Risk Factor For Major Depressive Disorder Research Articles

Attenuated frontotemporal brain activation during cognitive tasks is associated with lower succinate dehydrogenase protein levels in patients with major depressive disorder

BackgroundPrevious studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism. MethodsFifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay. ResultsActivation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD. ConclusionsMDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD. LimitationsThe sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system.

Dysfunction of neurotransmitter metabolism is associated with the severity of depression in first-diagnosed, drug-naïve depressed patients

Background & aimsBiochemical changes of neurotransmitters underlying major depressive disorder (MDD) are unknown. This study preliminarily explored the association between neurotransmitters with MDD and the possibility of objective laboratory prediction of neurotransmitter involvement in MDD. MethodsA total of 87 first-diagnosed, drug-naïve patients with depression and 50 healthy controls (HCs) were included in the cross-sectional study. The levels and turnovers of neurotransmitters (glutamine (GLN), glutamic acid (GLU), γ-2Aminobutiric acid (GABA), kainate (KA), vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid (HVA), dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA)) were determined and the confounding factors were adjusted. Then a correlation and a predictive analysis towards neurotransmitters for MDD were performed. ResultsAfter adjusting confounding factors, GLU (OR = 1.159), (GLU+ GABA)/GLN (OR = 1.217), DOPAC (OR = 1.106), DOPAC/DA (OR = 1.089) and (DOPAC+ HVA)/DA (OR = 1.026) enacted as risk factors of MDD, while KYN (OR = 0.992) was a protective factor. GABAergic and TRPergic pathways were associated with severity of depressive and anxiety symptoms in patients with depression. The predictive model for MDD (AUC = 0.775, 95%CI 0.683–0.860) consisted of KYN (OR = 0.990) and (GLU + GABA)/GLN (OR = 4.101). ConclusionsFirst-diagnosed, drug-naïve depression patients showed abnormal neurotransmitter composition. GLU, (GLU + GABA)/GLN, DOPAC, DOPAC/DA and (DOPAC + HVA)/DA were risk factors of MDD, while KYN was a protective factor. GABAergic and TRPergic pathways were correlated with MDD clinical characteristics. KYN and (GLU + GABA)/GLN may have a predictive value for MDD.

Investigating the causal effects of smoking, sleep, and BMI on major depressive disorder and bipolar disorder: a univariable and multivariable two-sample Mendelian randomization study.

Mental disorders, characterized as products of biopsychosocial interactions, have emerged as a leading contributor to the worldwide rise in overall morbidity and disability rates. Life's essentials can affect nearly every aspect of our lives, from physical to mental health. In this study, we try to identify the associations between life's essentials and mental disorders. Three assumptions of Mendelian randomization (MR) were applied to obtain the genetic instruments associated with smoking, sleep, and body mass index (BMI) in genome-wide association studies. Then, we conducted univariable MR (UVMR) and multivariable MR (MVMR) two-sample analyses to estimate the causal effects of these life's essentials on two mental disorders namely, major depressive disorder (MDD) and bipolar disorder (BD). Additionally, multiple sensitivity analyses were performed to evaluate the reliability and stability of the study results. In the MR analysis of the association of smoking, sleep, and BMI with MDD, we obtained 78, 39, and 302 genetic instruments, respectively. Smoking [odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01-1.06; p = 0.004], sleep (OR, 1.04; 95% CI, 1.02-1.06; p < 0.001), and BMI (OR, 1.01; 95% CI, 1.01-1.02; p < 0.001) were all considered as risk factors for MDD and were independent of each other (smoking: OR, 1.03, 95% CI, 1.01-1.06, p = 0.008; sleep: OR, 1.03, 95% CI, 1.01-1.05, p = 0.001; and BMI: OR, 1.01, 95% CI, 1.01-1.02, p < 0.001). Additionally, 78, 38, and 297 genetic instruments were obtained in the MR analysis of smoking, sleep, and BMI with BD, respectively. Causal associations were observed between smoking (OR, 2.46; 95% CI, 1.17-5.15; p = 0.017), sleep (OR, 2.73; 95% CI, 1.52-4.92; p < 0.001), and BD, and smoking (OR, 2.43; 95% CI, 1.69-3.16; p = 0.018) might be a mediator in the causal effects of sleep on BD. Finally, there was no inconsistency between sensitivity and causality analysis, proving that our results are convincing. The study results provide strong evidence that smoking, sleep, and BMI are causally related to MDD and BD, which need further research to clarify the underlying mechanism.

Problematic internet use and sleep quality in adolescents with major depressive disorder

ABSTRACT This study aims to compare adolescents newly diagnosed with major depressive disorder (MDD) and healthy controls in terms of problematic internet use (PIU) and sleep quality. The study sample consisted of 50 newly diagnosed MDD patients aged 12–18 years and 50 healthy controls. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) was administered to all cases by a child psychiatrist and sociodemographic data were collected. Children’s Depression Inventory (CDI), Pittsburgh Sleep Quality Index (PSQI), and Internet Addiction Test (IAT) were administered to all participants. Data of the MDD and control groups were compared using Student’s t-test or Mann-Whitney U test and the total scores of the IAT (z = −6.23, p < 0.001) and PSQI (t =–11.42, p < 0.001) scales were found to be significantly higher in MDD cases compared to the control group. The results of analysis of covariance demonstrated that there was a significant positive correlation between CDI and IAT, as well as CDI and PSQI total scores in patients with MDD. While no correlation was observed between the total scores of the IAT and PSQI scales in the MDD group, a significant positive correlation was found between the total scores of the IAT and PSQI scales in the healthy control group. Furthermore, there was a significant difference between the PSQI habitual sleep efficiency subscale score and the IAT total score (r = 0.36, p = 0.009), and the IAT responsibility (r = 0.34, p = 0.015), relationship (r = 0.36, p = 0.01), and mood subscale scores (r = 0.30, p = 0.03). A significant positive correlation was also found between the IAT duration subscale score and PSQI sleep disorder subscale score (r = 0.35, p = 0.013). In addition, binary logistic regression analysis showed that PSQI total score (B = 0.79, p < 0.001) and IAT total scores (B = 0.08, p = 0.001) could be significant predictors of MDD. The findings of this study indicate that the prevalence of PIU and poor sleep quality is higher in adolescents with newly diagnosed MDD compared to healthy controls. The results of our study indicated that the severity of depression, PIU, and sleep quality were significantly correlated in adolescents with newly diagnosed MDD, while PIU and sleep quality were correlated in adolescents without any psychiatric disorders. In addition, this study suggests that poor sleep quality and PIU may be risk factors for MDD.

Depression phenotypes in spinal cord injury and impact on post-injury healthcare utilization and cost: Analysis using a large claim database

Context/Objective Depression is the most common psychological comorbidity associated with spinal cord injury (SCI) and affects healthcare utilization and costs. This study aimed to use an International Classification of Disease (ICD) and prescription drug-based depression phenotypes to classify people with SCI, and to evaluate the prevalence of those phenotypes, associated risk factors, and healthcare utilization. Design Retrospective Observational Study Setting Marketscan Database (2000–2019) Participants Individuals with SCI were classified into six ICD-9/10, and prescription drugs defined phenotypes: Major Depressive Disorder (MDD), Other Depression (OthDep), Antidepressants for Other Psychiatric Conditions (PsychRx), Antidepressants for non-psychiatric condition (NoPsychRx), Other Non-depression Psychiatric conditions only (NonDepPsych), and No Depression (NoDep). Except for the latter, all the other groups were referred to as “depressed phenotypes”. Data were screened for 24 months pre- and 24 months post-injury depression. Interventions None Outcome Measures Healthcare utilization and payments Results There were 9,291 patients with SCI classified as follows: 16% MDD, 11% OthDep, 13% PsychRx, 13% NonPsychRx, 14% NonDepPsych, 33% NoDep. Compared with the NoDep group, the MDD group was younger (54 vs. 57 years old), predominantly female (55% vs. 42%), with Medicaid coverage (42% vs. 12%), had increased comorbidities (69% vs. 54%), had fewer traumatic injuries (51% vs. 54%) and had higher chronic 12-month pre-SCI opioid use (19% vs. 9%) (all P < 0.0001). Classification into a depressed phenotype before SCI was found to be significantly associated with depression phenotype post-SCI, as evidenced by those who experienced a negative change (37%) vs. a positive change (15%, P < 0.0001). Patients in the MDD cohort had higher healthcare utilization and associated payments at 12 and 24 months after SCI. Conclusion Increasing awareness of psychiatric history and MDD risk factors may improve identifying and managing higher-risk patients with SCI, ultimately optimizing their post-injury healthcare utilization and cost. This method of classifying depression phenotypes provides a simple and practical way to obtain this information by screening through pre-injury medical records.

National screening for anxiety and depression in Saudi Arabia 2022.

Mental health disorders, such as major depressive disorder (MDD) and generalized anxiety disorder (GAD), represent a significant public health concern in Saudi Arabia. This study aims to provide a recent mental health screening prevalence, including anxiety and depression screening in the general public and to explore the associated risk factors. A cross-sectional study was conducted, employing a phone interview survey with 6,015 participants, using a quota sampling strategy to ensure equal representation of both sexes and administrative regions. The study assessed the prevalence of MDD and GAD risk and examined demographic, socioeconomic, and lifestyle factors associated with these mental health disorders. The national prevalence of people at risk of MDD and GAD were found to be 12.7 and 12.4%, respectively. Low diagnosis and treatment rates were observed, with only 1.5 and 0.5% of participants currently diagnosed and treated for depression and anxiety, respectively. Risk factors for MDD and GAD included female sex, lower education and income levels, smoking, and waterpipe use. Protective factors included physical activity, participation in volunteering activities and the practice of daily hobbies in the last 30 days. The relatively high prevalence of MDD and GAD risk and low diagnosis and treatment rates in Saudi Arabia emphasize the need for increased mental health promotion, early detection, and treatment accessibility. The study highlights the importance of addressing modifiable risk factors and fostering protective factors through targeted interventions. Future research should focus on longitudinal associations, potential mediators and moderators, and the development of culturally appropriate and evidence-based interventions to enhance mental health outcomes in the region.

The Impact of Stressful Life Events after Bereavement: A Nationwide Cross-sectional Survey.

Bereaved family members sometimes experience distress due to stressful life events. However, the effects of this distress on depression and grief remain unclear. To clarify the degree of distress due to postbereavement stressful life events, its associated factors, especially social isolation, and its effects on major depressive disorder (MDD) and complicated grief (CG) risks among bereaved family members of patients with cancer. This cross-sectional questionnaire survey was conducted in 2018 as part of the J-HOPE4 study. We recruited 1740 bereaved family members of patients with cancer who died from July to August of 2018. We assessed distress due to postbereavement stressful life events with the Bereavement Secondary Stressor Scale, social isolation with the Lubben Social Network Scale Short-Form, and the MDD and CG risk with the Patient Health Questionnaire-9 and Brief Grief Questionnaire, respectively. Among the 913 (52.5%) respondents, 88%, 57%, 46%, 28%, and 19% experienced distress due to incidental tasks, daily life difficulties, financial problems, problems with other people, and deterioration of family relationships, respectively. More distress was associated with higher risks of MDD (odds ratio [OR]=2.5, P < 0.01) and CG (OR=2.5, P < 0.01). Social isolation and specific backgrounds were associated with more distress in response to stressful life events. Most family members experienced distress due to stressful life events, which were risk factors for MDD and CG. Assessing risk factors for maladaptation to post-bereavement life changes and enhancing readiness to adapt to them is important.

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.

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.

Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

P351. Gray Matter Volume Differences Associated With Serotonin 1A Receptor Gene DNA Methylation and Reported Childhood Abuse in Major Depressive Disorder

The serotonin 1A (5-HT1A) receptor is thought to be involved in the pathophysiology of major depressive disorder (MDD) and may mediate neurotrophic effects of serotonin. Environmental stress, including early life adversity, is a risk factor for MDD, and has been associated with epigenetic changes. We examined relationships between childhood abuse, 5-HT1A receptor promoter DNA methylation of repressor sites, and gray matter volume (GMV) in MDD. We hypothesized that more methylation would increase gene expression and serotonin transmission via these receptors and thereby GMV.

Longitudinal associations between adolescents’ individualised risk for depression and inflammation in a UK cohort study

Inflammation is associated with poor physical and mental health including major depressive disorder (MDD). Moreover, there is evidence that childhood adversity – a risk factor for MDD – becomes biologically embedded via elevated inflammation. However, the risk of developing MDD arises from multiple sources and yet there has been little investigation of the links between individuals’ constellation of MDD risk and subsequent inflammation. We therefore examined associations between individual risk for MDD calculated in early adolescence and levels of inflammation six years later. We use data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative UK birth cohort of 2,232 children followed to age 18 with 93% retention. Participants’ individual risk for developing future MDD was calculated at age 12 using a recently developed prediction model comprising multiple psychosocial factors. Plasma levels of three inflammation biomarkers were measured at age 18: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to reflect the level of systemic chronic inflammation. MDD risk scores calculated at age 12 were positively associated with levels of suPAR (but not CRP or IL-6) at age 18 after adjusting for key covariates (b = 1.70, 95% CI = 0.46 – 2.95, p = 0.007). Adolescents at high risk of MDD (risk scores ≥ 90th centile) had significantly higher mean levels of suPAR six years later than adolescents who had been identified as low risk (risk scores ≤ 10th centile) (b = 0.41, 95% CI = 0.18 – 0.64, p < 0.001). Findings support the notion that childhood psychosocial risk for MDD leads to increased levels of low-grade inflammation. If replicated in studies with repeated assessments of inflammation biomarkers throughout childhood and adolescence, these findings would support targeted interventions to reduce inflammation, as measured by suPAR, for adolescents at high risk of MDD to potentially prevent development of depression and physical health problems related to chronic inflammation.

The importance of social activity to risk of major depression in older adults.

Several social determinants of health (SDoH) have been associated with the onset of major depressive disorder (MDD). However, prior studies largely focused on individual SDoH and thus less is known about the relative importance (RI) of SDoH variables, especially in older adults. Given that risk factors for MDD may differ across the lifespan, we aimed to identify the SDoH that was most strongly related to newly diagnosed MDD in a cohort of older adults. We used self-reported health-related survey data from 41 174 older adults (50-89 years, median age = 67 years) who participated in the Mayo Clinic Biobank, and linked ICD codes for MDD in the participants' electronic health records. Participants with a history of clinically documented or self-reported MDD prior to survey completion were excluded from analysis (N = 10 938, 27%). We used Cox proportional hazards models with a gradient boosting machine approach to quantify the RI of 30 pre-selected SDoH variables on the risk of future MDD diagnosis. Following biobank enrollment, 2073 older participants were diagnosed with MDD during the follow-up period (median duration = 6.7 years). The most influential SDoH was perceived level of social activity (RI = 0.17). Lower level of social activity was associated with a higher risk of MDD [hazard ratio = 2.27 (95% CI 2.00-2.50) for highest v. lowest level]. Across a range of SDoH variables, perceived level of social activity is most strongly related to MDD in older adults. Monitoring changes in the level of social activity may help identify older adults at an increased risk of MDD.

Cognitive Impairment in Adolescent Major Depressive Disorder With Nonsuicidal Self-Injury: Evidence Based on Multi-indicator ERPs.

The lifetime prevalence of major depressive disorder (MDD) in adolescents is reported to be as high as 20%; thus, MDD constitutes a significant social and public health burden. MDD is often associated with nonsuicidal self-injury (NSSI) behavior, but the contributing factors including cognitive function have not been investigated in detail. To this end, the present study evaluated cognitive impairment and psychosocial factors in associated with MDD with NSSI behavior. Eighteen and 21 drug-naïve patients with first-episode MDD with or without NSSI (NSSI+/– group) and 24 healthy control subjects (HC) were enrolled in the study. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Adolescent Self-injury Questionnaire, Beck Scale for Suicide Ideation–Chinese Version (BSI-CV), Shame Scale for Middle School Students, Sensation Seeking Scale (SSS) and Childhood Trauma Questionnaire (CTQ) were used to assess depression-related behaviors, and event-related potentials (ERPs) were recorded as a measure of cognitive function. The latency of the N1, N2, P3a, P3b, and P50 components of ERPs at the Cz electrode point; P50 amplitude and P50 inhibition (S1/S2) showed significant differences between the 3 groups. CTQ scores also differed across three groups, and the NSSI– and NSSI+ groups showed significant differences in scores on the Shame Scale for Middle School Students. Thus, cognitive function was impaired in adolescents with MDD with NSSI behavior, which was mainly manifested as memory decline, attention and executive function deficits, and low anti-interference ability. We also found that childhood abuse, lack of social support, and a sense of shame contributed to NSSI behavior. These findings provide insight into the risk factors for MDD with NSSI behavior, which can help mental health workers more effectively diagnose and treat these patients.

Variants in the Upstream Region of the Insulin Receptor Substrate-1 Gene Is Associated with Major Depressive Disorder in the Han Chinese Population.

IntroductionMajor depressive disorder (MDD) is one of the most prevalent and disabling mental disorders, although its underlying genetic mechanism remains unknown. Insulin receptor substrate-1 (IRS-1) is one of the critical downstream molecules in the insulin resistance signaling pathway, linking depression and diabetes. Therefore, we hypothesized that IRS-1 would be a susceptible gene for MDD, and we aimed to examine the genetic association between IRS-1 and MDD.MethodsThis case-control study included 583 patients with MDD and 564 controls, and the genotypic and allelic distributions of the IRS-1 gene’s four single nucleotide polymorphisms (SNPs) were detected by TaqMan SNP genotyping technology. Of the 583 patients, 191 underwent a further detailed interview about symptom severity and family history of mental illness. The chi-square or t test was used to analyze the data, and analyses were performed using SPSS19.0 software.ResultsA haplotype in the 5ʹ-upstream region of IRS-1 consisting of rs13411764 and rs3820926 was a risk factor of MDD. Patients with a family history of mental illness were more likely to have a GG genotype in rs13411764 and a G-T haplotype containing rs13411714-rs3820926.DiscussionThe findings imply that the haplotype consisting of rs13411764 and rs3820926 in the upstream of IRS-1 is a risk factor for MDD. This haplotype could affect IRS-1 expression levels, and it is mostly inherited from parents. Thus, the presence of variants in the upstream region of IRS-1 is a risk factor of MDD, and this study could serve as a convincing reference for further studies.

The burden and risk factors for postnatal depression and depressive symptomatology among women in Kampala.

Major depressive disorder (MDD) is a major global health challenge and postnatal women may be at an increased risk for this disorder. Very few studies have tested this hypothesis in sub-Saharan Africa (SSA), so it is uncertain whether risk factors implicated elsewhere in the world are relevant in SSA. We explored prevalence and risk factors for MDD and depressive symptomatology among postnatal mothers in Kampala. Three hundred postnatal mothers at Nsambya Hospital were assessed for MDD using the DSM IV-based MINI; prevalence and risk factors were determined using frequencies and regressions, respectively. Four women (1.33%) had MDD; however, 94 (31%) had 'sub-threshold' or depressive symptomatology, with which partner violence is particularly associated. MDD is rare among postnatal women in a paying hospital in Kampala; however, the high prevalence of depressive symptomatology suggests susceptibility to MDD. Longitudinal studies should investigate this hypothesis and the susceptibility due to partner violence should guide appropriate interventions.

Prevalence of and factors associated with major depressive disorder among HIV-positive individuals in Guangdong, China.

People living with HIV may suffer from mental disorders. We aimed to explore the prevalence of and factors associated with major depressive disorder (MDD) among HIV-positive individuals in Guangdong, China, about which little is known. A cross-sectional study was conducted to recruit HIV-positive individuals from the Centers for Disease Prevention and Control of Guangzhou, Zhongshan, and Yangjiang from September 2007 to September 2008. Data were collected by questionnaires. MDD was diagnosed and assessed by two psychiatrists using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) based on the DSM-IV criteria. Multiple logistic regression analyses were conducted to explore the factors associated with MDD. The prevalences of lifetime MDD and current MDD among the 339 included participants were 22.71% (95% confidence interval [CI]: 18.25-27.17%) and 12.09% (95%CI: 8.62%-15.57%), respectively. The results of multiple logistic regression showed that patients with AIDS had a higher risk of lifetime MDD (odds ratio [OR] = 2.69, 95%CI: 1.38-5.26) and current MDD (OR = 3.51, 95%CI: 1.59-7.75) than HIV-infected individuals. Participants with more number of negative life events were more likely to have lifetime MDD (OR = 2.33, 95%CI: 1.34-4.06) and current MDD (OR = 3.77, 95%CI: 1.76-8.09) than individuals with fewer negative life events. Individuals with higher score of social support were less likely to have lifetime MDD (OR = 0.45, 95%CI: 0.26-0.80) and current MDD (OR = 0.46, 95%CI: 0.21-0.97) than individuals with less social support. The prevalence of MDD was high among HIV-positive individuals in China. AIDS diagnosis, decreased social support, and an increased number of negative life events were risk factors for MDD.

The brain-adipocyte-gut network: Linking obesity and depression subtypes.

Major depressive disorder (MDD) and obesity are dominant and inter-related health burdens. Obesity is a risk factor for MDD, and there is evidence MDD increases risk of obesity. However, description of a bidirectional relationship between obesity and MDD is misleading, as closer examination reveals distinct unidirectional relationships in MDD subtypes. MDD is frequently associated with weight loss, although obesity promotes MDD. In contrast, MDD with atypical features (MDD-AF) is characterised by subsequent weight gain and obesity. The bases of these distinct associations remain to be detailed, with conflicting findings clouding interpretation. These associations can be viewed within a systems biology framework-the psycho-immune neuroendocrine (PINE) network shared between MDD and metabolic disorders. Shared PINE subsystem perturbations may underlie increased MDD in overweight and obese people (obesity-associated depression), while obesity in MDD-AF (depression-associated obesity) involves more complex interactions between behavioural and biomolecular changes. In the former, the chronic PINE dysfunction triggering MDD is augmented by obesity-dependent dysregulation in shared networks, including inflammatory, leptin-ghrelin, neuroendocrine, and gut microbiome systems, influenced by chronic image-associated psychological stress (particularly in younger or female patients). In MDD-AF, behavioural dysregulation, including hypersensitivity to interpersonal rejection, fundamentally underpins energy imbalance (involving hyperphagia, lethargy, hypersomnia), with evolving obesity exaggerating these drivers via positive feedback (and potentially augmenting PINE disruption). In both settings, sex and age are important determinants of outcome, associated with differences in emotional versus cognitive dysregulation. A systems biology approach is recommended for further research into the pathophysiological networks underlying MDD and linking depression and obesity.

Brain-Derived Neurotrophic Factor and Major Depressive Disorder: Evidence from Meta-Analyses.

Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with the pathophysiology of major depressive disorder (MDD). In this mini review, we explored the association between BDNF and MDD using meta-analytic evidence. Our findings indicated that the Val66Met polymorphism in the BDNF gene was not associated with MDD or hippocampal volume in patients with MDD. However, plasma/serum levels of BDNF were decreased in patients with acute MDD compared with healthy controls. Both antidepressant treatment and electroconvulsive therapy increased plasma and serum levels of BDNF in patients with MDD. Val66Met polymorphism in the BDNF gene was associated with an antidepressant response in patients with MDD. Taken together, we did not detect any plausible evidence regarding Val66Met polymorphism in the BDNF gene contributing to a risk of MDD. However, peripheral BDNF levels are decreased in patients with MDD, and the polymorphisms are associated with treatment response. In conclusion, BDNF is best understood to be a biomarker for the state of MDD and its treatment response rather than a risk factor for MDD.

Polygenic Risk, Early Adverse Life Events And Depression In The Ipsych Cohort

Background Major depressive disorder (MDD) is moderately genetic, with population-based heritability estimates of 30-40% and SNP-based heritability estimates of 20-25%. However, a large proportion of risk for MDD is attributable to the environment. Early adverse life events (EALEs), such as the death of a parent, are well-established risk factors for MDD. Candidate gene studies indicate that EALEs interact with single genes to influence MDD risk. However, mounting evidence suggests that the underlying genetic architecture of MDD is polygenic. To date, only two studies have examined whether polygenic risk (PR) interacts with early adversity to predict MDD. Peyrot et al. (2014) found in the NESDA study that the effect of PR on MDD was stronger among individuals with a history of childhood trauma. Mullins et al. (2016) found the opposite: among people with moderate/severe trauma, the log odds of MDD decreased as PR increased. The goal of this study is to evaluate the extent to which EALEs interact with PR to predict MDD in the Danish iPSYCH cohort. The iPSYCH cohort contains 88,764 individuals, including 24,693 MDD cases, making this by far the largest study on the topic to date. Methods The iPSYCH cohort has a case-cohort design, containing individuals randomly sampled from the population of people born in Denmark between May 1, 1981-Dec 31, 2005, along with additional psychiatric cases identified from the Danish Central Psychiatric Research Register. DNA was extracted from dried blood spots and amplified in triplicate. Individuals were genotyped using the PSYCH chip. In this study, we will use data from controls and cases with an MDD diagnosis (ICD-10 codes F32, F33). EALEs, including death of a parent, death of a sibling, parental hospitalization, parental imprisonment, parental unemployment, parental divorce/separation, foster care and abuse, will be assessed using information from other Danish nationwide registers. EALEs will be operationalized as a weighted count variable of the number of events experienced by each individual before the age of 15. PR scores will be calculated using the PGC2 MDD results (not including the iPSYCH sample) as the training dataset (Purcell, 2009). Statistical analyses will be conducted using Cox Proportional Hazards Models, with weights to account for the case-cohort design (Self & Prentice, 1988). Results The PR scores which will be used in this study are currently being finalized. We anticipate that this process will be finished in August, 2016, which will give us over two months to conduct the analyses and prepare the results for presentation at the WCPG conference. Discussion Pending finalization of results.