. Negative control analyses, MVMR of age at first birth (AFB) and age at first sexual intercourse (AFS) on MDD, and sex-combined genetic variants for AFB and AFS were performed to enhance the robustness of our study. ResultsThere was substantial evidence for associations of genetically predicted later age at menarche (AAM) (odds ratio (OR) = 0.97, 95 % confidence interval (CI) = 0.94–0.99, P = 0.007), AFB (OR = 0.91, 95 % CI = 0.86–0.97, P = 0.002) and AFS (OR = 0.70, 95 % CI = 0.60–0.80, P < 0.001) with lower MDD risk in UVMR. After adjustment of BMI and educational attainment using MVMR, we found consistently significant causal effects of AAM (OR = 0.95, 95 % CI = 0.92–0.99, P = 0.006), AFB (OR = 0.88, 95 % CI = 0.84–0.91, P < 0.001) and AFS (OR = 0.71, 95 % CI = 0.64–0.79, P < 0.001) on MDD. ConclusionsOur results provide compelling evidence that early AAM, AFB, and AFS are risk factors for MDD. Promoting the cognition of reproductive health care for women may reduce the risk of MDD.

Overlapping brain correlates of superior cognition among children at genetic risk for Alzheimer’s disease and/or major depressive disorder

Early life adversity (ELA) tends to accelerate neurobiological ageing, which, in turn, is thought to heighten vulnerability to both major depressive disorder (MDD) and Alzheimer’s disease (AD). The two conditions are putatively related, with MDD representing either a risk factor or early symptom of AD. Given the substantial environmental susceptibility of both disorders, timely identification of their neurocognitive markers could facilitate interventions to prevent clinical onset. To this end, we analysed multimodal data from the Adolescent Brain and Cognitive Development study (ages 9–10 years). To disentangle genetic from correlated genetic-environmental influences, while also probing gene-adversity interactions, we compared adoptees, a group generally exposed to substantial ELA, with children raised by their biological families via genetic risk scores (GRS) from genome-wide association studies. AD and MDD GRSs predicted overlapping and widespread neurodevelopmental alterations associated with superior fluid cognition. Specifically, among adoptees only, greater AD GRS were related to accelerated structural maturation (i.e., cortical thinning) and higher MDD GRS were linked to delayed functional neurodevelopment, as reflected in compensatory brain activation on an inhibitory control task. Our study identifies compensatory mechanisms linked to MDD risk and highlights the potential cognitive benefits of accelerated maturation linked to AD vulnerability in late childhood.

Associations of stressful life events with subthreshold depressive symptoms and major depressive disorder: The moderating role of gender

BackgroundStressful life events (SLEs) are high-risk factors for subthreshold depressive symptoms (SDS) and major depressive disorder (MDD). This study sought to assess the association of SLEs with SDS and MDD, with a focus on gender effects. MethodsA total of 4132 participants were recruited from 34 primary health care settings. The Stressful Life Events Screening Questionnaire (SLESQ) was used to measure SLEs that participants had experienced in the past time. The Patient Health Questionnaire 9 (PHQ-9) was used to assess SDS, and the Mini-International Neuropsychiatry Interview (MINI) depression module was used to assess the diagnosis of MDD by trained psychiatrists. ResultsIn our sample (N = 4132), exposure to any SLEs was more common in individuals with SDS and MDD than in non-depressed population, and the proportion of emotional abuse was relatively high (SDS: 10.6 %; MDD: 33.9 %). After adjusting for control variables, people who experienced SLEs were at a higher risk of SDS and MDD. For males, those experiencing only one event were not at a higher risk of SDS (P = 0.061). For individuals who had experienced multiple SLEs, the association between SLEs and SDS was stronger in females than males. However, the association between SLEs and MDD was stronger in males than females. LimitationsThe cross-sectional study design and self-reported SLEs. ConclusionsSLEs were associated with the increased risks of SDS and MDD. The associations of SLEs with SDS were more robust for females than males. In contrast, the association between SLEs and MDD was stronger in males than females.

The Risk of Major Depressive Disorder Due to Cataracts among the Korean Elderly Population: Results from the Korea National Health and Nutrition Examination Survey (KNHANES) in 2016 and 2018.

Cataracts and major depressive disorder (MDD) both have high prevalence, representing for major health burdens globally. In this study, we examined the risk of MDD due to cataracts. Data from the 2016 to 2018 Korea National Health and Nutrition Examination Survey (KNHANES) were used, including 4122 participants. Logistic regression analysis was performed to evaluate the odds ratio for MDD in association with cataracts. Controlled variables were age, gender, smoking, dyslipidemia and mobility. Subgroup analysis was performed with stratification by gender. The results reveal that cataracts are significantly correlated with MDD. Elderly people with cataracts were found to be more likely to develop MDD compared to those without cataracts (adjusted odds ratio: 1.654; 95% CI = 1.197-2.286). In subgroup analysis, men (adjusted odds ratio: 2.631; 95% CI = 1.247-5.551) were found to be more likely to develop MDD than women (adjusted odds ratio: 1.510; 95% CI = 1.061-2.150). Cataracts may be a risk factor for MDD in the elderly, especially among the male population.

Family coaggregation of type 1 diabetes mellitus, major depressive disorder, attention-deficiency hyperactivity disorder and autism spectrum disorder in affected families: a nationwide study.

This study aimed to examine the risk of T1D, major depressive disorder (MDD), attention-deficiency hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), in first-degree relatives (FDRs) of patients with T1D. We enrolled 24,555 FDRs of individuals with T1D and 1:4 matched controls (N = 98,220) based on age and sex using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. Poisson regression analyses were performed to estimate the risks of MDD, attention-deficiency hyperactivity disorder (ADHD), and autism spectrum disorder among the FDRs. Finally, we assessed the impact of DKA in the familial coaggregation. After adjusting for demographic characteristics, FDRs of individuals with T1D had higher risk of T1D (reported as relative risk with 95% confidence interval: 46.07, 33.36-63.63) and MDD (1.17, 1.04-1.32) than controls. Stratified by sex, female FDRs had increased risk of MDD (1.30, 1.13-1.51), while male FDRs had increased risk of ADHD (1.21, 1.01-1.44). Stratified by kinship, parents of individuals with T1D had increased risk of MDD (1.24, 1.06-1.44); offspring of individuals with T1D had increased risk of ADHD (1.41, 1.11-1.79). Importantly, FDRs of individuals with T1D and DKA had higher risk of MDD (1.35, 1.11-1.64) and ADHD (1.40, 1.07-1.82) than controls; however, such risks were not observed in FDRs of individuals with T1D but without DKA. The individual risks of T1D, MDD, and ADHD were increased in families that included patients with T1D, and DKA might play a role in such coaggregation with MDD and ADHD. Future studies are warranted to investigate the underlying mechanisms.

A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease

Among candidate neurodegenerative/neuropsychiatric risk-predictive biomarkers, platelet count, mean platelet volume and platelet distribution width have been associated with the risk of major depressive disorder (MDD), Alzheimer's disease (AD) and Parkinson's disease (PD) through epidemiological and genomic studies, suggesting partial co-heritability. We exploited these relationships for a multi-trait association analysis, using publicly available summary statistics of genome-wide association studies (GWASs) of all traits reported above. Gene-based enrichment tests were carried out, as well as a network analysis of significantly enriched genes. We analyzed 4,540,326 single nucleotide polymorphisms shared among the analyzed GWASs, observing 149 genome-wide significant multi-trait LD-independent associations (p < 5 × 10-8) for AD, 70 for PD and 139 for MDD. Among these, 27 novel associations were detected for AD, 34 for PD and 40 for MDD. Out of 18,781 genes with annotated variants within ±10 kb, 62 genes were enriched for associations with AD, 70 with PD and 125 with MDD (p < 2.7 × 10-6). Of these, seven genes were novel susceptibility loci for AD (EPPK1, TTLL1, PACSIN2, TPM4, PIF1, ZNF689, AZGP1P1), two for PD (SLC26A1, EFNA3) and two for MDD (HSPH1, TRMT61A). The resulting network showed a significant excess of interactions (enrichment p = 1.0 × 10-16). The novel genes that were identified are involved in the organization of cytoskeletal architecture (EPPK1, TTLL1, PACSIN2, TPM4), telomere shortening (PIF1), the regulation of cellular aging (ZNF689, AZGP1P1) and neurodevelopment (EFNA3), thus, providing novel insights into the shared underlying biology of brain disorders and platelet parameters.

The relationship of major depressive disorder with Crohn's disease activity

IntroductionCrohn's disease (CD) has been related to an increased prevalence of psychiatric disorders and suicide risk (SR). However, the nature of their relationship still deserves clarification. The aim of this study is to assess the prevalence of major depressive disorder (MDD) in patients with CD, and to investigate the relationship between MDD and CD outcomes. MethodsA cross-sectional study involving CD patients was performed. CD activity was evaluated by the Harvey-Bradshaw index and CD phenotype by the Montreal classification. The presence of MDD was assessed by the Patient Health Questionnaire score-9 (PHQ-9). Sociodemographic data and other characteristics were retrieved from electronic medical records. Results283 patients with CD were included. The prevalence of MDD was 41.7%. Females had a risk of MDD 5.3 times greater than males. CD disease duration was inversely correlated with MDD severity. Individuals with active CD were more likely to have MDD (OR = 796.0; 95% CI 133.7‒4738.8) than individuals with CD remission. MDD was more prevalent in inflammatory behavior (45.5%) and there were no statistical differences regarding the disease location. 19.8% of the sample scored positive for SR. ConclusionThe present results support data showing an increased prevalence of MDD in individuals with CD. Additionally, it indicates that MDD in CD might be related to the activity of CD. Prospective studies are warranted to confirm these results and to address whether MDD leads to CD activity, CD activity leads to MDD or both ways are existent.

Impact of Prediagnosis Risk of Major Depressive Disorder and Health-Related Quality of Life on Treatment Choice for Stage II-III Rectal Cancer

We hypothesized that depressive symptoms and health-related quality of life (HRQOL) reported by patients before their cancer diagnoses would be associated with treatment choice for stage II and III rectal cancer, specifically whether patients underwent surgery. The Surveillance, Epidemiology, and End Results and Medicare Health Outcomes Survey linked data set was used to identify patients with stage II-III rectal adenocarcinoma diagnosed between 2004 and 2013 who had completed the health outcomes survey within 36 months before their cancer diagnoses. Risk for major depressive disorder (MDD) was determined on the basis of responses to screening questions for depressive disorders. HRQOL was assessed using the Mental Component Summary and Physical Component Summary of the 36-Item Short Form Survey and Veterans RAND 12-Item Health Survey. Using univariable and multivariable analyses, we assessed for associations between health survey responses and ultimate treatment modality. We identified 142 evaluable patients, of whom 109 (76.8%) underwent surgery. Thirty patients (21.1%) met criteria for being at risk for MDD before their cancer diagnoses. Patients at risk for MDD underwent surgery less often than those not at risk (P = .0499), and this association strengthened after adjusting for patient characteristics (odds ratio, 0.17; 95% CI, 0.04 to 0.82; P = .027). There was a nonsignificant trend between higher Mental Component Summary scores (indicating higher self-reported mental HRQOL) and increased frequency of undergoing surgery (P = .081). There were no significant associations between the Physical Component Summary and treatment modality. In Medicare beneficiaries with stage II-III rectal cancer, those at risk for MDD underwent standard-of-care treatment with surgery less frequently. Further studies are warranted to assess the effect of mental health on clinical decision making in this patient population.

Prediction models for depression risk among older adults: systematic review and critical appraisal.

To provide an overview of prediction models for the risk of major depressive disorder (MDD) among older adults. We conducted a systematic review combined with a meta-analysis and critical appraisal of published studies on existing geriatric depression risk models. The systematic search screened 23,378 titles and abstracts; 14 studies including 20 prediction models were included. A total of 16 predictors were selected in the final model at least twice. Age, physical health, and cognitive function were the most common predictors. Only one model was externally validated, two models were presented with a complete equation, and five models examined the calibration. We found substantial heterogeneity in predictor and outcome definitions across models; important methodological information was often missing. All models were rated at high or unclear risk of bias, primarily due to methodological limitations. The pooled C-statistics of 12 prediction models was 0.83 (95%CI=0.77-0.89). The usefulness of all models remains unclear due to several methodological limitations. Future studies should focus on methodological quality and external validation of depression risk prediction models.

Improved lifestyle is associated with improved depression, anxiety and well-being over time in UK healthcare professionals during the COVID-19 pandemic: insights from the CoPE-HCP cohort study

BackgroundOne potential modifiable factor to improve the mental health of healthcare professionals (HCPs) during the pandemic is lifestyle.AimsThis study aimed to assess whether an improved lifestyle during the pandemic is...

Smaller rostral cingulate volume and psychosocial correlates in veterans at risk for suicide

Suicide research/clinical work remain in dire need of effective tools that can better predict suicidal behavior. A growing body of literature has started to focus on the role that neuroimaging may play in helping explain the path towards suicide. Specifically, structural alterations of rostral anterior cingulate cortex (rost-ACC) may represent a biological marker and/or indicator of suicide risk in Major Depressive Disorder (MDD). Furthermore, the construct of “grit,” defined as perseverance for goal-attainment and shown to be associated with suicidality, is modulated by rost-ACC. The aim was to examine relationships among rost-ACC gray matter volume, grit, and suicidality in U.S. Military Veterans. Participants were age-and-sex-matched Veterans with MDD: with suicide attempt (MDD+SA:n = 23) and without (MDD-SA:n = 37). Groups did not differ in depression symptomatology. Participants underwent diagnostic interview, clinical symptom assessment, and 3T-MRI-scan. A Group (SA-vs.-No-SA) x Cingulate-region (rostral-caudal-posterior) x Hemisphere (left-right) mixed-model-multivariate-ANOVA was conducted. Left-rost-ACC was significantly smaller in MDD+SA, Group x Cingulate-region x Hemisphere-interaction. Lower grit and less left-rost-ACC gray matter each predicted suicide attempt history, but grit level was a more robust predictor of SA. Both structural alterations of rost-ACC and grit level represent potentially valuable tools for suicide risk assessment.

Association of circadian rhythms with brain disorder incidents: a prospective cohort study of 72242 participants

Circadian rhythm disruption (CRD) is a shared characteristic of various brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and major depression disorder (MDD). Disruption of circadian rhythm might be a risk factor for brain disorder incidents. From 7-day accelerometry data of 72,242 participants in UK Biobank, we derived a circadian relative amplitude variable, which to some extent reflected the degree of circadian rhythm disruption. Records of brain disorder incidents were obtained from a wide range of health outcomes across self-report, primary care, hospital inpatient data, and death data. Using multivariate Cox proportional hazard ratio regression, we created two models adjusting for different covariates. Then, linear correlations between relative amplitude and several brain morphometric measures were examined in participants with brain MRI data. After a median follow-up of around 6.1 years, 72,242 participants were included in the current study (female 54.9%; mean age 62.1 years). Individuals with reduced relative amplitude had increasing risk of all-cause dementia (Hazard ratio 1.23 [95% CI 1.15 to 1.31]), PD (1.33 [1.25 to 1.41]), stroke (1.13 [1.06 to 1.22]), MDD (1.18 [1.13 to 1.23]), and anxiety disorder (1.14 [1.09 to 1.20]) in fully adjusted models. Additionally, significant correlations were found between several cortical regions and white matter tracts and relative amplitude that have been linked to dementia and psychiatric disorders. We confirm CRD to be a risk factor for various brain disorders. Interventions for regulating circadian rhythm may have clinical relevance to reducing the risk of various brain disorders.

Mendelian randomization investigation highlights different roles of selenium status in mental disorders

Observational studies have suggested a relationship between selenium status and mental disorders (MDs). However, it remains unclear whether selenium status was causally associated with MDs. Thus, we performed a two-sample Mendelian randomization analysis using genome-wide association studies (GWAS) summary statistics to investigate the causal effects of selenium levels on seven MDs, including schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), bipolar disorder (BD), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and panic disorder (PD). Strong genetic instruments of blood selenium (n = 9) and blood-toenail selenium (n = 12) were applied to the above seven MDs GWAS datasets from Psychiatric Genomics Consortium, which were further replicated in the FinnGen Biobank. The inverse-variance weighted method was employed to calculate the causal effects. The results showed that genetically predicted blood selenium levels were associated with a decreased risk of schizophrenia (odds ratio [OR] = 0.90, 95% CI: 0.87–0.95) and AN (OR = 0.87, 95% CI: 0.77–0.97). However, both blood and blood-toenail selenium levels were linked to an increased risk of MDD (blood: OR = 1.08, 95% CI: 1.05–1.12; blood-toenail: OR = 1.08, 95% CI: 1.04–1.13) and ASD (blood: OR = 1.11, 95% CI: 1.05–1.17; blood-toenail: OR = 1.13, 95% CI: 1.05–1.21), respectively. No obvious associations were found between selenium levels and BD as well as ADHD. Our findings highlighted a protective role of selenium in SZ and AN, while a risk effect in MDD and ASD. Further studies are required to verify the underlying mechanism mediating the unequal effects of Se on different MDs, which will pave a new path for the intervention of MDs.

Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: A Specific Hormonal or a General Autoimmune Comorbidity.

Background: The hypothalamus-pituitary-thyroid axis coordinates brain development and postdevelopmental function. Thyroid hormone (TH) variations, even within the normal range, have been associated with the risk of developing common psychiatric disorders, although the underlying mechanisms remain poorly understood. Methods: To get new insight into the potentially shared mechanisms underlying thyroid dysfunction and psychiatric disorders, we performed a comprehensive analysis of multiple phenotypic and genotypic databases. We investigated the relationship of thyroid disorders with depression, bipolar disorder (BIP), and anxiety disorders (ANXs) in 497,726 subjects from U.K. Biobank. We subsequently investigated genetic correlations between thyroid disorders, thyrotropin (TSH), and free thyroxine (fT4) levels, with the genome-wide factors that predispose to psychiatric disorders. Finally, the observed global genetic correlations were furthermore pinpointed to specific local genomic regions. Results: Hypothyroidism was positively associated with an increased risk of major depressive disorder (MDD; OR = 1.31, p = 5.29 × 10-89), BIP (OR = 1.55, p = 0.0038), and ANX (OR = 1.16, p = 6.22 × 10-8). Hyperthyroidism was associated with MDD (OR = 1.11, p = 0.0034) and ANX (OR = 1.34, p = 5.99 × 10-⁶). Genetically, strong coheritability was observed between thyroid disease and both major depressive (rg = 0.17, p = 2.7 × 10-⁴) and ANXs (rg = 0.17, p = 6.7 × 10-⁶). This genetic correlation was particularly strong at the major histocompatibility complex locus on chromosome 6 (p < 10-⁵), but further analysis showed that other parts of the genome also contributed to this global effect. Importantly, neither TSH nor fT4 levels were genetically correlated with mood disorders. Conclusions: Our findings highlight an underlying association between autoimmune hypothyroidism and mood disorders, which is not mediated through THs and in which autoimmunity plays a prominent role. While these findings could shed new light on the potential ineffectiveness of treating (minor) variations in thyroid function in psychiatric disorders, further research is needed to identify the exact underlying molecular mechanisms.

Impact of depression on the quality of sleep and immune functions in patients with coronary artery disease

BackgroundThe risk of major depressive disorder (MDD) and insomnia is higher in patients with coronary heart disease (CHD) than in the general population. In addition, immune inflammation may be a...

Sleep to Reduce Incident Depression Effectively (STRIDE): study protocol for a randomized controlled trial comparing stepped-care cognitive-behavioral therapy for insomnia versus sleep education control to prevent major depression

BackgroundPrevention of major depressive disorder (MDD) is a public health priority. Strategies targeting individuals at elevated risk for MDD may guide effective preventive care. Insomnia is a reliable precursor to depression, preceding half of all incident and relapse cases. Thus, insomnia may serve as a useful entry point for preventing MDD. Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but widespread implementation is limited by a shortage of trained specialists. Innovative stepped-care approaches rooted in primary care can increase access to CBT-I and reduce rates of MDD.Methods/designWe propose a large-scale stepped-care clinical trial in the primary care setting that utilizes a sequential, multiple assignment, randomized trial (SMART) design to determine the effectiveness of dCBT-I alone and in combination with clinician-led CBT-I for insomnia and the prevention of MDD incidence and relapse. Specifically, our care model uses digital CBT-I (dCBT-I) as a first-line intervention to increase care access and reduce the need for specialist resources. Our proposal also adds clinician-led CBT-I for patients who do not remit with first-line intervention and need a more personalized approach from specialty care. We will evaluate negative repetitive thinking as a potential treatment mechanism by which dCBT-I and CBT-I benefit insomnia and depression outcomes.DiscussionThis project will test a highly scalable model of sleep care in a large primary care system to determine the potential for wide dissemination and implementation to address the high volume of population need for safe and effective insomnia treatment and associated prevention of depression.Trial registrationClinicalTrials.gov NCT03322774. Registered on October 26, 2017

Polygenic risk scores for schizophrenia and major depression are associated with socio-economic indicators of adversity in two British community samples

Schizophrenia (SCZ) and major depressive disorder (MDD) are complex psychiatric disorders which contribute substantially to the global burden of disease. Both psychopathologies are heritable with some genetic overlap between them. Importantly, SCZ and MDD have also been found to be associated with environmental risk factors. However, rather than being independent of genetic influences, exposure to environmental risk factors may be under genetic control, known as gene-environment correlation (rGE). In this study we investigated rGE in relation to polygenic risk scores for SCZ and MDD in adults, derived from large genome-wide association studies, across two different British community samples: Understanding Society (USoc) and the National Child Development Study (NCDS). We tested whether established environmental risk factors for SCZ and/or MDD are correlated with polygenic scores in adults and whether these associations differ between the two disorders and cohorts. Findings partially overlapped between disorders and cohorts. In NCDS, we identified a significant correlation between the genetic risk for MDD and an indicator of low socio-economic status, but no significant findings emerged for SCZ. In USoc, we replicated associations between indicators of low socio-economic status and the genetic propensity for MDD. In addition, we identified associations between the genetic susceptibility for SCZ and being single or divorced. Results across both studies provide further evidence that the genetic risk for SCZ and MDD were associated with common environmental risk factors, specifically MDD’s association with lower socio-economic status.