Risk Of Major Depressive Disorder Research Articles

Environmental factors in offspring of parents with mood disorders and their role in parent\u2013child transmission: findings from a 14-year prospective high-risk study

BackgroundThe factors involved in the transmission of mood disorders are only partially elucidated. Aside from genes, the family environment might play a crucial role in parent–child transmission. Our goals were to (1) assess the associations of parental bipolar disorder (BPD) and Major Depressive Disorder (MDD) with individual or shared family environmental factors, including traumatic events in offspring, parental separation, family cohesion and parental attitudes; and 2) test whether these factors were mediators of the association between exposure to parental mood disorders and the onset of these disorders in offspring.MethodsThe sample stems from an ongoing family high-risk study of mood disorders conducted in the French-speaking part of Switzerland. Given the strong impact of the age of onset of parental disorders on their transmission to children, parental disorders were dichotomized according to the onset (cut-off 21 years). Probands with early-onset (n = 30) and later-onset BPD (n = 51), early-onset (n = 21) and later-onset MDD (n = 47) and controls (n = 65), along with their spouses (n = 193) and offspring (n = 388; < 18 years on study inclusion), were assessed over a mean follow-up duration of 14 years (s.d: 4.6). The environmental measures were based on reports by offspring collected before the onset of their first mood episode.ResultsOffspring of probands with later-onset BPD and offspring of probands with both early-onset and later-onset MDD reported traumatic events more frequently than comparison offspring, whereas exposure to parental separation was more frequent in all groups of high-risk offspring. Moreover, several familial environment scores including parenting attitudes differed between offspring of probands with BPD and comparison offspring. However, none of these factors were mediators of the parent–child transmission of BPD. Among the environmental factors, traumatic events were shown to be modest mediators of the transmission of early-onset MDD.ConclusionsOur data do not support the implication of the assessed environmental factors in the parent–child transmission of BPD. In contrast to BPD, traumatic events partially mediate the parent–child transmission of early-onset MDD, which has important implications for intervention and prevention. Early therapeutic efforts in offspring exposed to these events are likely to reduce their deleterious impact on the risk of subsequent MDD.

Major Depressive Disorder: Existing Hypotheses about Pathophysiological Mechanisms and New Genetic Findings.

Major depressive disorder (MDD) is a common mental disorder generally characterized by symptoms associated with mood, pleasure and effectiveness in daily life activities. MDD is ranked as a major contributor to worldwide disability. The complex pathogenesis of MDD is not yet understood, and this is a major cause of failure to develop new therapies and MDD recurrence. Here we summarize the literature on existing hypotheses about the pathophysiological mechanisms of MDD. We describe the different approaches undertaken to understand the molecular mechanism of MDD using genetic data. Hundreds of loci have now been identified by large genome-wide association studies (GWAS). We describe these studies and how they have provided information on the biological processes, cell types, tissues and druggable targets that are enriched for MDD risk genes. We detail our understanding of the genetic correlations and causal relationships between MDD and many psychiatric and non-psychiatric disorders and traits. We highlight the challenges associated with genetic studies, including the complexity of MDD genetics in diverse populations and the need for a study of rare variants and new studies of gene-environment interactions.

Protocol for the Healing After Loss (HeAL) Study: a randomised controlled trial of interpersonal psychotherapy (IPT) for major depression following perinatal loss

IntroductionThis protocol describes a study testing the efficacy of interpersonal psychotherapy (IPT) for major depressive disorder following perinatal loss (early and late fetal death and early neonatal death). Perinatal loss...

Brief CBT Interventions May Stop Depression Before It Starts

Brief CBT Interventions May Stop Depression Before It Starts

Bullying, Psychological, and Physical Trauma During Early Life Increase Risk of Major Depressive Disorder in Adulthood: A Nationwide Community Sample of Korean Adults.

BackgroundThere is an association between early life traumas and the development of depression in adults. Few studies have used nationwide population-based samples to investigate whether the type of early life trauma differentially influences the risk of developing depression.MethodsMajor depressive disorder and early life trauma were assessed using the Korean version of the Composite International Diagnostic Interview (K-CIDI) for DSM-IV psychiatric disorder and a questionnaire for early life trauma in the Korean Epidemiological Catchment Area Study in 2016. A total of 4,652 participants were included in the final analysis. This study evaluated the effect of the type and frequency of reported early life trauma on the risk of developing MDD and the association between reported early life trauma and differential symptoms of MDD.ResultsIndividuals with reported early life trauma had a 3.7-fold increased risk of MDD. The risk of MDD was associated with bullying trauma (odds ratio (OR) = 1.847, p = 0.005) after adjusting for age, gender, marriage, job, and education years. The risk of MDD was increased as the types of reported early life traumas increased.ConclusionBullying trauma during early life represents a risk factor for MDD, especially in individuals exposed to multiple traumas in early life.

Increased Risk of Major Depressive Disorder Following Tinnitus: A Population-Based Study.

Background and PurposeIn this study, we aimed to evaluate the relationship between tinnitus and a subsequent diagnosis of major depressive disorder (MDD) by studying the incidence of both entities.DesignA retrospective cohort study.MethodsData for this observational follow-up study were retrieved from the Taiwan's National Health Insurance Dataset. A total of 375,272 patients with newly diagnosed tinnitus (study group) were retrieved. The date of first diagnosis of tinnitus was assigned as their index date. Comparison patients were selected by propensity score matching (one per case, n = 375,272 controls) from the same dataset, with their index date being the date of their first health service claim in the year of diagnosis of their matched index case. We tracked each patient's claims records for 1 year from the index date to identify those who received a diagnosis of MDD. Cox proportional hazards regression was performed to calculate the MDD hazard ratio for cases vs. controls.ResultsWe found that the overall incidence rate for MDD was 0.78 (95% CI = 0.76~0.80) per 100 person-years, being 1.17 (95% CI = 1.14~1.21) among the study cohorts and 0.38 (95% CI = 0.36~0.40) among the comparison cohorts. The log-rank test revealed that the patients in the study cohort had significantly lower one-year MDD-free survival when compared to the comparison cohort (p < 0.001). Cox proportional hazards analysis showed that the patients in the study cohort had a higher hazard of developing MDD than the patients in the comparison cohort (adjusted HR = 3.08, 95% CI = 2.90~3.27).ConclusionsIn this study, we demonstrate that tinnitus is associated with an increased hazard of subsequent MDD in Taiwan.

Polygenic Risk Score Effectively Predicts Depression Onset in Alzheimer's Disease Based on Major Depressive Disorder Risk Variants.

IntroductionDepression is a common, though heterogenous, comorbidity in late-onset Alzheimer’s Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In previous work, we demonstrated shared genetic etiology between depression and LOAD. Collectively, these previous studies suggested interactions between depression and LOAD. However, the underpinning genetic heterogeneity of depression co-occurrence with LOAD, and the various genetic etiologies predisposing depression in LOAD, are largely unknown.MethodsMajor Depressive Disorder (MDD) genome-wide association study (GWAS) summary statistics were used to create polygenic risk scores (PRS). The Religious Orders Society and Rush Memory and Aging Project (ROSMAP, n = 1,708) and National Alzheimer’s Coordinating Center (NACC, n = 10,256) datasets served as discovery and validation cohorts, respectively, to assess the PRS performance in predicting depression onset in LOAD patients.ResultsThe PRS showed marginal results in standalone models for predicting depression onset in both ROSMAP (AUC = 0.540) and NACC (AUC = 0.527). Full models, with baseline age, sex, education, and APOEε4 allele count, showed improved prediction of depression onset (ROSMAP AUC: 0.606, NACC AUC: 0.581). In time-to-event analysis, standalone PRS models showed significant effects in ROSMAP (P = 0.0051), but not in NACC cohort. Full models showed significant performance in predicting depression in LOAD for both datasets (P < 0.001 for all).ConclusionThis study provided new insights into the genetic factors contributing to depression onset in LOAD and advanced our knowledge of the genetics underlying the heterogeneity of depression in LOAD. The developed PRS accurately predicted LOAD patients with depressive symptoms, thus, has clinical implications including, diagnosis of LOAD patients at high-risk to develop depression for early anti-depressant treatment.

Association between fasting blood glucose and thyroid stimulating hormones and suicidal tendency and disease severity in patients with major depressive disorder

Thyroid dysfunction and diabetes are reported to be associated with depression. However, their role in the suicide risk in patients with major depressive disorder (MDD) is unclear. The purpose of this study was to investigate and compare thyroid dysfunction and diabetes between suicide attempters and non-suicide attempters in a large sample of first-episode drug-naïve MDD patients. A descriptive study was conducted on 1279 Chinese outpatients with a diagnosis of first-episode MDD. Their socio-demographic information, blood levels of thyroid hormones, glucose, lipids and body mass index (BMI) parameters were collected. The positive subscales of the positive and negative syndrome scale (PANSS), Hamilton anxiety rating scale (HAMA), Hamilton depression rating scale (HAMD) were measured for psychotic, anxiety and depressive symptoms. Our results showed that compared with non-suicide attempters (p < 0.01), suicide attempters had statistically higher scores on HAMD, HAMA and PANSS psychotic symptoms, as well as higher thyroid stimulating hormone (TSH) serum levels, glucose, anti-thyroglobulin (A-TG), anti-thyroid peroxidase (A-TPO), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), systolic blood pressure, and diastolic blood pressure (all with p < 0.001). These results revealed that TSH, A-TG, A-TPO, TC, TG, and LDL-C may be promising biomarkers of suicide risk in MDD, implying the importance of regular assessment of blood glucose level and thyroid function parameters for suicide prevention, along with possible treatment for impaired thyroid function and diabetes for the suicide intervention in MDD patients. Such patients with abnormal blood sugar and TSH must undergo thorough screening for suicidal ideation.

Assessing the role of adolescent hormonal contraceptive use on risk for depression: a 3-year longitudinal study protocol

BackgroundThe incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females’ risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning.MethodsUsing a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be assessed at three time points: once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels.DiscussionIn this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.

Assessing the Evidence for Causal Associations Between Body Mass Index, C-Reactive Protein, Depression, and Reported Trauma Using Mendelian Randomization

BackgroundTraumatic experiences are described as the strongest predictors of major depressive disorder (MDD), with inflammation potentially mediating the association between trauma and symptom onset. However, several studies indicate that body mass index (BMI) exerts a large confounding effect on both inflammation and MDD. MethodsFirst, we sought to replicate previously reported associations between these traits in a large subset of the UK Biobank, using regression models with C-reactive protein (CRP) and MDD and as the outcome variables in 113,481 and 30,137 individuals, respectively. Second, we ran bidirectional Mendelian randomization analyses between these traits to establish a potential causal framework between BMI, MDD, reported childhood trauma, and inflammation. ResultsOur phenotypic analyses revealed no association between CRP and MDD but did suggest a strong effect of BMI and reported trauma on both CRP (BMI: β = 0.43, 95% CI = 0.43–0.43, p ≤ .001; childhood trauma: β = 0.02, 95% CI = 0.00–0.03, p = .006) and MDD (BMI: odds ratio [OR] = 1.16, 95% CI = 1.14–1.19, p ≤ .001; childhood trauma: OR = 1.99, 95% CI = 1.88–2.11, p ≤ .001). Our Mendelian randomization analyses confirmed a lack of causal relationship between CRP and MDD but showed evidence consistent with a strong causal influence of higher BMI on increased CRP (β = 0.37, 95% CI = 0.36–0.39, p ≤ .001) and a bidirectional influence between reported trauma and MDD (OR trauma-MDD = 1.75, 95% CI = 1.49–2.07, p ≤ .001; OR MDD-trauma = 1.22, 95% CI = 1.18–1.27, p ≤ .001). ConclusionsOur findings highlight the importance of controlling for both BMI and trauma when studying MDD in the context of inflammation. They also suggest that the experience of traumatic events can increase the risk for MDD and that MDD can increase the experience of traumatic events.

Community-Level Social Support Infrastructure and Adult Onset of Major Depressive Disorder in a South Asian Postconflict Setting

Individual-level social support protects against major depressive disorder (MDD) among adults exposed to trauma. Little is known about the consequences of community-level interventions in the general population. To determine the potential consequences of neighborhood social infrastructure on incident MDD in a high-risk general population. This longitudinal, multilevel study estimated associations between a neighborhood-level program in a case-control design and subsequent individual outcomes across 10 years (2006-2015) in a cohort of young adults. Exogenously placed social programs simulate natural experiment conditions in a high-poverty population experiencing armed conflict (1998-2006). The western Chitwan valley in Nepal has a general population at high risk of MDD, with neighborhoods exposed to interventions to improve social support. From a random sample (response rate 93%) selected to represent the general population in 2016, participants aged 25 to 34 years in 2006 were studied. These individuals resided within 149 neighborhoods that varied in their availability of active social support programs. The analyses were conducted between October 2020 and November 2021. The Small Farmers Development Program (SFDP) uses shared, joint liability financial credit among neighbors to build social capital and cohesion within neighborhoods. Onset of DSM-IV MDD after the conflict, assessed by the Nepal-specific, clinically validated World Mental Health Composite International Diagnostic Interview with a life history calendar. The hypothesis tested was that exposure to SFDP reduced adult onset of MDD. Of the 1917 survey participants, 886 (46.2%) were women, and 856 (44.7%) were of Brahmin or Chhetri ethnicity. Of the 149 neighborhoods, 21 had an active SFDP group, and 156 of 1917 (8.1%) participants experienced MDD between 2006 and 2015. Discrete-time hazard models showed participants living in neighborhoods with an SFDP experienced incident MDD at nearly half the rate as others (odds ratio = 0.55; 95% CI, 0.30-1.02; P = .06). A multivariate, multilevel matching analysis showed the incidence of MDD among adults living in neighborhoods with an SFDP was 19 of 256 (7.4%), compared with 33 of 256 (12.9%) in the matched sample with no SFDP (z = 2.05; P = .04). Living in a neighborhood with community-level social support infrastructure was associated with reduced subsequent rates of adult-onset MDD, even in this high-risk population. Investments in such infrastructure may reduce population-level MDD, supporting clinical focus on potentially unpreventable cases.

Neural correlates of reward processing distinguish healthy youth at familial risk for bipolar disorder from youth at familial risk for major depressive disorder

Youth at familial risk for bipolar disorder (BD-risk) and major depressive disorder (MDD-risk) have aberrant reward processing, a core feature of these mood disorders. Whether BD risk differentiates from MDD risk in reward processing merits further study. We compared neural activation and connectivity during anticipation and outcome of monetary gain and loss during fMRI using the Monetary Incentive Delay (MID) Task among BD-risk (n = 40), MDD-risk (n = 41), and healthy comparison youth (HC) (n = 45), in the absence of any lifetime or current history of psychopathology [mean age 13.09 ± 2.58, 56.3% female]. Participants completed the MID task at baseline and were followed for behavioral and clinical outcomes over 4.37 ± 2.29 years. Region-of-interest (ROI) analyses conducted using anatomically defined thalamus, ventrolateral prefrontal cortex, nucleus accumbens, and putamen seeds showed that relative to MDD-risk and HC, BD-risk had decreased activation of the thalamus during anticipation of monetary gain [F(2,118) = 4.64, p = 0.01 (FDR-corrected p = 0.04)]. Psychophysiological interaction analyses revealed that BD-risk had less connectivity between the thalamus and left middle frontal gyrus (Z > 3.1, p < 0.001) and left-superior temporal gyrus (Z > 3.1, p < 0.05) compared with MDD-risk. Voxelwise, BD-risk had decreased activation in the cerebellum during anticipation and outcome of monetary gain relative to MDD-risk and HC (Z > 3.1, p < 0.001; Z > 3.1, p < 0.01). In BD-risk, decreased thalamic connectivity was associated with increased impulsivity at baseline and reduced prosocial behavior at follow-up. Reduced thalamic activation and connectivity during reward processing may distinguish familial risk for BD from familial risk for MDD and represent early markers of vulnerability that may herald social dysfunction later in adolescence.

Risk of major depressive disorder in adolescent and young adult cancer patients in Japan.

ObjectiveTo estimate the risk of major depressive disorder (MDD) in adolescent and young adult (AYA) patients with cancer in Japan and identify risk factors for MDD among these patients.MethodsThis was a matched cohort study using a large claims database in Japan. Included patients were aged 15–39 years, newly diagnosed with cancer during 2012–2017 and assessable for a follow‐up period of 12 months. Kaplan–Meier estimates and Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for MDD in the AYA patients with cancer versus age‐, sex‐ and working status‐matched cancer‐free controls. A subgroups analysis of the AYA patients with cancer was performed to explore MDD risk factors.ResultsA total of 3559 AYA patients with cancer and 35,590 matched controls were included in the analysis. Adolescent and young adult patients with cancer had a three‐fold higher risk for MDD compared with cancer‐free controls (HR, 3.12; 95% CI, 2.64–3.70). Among cancer categories with >100 patients, patients with multiple cancer categories, including those with metastatic cancer (HR, 6.73, 95% CI, 3.65–12.40) and leukemia (HR, 6.30; 95% CI, 3.75–10.58), had the greatest MDD risk versus matched controls. Patients who received inpatient chemotherapy as initial treatment had a higher risk for MDD than patients without chemotherapy (HR, 0.43; 95% CI, 0.30–0.62).ConclusionsAdolescent and young adult patients in Japan with cancer are at high risk for MDD. Particularly, those with multiple cancer categories, leukemia, and those who receive aggressive anticancer treatments should be monitored closely for symptoms of MDD.

Periaqueductal gray is required for controlling chronic stress-induced depression-like behavior

BackgroundEnduring exposure to psychological stress is associated with an elevated risk of major depressive disorder (MDD). There is an enormous need to investigate the unexplored mechanisms of MDD. We examined whether pain-free stress alters synaptic transmission, causing depression-like behaviors in the ventrolateral periaqueductal gray (vlPAG), a brain stem nucleus that controls stress-related depression-like behavior. MethodsIn the current study, we studied neuronal changes in the vlPAG and behavioral transforms using electrophysiological recordings, behavioral tests, and pharmacological approaches. ResultsWe found that chronic restraint stress (CRS) diminished glutamatergic transmission in the vlPAG, leading to maladaptive behavioral despair and anhedonia in mice demonstrated by the forced swimming test (FST), tail suspension test (TST) and female urine sniffing test (FUST). Moreover, CRS increased behavioral hypersensitivity shown by the von Frey test. Bath perfusion with the rapid-acting antidepressant (2R,6R)-hydroxynorketamine (HNK) increased both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in vlPAG neurons in the CRS and control groups. Functionally, (2R,6R)-HNK directly enhanced the action potential firing rate in vlPAG neurons. Behaviorally, intravlPAG microinjection of (2R,6R)-HNK alleviated chronic restraint stress-induced depression-like behaviors and behavioral hypersensitivity. ConclusionsThese results demonstrate that psychological stress-elicited depression-like behavior is related to a remarkable decrease in glutamatergic transmission in the vlPAG. The maladaptive behaviors are attributed to hypoactivity of glutamatergic neurons in the vlPAG, and direct enhancement of glutamatergic neuronal activity in the vlPAG rescues depression-like behaviors. The present results prove that vlPAG is critical for controlling stress-induced depression-like behaviors through alteration of glutamatergic transmission.

Perinatal depression is associated with a higher polygenic risk for major depressive disorder than non-perinatal depression.

Distinctions between major depressive disorder (MDD) and perinatal depression (PND) reflect varying views of PND, from a unique etiological subtype of MDD to an MDD episode that happens to coincide with childbirth. This case-control study investigated genetic differences between PND and MDD outside the perinatal period (non-perinatal depression or NPD). We conducted a genome-wide association studyusing PND cases (Edinburgh Postnatal Depression Scale score ≥ 13) from the Australian Genetics of Depression Study2018 data (n = 3804) and screened controls (n = 6134). Results of gene-set enrichment analysis were compared with those of women with non-PND. For six psychiatric disorders/traits, genetic correlations with PND were evaluated, and logistic regression analysis reported polygenic score (PGS) association with both PND and NPD. Genes differentially expressed in ovarian tissue were significantly enriched (stdBeta = 0.07, p = 3.3e-04), but were not found to be associated with NPD. The genetic correlation between PND and MDD was 0.93 (SE = 0.07; p = 3.5e-38). Compared with controls, PGS for MDD are higher for PND cases (odds ratio [OR] = 1.8, confidence interval [CI] = [1.7-1.8], p = 9.5e-140) than for NPD cases (OR = 1.6, CI = [1.5-1.7], p = 1.2e-49). Highest risk is for those reporting both antenatal and postnatal depression, irrespective of prior MDD history. PND has a high genetic overlap with MDD, but points of distinction focus on differential expression in ovarian tissue and higher MDD PGS, particularly for women experiencing both antenatal and postpartum PND.

Gene-gene interaction and new onset of major depressive disorder: Findings from a Chinese freshmen nested case-control study

BackgroundThe gene-gene interaction is known to be the genetic cause of major depressive disorder (MDD). Several genes have been found to be related to MDD. The objectives of this study were to verify the susceptibility genes of MDD in a sample of university students in China, and to investigate possible gene-gene interactions in relation to the risk of MDD. Methods7,627 Chinese Han freshmen were enrolled at baseline survey in 2018. After a 2-year follow-up, 170 new onset MDD cases and 680 controls with DNA samples reserved were sequenced and genotyped for 4 selected Single Nucleotide Polymorphisms (SNPs) in a nested case-control study (ratio of 1:4). Chi-square test was used to identify the relationships between SNPs and risk of MDD. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interactions. ResultsThe 2-year incidence of MDD in Chinese college students was 3.75% (95% CI: 3.24%, 4.34%). There was no statistical difference in MDD incidences between males (3.74%, 95% CI: 3.12%, 4.49%) and females (3.77%, 95% CI: 2.97%, 4.78%) (p>0.05). TMEM161B (rs768705) was positively associated with new onset MDD (χ2 = 0.75, p = 0.023). The AG genotype of rs768705 was significant (OR=1.640, 95%CI:1.414–2.358). The gene-gene interaction between TMEM161B (rs768705) and LHPP (rs35936514) was statistically significant in this nested case-control study (p = 0.011). The CV consistency was 9/10 and the testing accuracy was 0.5274. LimitationsThe results could not be inferred to other ethnics. ConclusionsThis study provided evidence that combined rs768705 (TMEM161B) and rs35936514 (LHPP) may modulate the risk of MDD.

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.

Race and nonrace-specific attributions of discrimination: Implications for major depressive disorder among African American, Black Caribbean, and White adults.

The discrimination and health literature has not clearly resolved whether race-based experiences with discrimination are meaningfully distinct from other forms of unfair treatment or whether race-based experiences affect racial and ethnic minorities differently than non-Hispanic Whites. This study compared the effects of racial and nonrace-specific discrimination on lifetime risk for major depressive disorder (MDD) using data from the National Survey of American Life (NSAL), a nationally representative sample of African Americans, Caribbean Blacks, and non-Hispanic Whites (N = 6,082). Discrimination was defined in two ways: (a) nonrace-specific (any experience of discrimination regardless of the attribution) and (b) racial (discrimination attributed to a race-related reason such as race or skin color), which allowed for an assessment of any unique effects of racial discrimination on MDD risk for each ethnic group. Nonrace-specific discrimination was associated with increased MDD risk among both African Americans and non-Hispanic Whites. However, race-specific discrimination was associated with increased MDD risk for African Americans and Black Caribbeans, but not non-Hispanic Whites. These findings suggest that nonrace-specific discrimination measures-used commonly in the existing literature-may obscure unique associations between racial discrimination and depression; race-related discrimination may have uniquely detrimental consequences for MDD risk among Black people (e.g., African Americans and Black Caribbeans). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sleep disturbance and psychiatric disorders: a bidirectional Mendelian randomisation study.

Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear. To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS). The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22-1.45; p = 5.03 × 10-11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25-1.37; p = 6.88 × 10-31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23-1.40; p = 1.42 × 10-16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03-1.10, p = 7.85 × 10-4 for PTSD; OR = 1.37, 95% CI 1.14-1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed. Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.

Understanding Sleepiness and Fatigue in Cabin Crew Using COVID-19 to Dissociate Causative Factors.

OBJECTIVES: Airline cabin crew experience high levels of fatigue and sleepiness. Whether these are solely related to their work schedules/jetlag or are in part related to individual factors is unknown. The COVID-19 pandemic has significantly disrupted the aviation industry and many cabin crew have been grounded. This provides a unique opportunity to assess the causes of fatigue and sleepiness in this population.METHODS: An online anonymous survey was distributed in April-June 2020 to cabin crew who were 1) flying, 2) grounded but doing alternative work, and 3) grounded, not working, or unemployed. The survey measured fatigue, sleepiness, and mental health. It also screened their risk for insomnia, depression, and shift work disorder and assessed drug and caffeine use.RESULTS: Collected were 409 valid responses: 45 currently flying; 35 grounded but doing alternate work; and 329 not working. On average, all three groups experienced normal levels of fatigue and sleepiness. The risk for major depressive disorder was 27.4%, with 59.5% of individuals reporting abnormal levels of anxiety. Caffeine intake and the use of drugs and alcohol to facilitate sleep were common, although not different between those currently flying vs. grounded.CONCLUSIONS: With reduced workloads or not flying, cabin crew reported lowered fatigue and sleepiness compared to prepandemic findings, along with reduced risk for major depressive disorder. However, a high occurrence of negative emotional states were reported, potentially related to the uncertainty surrounding the pandemic. This study suggests fatigue and sleepiness is primarily related to airline operational rather than personal variables.Wen CC-Y, Nicholas CL, Howard ME, Trinder J, Jordan AS. Understanding sleepiness and fatigue in cabin crew using COVID-19 to dissociate causative factors. Aerosp Med Hum Perform. 2022; 93(1):50-53.