An epidemiological survey on personality disorder in Andalusia (the PISMA-ep PD study).

BACKGROUND: Despite a significant clinical and social burden, there is a relative scarcity of epidemiological studies on Personality Disorder (PD). AIM: To determine the current prevalence of PD and the psychosocial correlates associated with this in the Andalusian population. METHOD: We carried out a cross-sectional population mental-health survey in Andalusia, southern Spain. Thus, 4,518 randomly selected participants were interviewed following sampling using different standard stratification levels. We used the Spanish version of the SAPAS to estimate PD prevalence. In addition, a full battery of other instruments was utilized to explore global functionality, childhood abuse, maltreatment, threatening life events, personality traits (neuroticism, impulsivity and paranoia), medical and psychiatric comorbidities, family history of psychological problems and other potential risk factors for PD. RESULTS: PD prevalence (10.8%; 95% CI [9.8, 11.7]) and ran two different multivariate models for PD. We obtained the highest PD prevalence in those affected by any mental disorder plus those reporting having suffered childhood abuse, particularly sexual abuse. Additional potential risk factors or correlates of PD identified were: younger age, lower levels of functioning, less social support, poorer general health, having suffered maltreatment, threatening life events, higher suicidal risk scores and higher levels of both neuroticism and impulsivity. CONCLUSIONS: This study reports PD prevalence and risk correlates in consonance with similar findings reported in other Western populations. However, longitudinal studies are needed to elicit a more thorough group of prospective determinants of PD.

Antibacterial and Cytotoxic Study of Hybrid Films Based on Polypropylene and NiO or NiFe2O4 Nanoparticles.

This study presents an in vitro analysis of the bactericidal and cytotoxic properties of hybrid films containing nickel oxide (NiO) and nickel ferrite (NiFe2O4) nanoparticles embedded in polypropylene (PP). The solvent casting method was used to synthesize films of PP, PP@NiO, and PP@NiFe2O4, which were characterized by different spectroscopic and microscopic techniques. The X-ray diffraction (XRD) patterns confirmed that the small crystallite sizes of NiO and NiFe2O4 NPs were maintained even after they were incorporated into the PP matrix. From the Raman scattering spectroscopy data, it was evident that there was a significant interaction between the NPs and the PP matrix. Additionally, the Scanning Electron Microscopy (SEM) analysis revealed a homogeneous dispersion of NiO and NiFe2O4 NPs throughout the PP matrix. The incorporation of the NPs was observed to alter the surface roughness of the films; this behavior was studied by atomic force microscopy (AFM). The antibacterial properties of all films were evaluated against Pseudomonas aeruginosa (ATCC®: 43636™) and Staphylococcus aureus (ATCC®: 23235™), two opportunistic and nosocomial pathogens. The PP@NiO and PP@ NiFe2O4 films showed over 90% bacterial growth inhibition for both strains. Additionally, the effects of the films on human skin cells, such as epidermal keratinocytes and dermal fibroblasts, were evaluated for cytotoxicity. The PP, PP@NiO, and PP@NiFe2O4 films were nontoxic to human keratinocytes. Furthermore, compared to the PP film, improved biocompatibility of the PP@NiFe2O4 film with human fibroblasts was observed. The methodology utilized in this study allows for the production of hybrid films that can inhibit the growth of Gram-positive bacteria, such as S. aureus, and Gram-negative bacteria, such as P. aeruginosa. These films have potential as coating materials to prevent bacterial proliferation on surfaces.

Scanning Tunneling Microscopy Study of Lipoic Acid, Mannose, and cRGD@AuNPs Conjugates.

The functionalization of AuNPs with different biological elements was achieved to investigate their possibility in biomedical applications such as drug delivery, vaccine development, sensing, and imaging. Biofunctionalized AuNPs are pursued for applications such as drug delivery, vaccine development, sensing, and imaging. In this study, AuNPs with diameters of 20 nm were functionalized with lipoic acid, mannose, or the cRGD peptide. By using UV-vis spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy, and scanning tunneling microscopy techniques, we showed that AuNPs can be functionalized by these biomolecules in a reliable way to obtain conjugates to explore potential biomedical applications. In particular, we demonstrate that the STM technique can be employed to analyze biofunctionalized AuNPs, and the obtained information can be valuable in the design of biomedical applications.

Treatment of COVID-19 during the Acute Phase in Hospitalized Patients Decreases Post-Acute Sequelae of COVID-19.

BACKGROUND: The post-acute sequelae of SARS-CoV-2 (PASC) infection have caused a significant impact on our health system, but there is limited evidence of approved drugs focused on its prevention. Our objective was to identify risk factors that can determine the presence of PASC, with special attention to the treatment received in the acute phase, and to describe the profile of persistent symptoms in a multidisciplinary Post-Coronavirus Disease-19 (COVID-19) Unit. METHODS: This one-year prospective observational study included patients following an acute COVID-19 infection, irrespective of whether they required hospital admission. A standardized symptom questionnaire and blood sampling were performed at the first follow-up visit, and demographic and clinical electronic data were collected. We compared subjects with PASC with those who had fully recovered. Multivariate logistic regression was performed to identify factors associated with PASC in hospitalized patients, and Kaplan-Meier curves were used to assess duration of symptoms according to disease severity and treatments received in the acute phase. RESULTS: 1966 patients were evaluated; 1081 had mild disease, 542 moderate and 343 severe; around one third of the subjects had PASC, and were more frequently female, with obesity, asthma, and eosinophilia during acute COVID-19 disease. Patients who received treatment with dexamethasone and remdesivir during the course of the acute illness showed a lower median duration of symptoms, compared with those who received none of these treatments. CONCLUSION: Treatment with dexamethasone and/or remdesivir may be useful to reduce the impact of PASC secondary to SARS-CoV-2 infection. In addition, we identified female gender, obesity, asthma, and disease severity as risk factors for having PASC.

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations.

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study-and most other large-scale human genetics studies-was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10-6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.

Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia.

Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the catechol-O-methyltransferase (COMT) Val105/158Met polymorphism in the aetiology of schizophrenia since it alters the dopamine metabolism. A case−control study of 141 patients and 142 controls was conducted to analyse the polymorphism, the prevalence of anti-T. gondii IgG, and their interaction on the risk for schizophrenia. IgG were detected by ELISA, and genotyping was performed with TaqMan Real-Time PCR. Although no association was found between any COMT genotype and schizophrenia, we found a significant association between T. gondii seropositivity and the disorder (χ2 = 11.71; p-value < 0.001). Furthermore, the risk for schizophrenia conferred by T. gondii was modified by the COMT genotype, with those who had been exposed to the infection showing a different risk compared to that of nonexposed ones depending on the COMT genotype (χ2 for the interaction = 7.28, p-value = 0.007). This study provides evidence that the COMT genotype modifies the risk for schizophrenia conferred by T. gondii infection, with it being higher in those individuals with the Met/Met phenotype, intermediate in heterozygous, and lower in those with the Val/Val phenotype.

Interaction Effect between Physical Activity and the BDNF Val66Met Polymorphism on Depression in Women from the PISMA-ep Study.

The relationship between depression and the Val66Met polymorphism at the brain-derived neurotrophic factor gene (BDNF), has been largely studied. It has also been related to physical activity, although the results remain inconclusive. The aim of this study is to investigate the relationship between this polymorphism, depression and physical activity in a thoroughly characterised sample of community-based individuals from the PISMA-ep study. A total of 3123 participants from the PISMA-ep study were genotyped for the BDNF Val66Met polymorphism, of which 209 had depression. Our results are in line with previous studies reporting a protective effect of physical activity on depression, specifically in light intensity. Interestingly, we report a gene-environment interaction effect in which Met allele carriers of the BDNF Val66Met polymorphism who reported more hours of physical activity showed a decreased prevalence of depression. This effect was observed in the total sample (OR = 0.95, 95%CI = 0.90-0.99, p = 0.027) and was strengthened in women (OR = 0.93, 95%CI = 0.87-0.98, p = 0.019). These results highlight the potential role of physical activity as a promising therapeutic strategy for preventing and adjuvant treatment of depression and suggest molecular and genetic particularities of depression between sexes.

Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals.

Depression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = [0.65, 0.76]). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesity-associated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals.

The role of the FTO gene in the relationship between depression and obesity. A systematic review.

Depression and obesity are major global health problems that frequently co-occur. The FTO gene has one of the strongest links with obesity and high body mass index (BMI) in humans. Besides, this gene is highly expressed in the brain, may play a role in the nervous system, and could confer risk for depression, although scarce literature is available in this respect. We perform a systematic review of the relationship between FTO and both conditions. We selected original articles with observational design or reviews, where depression was assessed with ICD-10, DSM-5 or previous versions, published from 2012 (when the first related paper was published) to November 2020, performed in adults, in English or Spanish and having an optimal methodological quality (evaluated with SIGN checklist). Five original studies were finally included. The results regarding the role of FTO in depression-obesity comorbidity were inconclusive. This leads us to endorse further research covering the role of this gene on both conditions, emphasising a more precise characterization of depression, in order to confirm this role.

Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.

Gadolinium-containing carbon nanomaterials for magnetic resonance imaging: Trends and challenges.

Gadolinium-containing carbon nanomaterials are a new class of contrast agent for magnetic resonance imaging. They are characterized by a superior proton relaxivity to any current commercial gadolinium contrast agent and offer the possibility to design multifunctional contrasts. Intense efforts have been made to develop these nanomaterials because of their potential for better results than the available gadolinium contrast agents. The aim of the present work is to provide a review of the advances in research on gadolinium-containing carbon nanomaterials and their advantages over conventional gadolinium contrast agents. Due to their enhanced proton relaxivity, they can provide a reliable imaging contrast for cells, tissues or organs with much smaller doses than currently used in clinical practice, thus leading to reduced toxicity (as shown by cytotoxicity and biodistribution studies). Their active targeting capability allows for improved MRI of molecular or cellular targets, overcoming the limited labelling capability of available contrast agents (restricted to physiological irregularities during pathological conditions). Their potential of multifunctionality encompasses multimodal imaging and the combination of imaging and therapy.

Associations of major depressive disorder with chronic physical conditions, obesity and medication use: Results from the PISMA-ep study.

BACKGROUND: Life expectancy of people with depression is on average 15 years less than that of the general population. This excess of mortality is largely attributed to a deteriorated physical health. Evidence about the association between major depressive disorder (MDD) and physical health is still lacking in some areas. The aim of this study was to explore the association between MDD and physical health-related variables in southern Spain. METHODS: The PISMA-ep is a cross-sectional study based on community-dwelling adult population. Our main outcome was current prevalence of MDD. Independent variables explored were: lifetime prevalence of twenty-one chronic physical conditions (CPCs), anthropometric measures (height, weight, body max index, and hip and waist circumferences), general health status, and medication use. RESULTS: MDD was significantly associated with any CPC (OR = 2.60; 95% CI: 2.01-3.35; p < 0.001). Increases in BMI were associated with MDD in women (OR=1.08; 95% CI: 1.05-1.11; p < 0.001), but not in men (OR=0.99; 95% CI: 0.95-1.05; p = 0.916). Variables associated with MDD in the multivariate model were: female gender, obesity, general health status, cancer, peptic ulcer, tinnitus and vertigo. 21.4% of participants with MDD received antidepressant treatment. CONCLUSIONS: MDD is associated with CPCs, obesity, and increased use of medication. The high rates of comorbidity between MDD and CPCs call for a more holistic management of patients in the clinical practice. The low rate of antidepressant use may be indicating underdiagnosis. Anthropometric variables were differently associated with MDD depending on gender, suggesting a strong influence of psychosocial factors.

Preparation and Characterization of a Novel Organic Semiconductor Indacenedithiophene Derivative and the Corresponding Langmuir-Blodgett Thin Films.

The synthesis of a novel indacenedithiophene derivative (IDT-DPA) is described, which exhibits semiconducting behavior. Its properties were measured by means of UV-visible and fluorescence spectroscopies using toluene as solvent. An extinction molar coefficient of 2.05×104 M-1 cm-1 and a Stokes shift of 50 nm were obtained. A theoretical study was performed using the density functional theory, from which HOMO-LUMO band gap of 1.711 eV was calculated. IDT-DPA was deposited on the water-air interface to form Langmuir monolayers. π-A curves and hysteresis were measured showing reversibility behavior. The monolayers were transferred to glass substrates as Langmuir-Blodgett thin films. Their morphological properties were characterized by using scanning electron and atomic force microscopy, which showed that the films tend to form clusters with a homogeneous distribution. Absorption and emission spectra of the films were measured, from which the optical band gap and Stocks shift were derived. Based on the electronic properties and light emission spectra of IDT-DPA, this compound can be proposed for the applications in organic lightemitting diodes and other organic semiconductor devices.

Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, with a high prevalence and a presumed high heterogeneity. Copy number variants (CNVs) could contribute to the heritable component of risk, but the two previous genome-wide association studies of rare CNVs did not report significant findings. METHODS: In this meta-analysis of four cohorts (5780 patients and 6626 control subjects), we analyzed the association of MDD to 1) genome-wide burden of rare deletions and duplications, partitioned by length (<100 kb or >100 kb) and other characteristics, and 2) individual rare exonic CNVs and CNV regions. RESULTS: Patients with MDD carried significantly more short deletions than control subjects (p = .0059) but not long deletions or short or long duplications. The confidence interval for long deletions overlapped with that for short deletions, but long deletions were 70% less frequent genome-wide, reducing the power to detect increased burden. The increased burden of short deletions was primarily in intergenic regions. Short deletions in cases were also modestly enriched for high-confidence enhancer regions. No individual CNV achieved thresholds for suggestive or significant association after genome-wide correction. p values < .01 were observed for 15q11.2 duplications (TUBGCP5, CYFIP1, NIPA1, and NIPA2), deletions in or near PRKN or MSR1, and exonic duplications of ATG5. CONCLUSIONS: The increased burden of short deletions in patients with MDD suggests that rare CNVs increase the risk of MDD by disrupting regulatory regions. Results for longer deletions were less clear, but no large effects were observed for long multigenic CNVs (as seen in schizophrenia and autism). Further studies with larger sample sizes are warranted.

Physical exercise and body mass index as correlates of major depressive disorder in community-dwelling adults: Results from the PISMA-ep study.

BACKGROUND: Major Depressive Disorder (MDD) is one of the most prevalent and disabling mental disorders. Sedentarism and obesity are recognized risk factors for MDD. Physical exercise has shown beneficial effects on mental health and there is an increasing awareness of its potential as a therapeutic and preventive tool for depression. No epidemiological studies have explored the role of physical activity and obesity as potential correlates of MDD in the Spanish population. The aim of this study was to explore whether MDD was associated with two strongly linked variables: physical exercise and body mass index. METHODS: The PISMA-ep is a cross-sectional community-based study carried out in Andalusia, southern Spain. Main outcome was current prevalence of MDD, measured through face-to-face interviews using the Mini-International Neuropsychiatric Interview (MINI). Independent variables explored were physical exercise and its intensity, Body Mass Index (BMI), BMI categories (underweight, normal weight, overweight and obesity), hip and waist circumferences, general health status measured with the SF12 questionnaire, and sociodemographic factors. RESULTS: Physical exercise was inversely associated with MDD, acting as a protective factor. Higher intensity of exercise strengthened this association. Four variables were independently associated with MDD in the multivariate association model: female sex, physical exercise, general health status and BMI. CONCLUSION: MDD was associated with poorer health status, higher BMI and reduced physical activity. Physical exercise should be considered as a potential intervention for the treatment and prevention of MDD in clinical and public health settings.

Reduction in the levels of CoQ biosynthetic proteins is related to an increase in lifespan without evidence of hepatic mitohormesis.

Mitohormesis is an adaptive response induced by a mild mitochondrial stress that promotes longevity and metabolic health in different organisms. This mechanism has been proposed as the cause of the increase in the survival in Coq7+/- (Mclk1+/-) mice, which show hepatic reduction of COQ7, early mitochondrial dysfunction and increased oxidative stress. Our study shows that the lack of COQ9 in Coq9Q95X mice triggers the reduction of COQ7, COQ6 and COQ5, which results in an increase in life expectancy. However, our results reveal that the hepatic CoQ levels are not decreased and, therefore, neither mitochondrial dysfunction or increased oxidative stress are observed in liver of Coq9Q95X mice. These data point out the tissue specific differences in CoQ biosynthesis. Moreover, our results suggest that the effect of reduced levels of COQ7 on the increased survival in Coq9Q95X mice may be due to mitochondrial mechanisms in non-liver tissues or to other unknown mechanisms.

A Cross-Sectional Study on the Prevalence and Risk Correlates of Mental Disorders: The GRANADΣP Study.

This is a cross-sectional study of participants from a population census living in the province of Granada (Spain). A total of 1176 persons were contacted, 367 (31%) refused and 54 (6.7%) needed substitution. A final sample of 809 participants (response rate, 69.3%) were screened for mental disorder (MD) using the MINI International Neuropsychiatric Interview, a comprehensive interview validated to generate diagnoses compatible with ICD-10/DSM-4 criteria. Current (1-month) prevalence for any MD was 11.3% (95% confidence interval [CI], 9.7%-13.4%; affective 8.2%, anxiety 9.6%, psychotic 2.1%, addiction 1.8%, personality disorder 3.6%). Lifetime MD prevalence was 24.6% (95% CI, 21.6-27.6; affective 14.9%, anxiety 15.5%, psychotic 3.4%, addiction 4.4%, personality disorder 3.6%). Female sex was associated with MD, but this appeared partially due to higher levels of neuroticism among women. MD also correlated significantly with cannabis use, family history of MD, higher social adversity, higher suicide risk, poorer physical health, poorer cognitive performance, and personality problems.

Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations.

Importance: The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. Objective: To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). Design, Setting, and Patients: This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017. Main Outcomes and Measures: Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased. Results: Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3). Conclusions and Relevance: The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability.

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals.

BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (ß = 0.12, P = 2.7 × 10-4) and with the Han/Eskin random effects method (P = 1.4 × 10-7) but not with traditional random effects (ß = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (ß = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10-8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTOConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.