Major Depressive Disorder Status Research Articles

Polygenic prediction of major depressive disorder and related traits in African ancestries UK Biobank participants.

Genome-Wide Association Studies (GWAS) over-represent European ancestries, neglecting all other ancestry groups and low-income nations. Consequently, polygenic risk scores (PRS) more accurately predict complex traits in Europeans than African Ancestries groups. Very few studies have looked at the transferability of European-derived PRS for behavioural and mental health phenotypes to Africans. We assessed the comparative accuracy of depression PRS trained on European and African Ancestries GWAS studies to predict major depressive disorder (MDD) and related traits in African ancestry participants from the UK Biobank. UK Biobank participants were selected based on Principal component analysis clustering with an African genetic similarity reference population, MDD was assessed with the Composite International Diagnostic Interview (CIDI). PRS were computed using PRSice2 software using either European or African Ancestries GWAS summary statistics. PRS trained on European ancestry samples (246,363 cases) predicted case control status in Africans of the UK Biobank with similar accuracies (R2 = 2%, β = 0.32, empirical p-value = 0.002) to PRS trained on far much smaller samples of African Ancestries participants from 23andMe, Inc. (5045 cases, R² = 1.8%, β = 0.28, empirical p-value = 0.008). This suggests that prediction of MDD status from Africans to Africans had greater efficiency relative to discovery sample size than prediction of MDD from Europeans to Africans. Prediction of MDD status in African UK Biobank participants using GWAS findings of likely causal risk factors from European ancestries was non-significant. GWAS of MDD in European ancestries are inefficient for improving polygenic prediction in African samples; urgent MDD studies in Africa are needed.

The metabolome-wide signature of major depressive disorder.

Major Depressive Disorder (MDD) is a common, frequently chronic condition characterized by substantial molecular alterations and pathway dysregulations. Single metabolite and targeted metabolomics platforms have revealed several metabolic alterations in depression, including energy metabolism, neurotransmission, and lipid metabolism. More comprehensive coverage of the metabolome is needed to further specify metabolic dysregulations in depression and reveal previously untargeted mechanisms. Here, we measured 820 metabolites using the metabolome-wide Metabolon platform in 2770 subjects from a large Dutch clinical cohort with extensive clinical phenotyping (1101 current MDD, 868 remitted MDD, 801 healthy controls) at baseline, which were repeated in 1805 subjects at 6-year follow up (327 current MDD, 1045 remitted MDD, 433 healthy controls). MDD diagnosis was based on DSM-IV psychiatric interviews. Depression severity was measured with the Inventory of Depressive Symptomatology Self-report. Associations between metabolites and MDD status and depression severity were assessed at baseline and at 6-year follow-up. At baseline, 139 and 126 metabolites were associated with current MDD status and depression severity, respectively, with 79 overlapping metabolites. Adding body mass index and lipid-lowering medication to the models changed results only marginally. Among the overlapping metabolites, 34 were confirmed in internal replication analyses using 6-year follow-up data. Downregulated metabolites were enriched with long-chain monounsaturated (P = 6.7e-07) and saturated (P = 3.2e-05) fatty acids; upregulated metabolites were enriched with lysophospholipids (P = 3.4e-4). Mendelian randomization analyses using genetic instruments for metabolites (N = 14,000) and MDD (N = 800,000) showed that genetically predicted higher levels of the lysophospholipid 1-linoleoyl-GPE (18:2) were associated with greater risk of depression. The identified metabolome-wide profile of depression indicated altered lipid metabolism with downregulation of long-chain fatty acids and upregulation of lysophospholipids, for which causal involvement was suggested using genetic tools. This metabolomics signature offers a window on depression pathophysiology and a potential access point for the development of novel therapeutic approaches.

Multimodal digital assessment of depression with actigraphy and app in Hong Kong Chinese

There is an emerging potential for digital assessment of depression. In this study, Chinese patients with major depressive disorder (MDD) and controls underwent a week of multimodal measurement including actigraphy and app-based measures (D-MOMO) to record rest-activity, facial expression, voice, and mood states. Seven machine-learning models (Random Forest [RF], Logistic regression [LR], Support vector machine [SVM], K-Nearest Neighbors [KNN], Decision tree [DT], Naive Bayes [NB], and Artificial Neural Networks [ANN]) with leave-one-out cross-validation were applied to detect lifetime diagnosis of MDD and non-remission status. Eighty MDD subjects and 76 age- and sex-matched controls completed the actigraphy, while 61 MDD subjects and 47 controls completed the app-based assessment. MDD subjects had lower mobile time (P = 0.006), later sleep midpoint (P = 0.047) and Acrophase (P = 0.024) than controls. For app measurement, MDD subjects had more frequent brow lowering (P = 0.023), less lip corner pulling (P = 0.007), higher pause variability (P = 0.046), more frequent self-reference (P = 0.024) and negative emotion words (P = 0.002), lower articulation rate (P < 0.001) and happiness level (P < 0.001) than controls. With the fusion of all digital modalities, the predictive performance (F1-score) of ANN for a lifetime diagnosis of MDD was 0.81 and 0.70 for non-remission status when combined with the HADS-D item score, respectively. Multimodal digital measurement is a feasible diagnostic tool for depression in Chinese. A combination of multimodal measurement and machine-learning approach has enhanced the performance of digital markers in phenotyping and diagnosis of MDD.

The Association of HHV-6 and the TNF-α (-308G/A) Promotor with Major Depressive Disorder Patients and Healthy Controls in Thailand.

Major depressive disorder (MDD) is a silent global health problem that can lead to suicide. MDD development is suggested to result from numerous risk factors, including genetic factors. A precise tool for MDD diagnosis is currently not available. Recently, inflammatory processes have been identified as being strongly involved in MDD development and the reactivation of human herpesvirus type 6 (HHV-6), upregulating cytokines such as TNF-α, which are associated with MDD. Therefore, this study aimed to determine the association of HHV-6 with genetic factors, especially TNF-α mutation, in MDD patients and their relatives compared to healthy controls. The Patient Health Questionnaire (PHQ-9) was used to evaluate MDD status, and 471 oral buccal samples were investigated for HHV-6 infection and viral copy number by qPCR. TNF-α (-308G/A) gene mutation and the cytokines TNF-α, IL-6, and IL-10 were analyzed by high-resolution melting (HRM) analysis and enzyme-linked immunosorbent assay (ELISA). Whole-exome sequencing of buccal samples was performed to analyze for genetic factors. The results showed significantly higher HHV-6 positivities and viral loads in MDD patients (15/59 (25.67%) and 14,473 ± 16,948 copies/µL DNA) and their relatives (blood relatives 17/36 (47.22%) and 8146 ± 5656 copies/µL DNA); non-blood relatives 7/16 (43.75%) and 20,721 ± 12,458 copies/µL DNA) compared to the healthy population (51/360 (14.17%) and 6303 ± 5791 copies/µL DNA). The TNF-α (-308G/A) mutation showed no significant difference. Surprisingly, 12/26 (46.15%) participants with the TNF-α (-308G/A) mutation showed HHV-6 positivities at higher rates than those with wild-type TNF-α (-308G) (70/267 (26.22%)). HHV-6-positive participants with TNF-α (-308G/A) showed higher levels of TNF-α, IL-6, and IL-10 than those of negative control. Exome analysis revealed that common mutations in immune genes were associated with depression. Therefore, this study unveiled the novel association of inflammatory gene TNF-α (-308G/A) mutations with HHV-6 reactivation, which could represent a combined risk factor for MDD. This result could induce further research on MDD development and clinical applications.

The Burden of Attention-Deficit/Hyperactivity Disorder Traits in Adult Patients with Major Depressive Disorder in Japan.

Symptoms of attention-deficit/hyperactivity disorder (ADHD) often overlap with and are hidden by those of mood disorders, including major depressive disorder (MDD), resulting in adult ADHD patients being misdiagnosed as MDD. This study aims to examine if diagnosed MDD patients are more likely to exhibit ADHD traits and if the presence of ADHD traits increases the humanistic burden, including the impairment of health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and health-care resource utilization (HRU), on MDD patients in Japan. This study utilized existing National Health and Wellness Survey (NHWS) data. The 2016 Japan NHWS is an internet-based survey comprising a total of 39,000 respondents, including those with MDD and/or ADHD. A randomly selected subset of the respondents responded to the Japanese-version Adult ADHD self-report scale (ASRS-v1.1; ASRS-J) symptom checklist. Respondents were considered ASRS-J-positive if the total score was ≥36. The HRQoL, WPAI, and HRU were assessed. Among MDD patients (n = 267), 19.9% were screened ASRS-J-positive, while 4.0% of non-MDD respondents (n = 8885) were ASRS-J-positive. There was a significant association between MDD status and ASRS-J status (crude odds-ratio [OR]: 5.9) as well as between MDD status and ADHD-diagnosis status (crude OR: 22.6). MDD patients who were ASRS-J positive experienced significantly lower HRQoL and higher WPAI than those who were ASRS-J negative. Limitations of this study include potential recall bias owing to the self-report nature of the survey and lack of objective confirmation of MDD diagnosis through review of medical records. This study demonstrated a significant association between MDD status and exhibiting ADHD traits. Adult MDD patients screened ASRS-J-positive experienced significantly higher humanistic burden than patients screened ASRS-J-negative. Our results emphasize the importance of ensuring appropriate screening of ADHD and looking out for potentially hidden ADHD symptoms when diagnosing and treating MDD in adulthood.

Stability of the Subtypes of Major Depressive Disorder in Older Adults and the Influence of Mild Cognitive Impairment on the Stability

ObjectivesTo assess 1) the longitudinal stability of the atypical, melancholic, combined atypical-melancholic and the unspecified subtypes of major depressive disorder (MDD) according to the diagnostic and statistical manual of mental disorders (DSM –IV) specifiers in older adults, and 2) the effect of mild cognitive impairment (MCI) on the stability of these subtypes. DesignProspective cohort study with a 5.1 year-follow-up. SettingPopulation-based cohort from Lausanne, Switzerland. ParticipantsA total of 1,888 participants (mean age: 61.7 years, women: 69.2%) with at least two psychiatric evaluations, one after the age of 65 years. MeasurementsSemistructured diagnostic interview to assess lifetime and 12-month DSM-IV Axis-1 disorders at each investigation and neuro-cognitive tests to identify MCI in participants aged 65 years and over. Associations between lifetime MDD status before and 12-month depression status after the follow-up were assessed using multinomial logistic regression. The effect of MCI on these associations was assessed by testing interactions between MDD subtypes and MCI status. Results1) Associations between depression status before and after the follow-up were observed for atypical (adjusted OR [95% CI] = 7.99 [3.13; 20.44]), combined (5.73 [1.50; 21.90]) and unspecified (2.14 [1.15; 3.98]), but not melancholic MDD (3.36 [0.89; 12.69]). However, there was a certain degree of overlap across the subtypes, particularly between melancholic MDD and the other subtypes. 2) No significant interactions were found between MCI and lifetime MDD subtypes regarding depression status after follow-up. ConclusionThe strong stability of the atypical subtype in particular highlights the need for identifying this subtype in clinical and research settings, given its well-documented links to inflammatory and metabolic markers.

The role of educational attainment and brain morphology in major depressive disorder: Findings from the ENIGMA major depressive disorder consortium.

Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential susceptibility marker, and in the context of low educational attainment, predict MDD. We tested this moderation model in a large multisite sample of 1958 adults with MDD and 2921 controls (aged 18 to 86) from the ENIGMA MDD working group. Using generalized linear mixed models and within-sample split-half replication, we tested whether brain structure interacted with educational attainment to predict MDD status. Analyses revealed that cortical thickness in a number of occipital, parietal, and frontal regions significantly interacted with education to predict MDD. For the majority of regions, models suggested a differential susceptibility effect, whereby thicker cortex was more likely to predict MDD in individuals with low educational attainment, but less likely to predict MDD in individuals with high educational attainment. Findings suggest that greater thickness of brain regions subserving visuomotor and social-cognitive functions confers susceptibility to MDD, dependent on level of educational attainment. Longitudinal work, however, is ultimately needed to establish whether cortical thickness represents a preexisting susceptibility marker. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Increased inflammation predicts nine-year change in major depressive disorder diagnostic status.

Cytokine theory of depression proposes that increased baseline inflammatory activity may accumulate over time and lead to future major depressive disorder (MDD). However, most research conducted on this topic has been cross-sectional and examined between- (vs. within-) persons and symptom severity (vs. diagnosis). Therefore, we tested if elevated inflammatory activity at Time 1 (T1) would predict future within-person 9-year change in MDD diagnosis. Community-dwelling adults (n = 945) participated in the Midlife Development in the United States (MIDUS) study. T1 and Time 2 (T2) MDD status was assessed using the Composite International Diagnostic Interview-Short Form, and markers of inflammatory activity at T1 were measured (e.g., levels of serum interleukin-6 [IL-6], C-reactive protein [CRP], fibrinogen). Latent change score modeling was conducted. Higher T1 IL-6, CRP, and fibrinogen levels of inflammatory activity predicted T1-T2 development/relapse of MDD within persons. This effect occurred more strongly among women (vs. men; d = .149 vs. .042), younger (vs. older) adults (d = .137 vs. .119), persons with more (vs. less) chronic health issues (d = .133 vs. .065), low- (vs. middle- or high-) income earners (d = .161 vs. .050), and persons with more (vs. less) frequent childhood trauma (d = .156 vs. .017). Findings aligned with expanded cytokine theories, which posit that the impact of increased T1 inflammatory activity on future change in MDD status will be larger for subgroups vulnerable to increased stress exposure. Cognitive-behavioral or pharmacological approaches to reduce markers of inflammatory activity may prevent development/relapse of MDD. General Scientific Summary: Increased C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) levels predicted 9-year major depressive disorder (MDD) diagnostic status change more strongly in younger than older adults, women but not men, those with low (vs. high) income, as well as persons with high (vs. low) childhood trauma frequency and number of chronic illnesses. Findings aligned with expanded cytokine theories (e.g., social signal transduction theory of depression), which posit that markers of inflammatory activity predict future change in MDD status especially for populations vulnerable to heightened, chronic, and long-term exposure to environmental stressors. Continued efforts to empirically test expanded cytokine theories of depression may improve delineation of patterns of health disparities and facilitate effective measures to prevent the onset or recurrence of MDD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Elucidating Age and Sex-Dependent Association Between Frontal EEG Asymmetry and Depression: An Application of Multiple Imputation in Functional Regression

Frontal power asymmetry (FA), a measure of brain function derived from electroencephalography, is a potential biomarker for major depressive disorder (MDD). Though FA is functional in nature, it is typically reduced to a scalar value prior to analysis, possibly obscuring its relationship with MDD and leading to a number of studies that have provided contradictory results. To overcome this issue, we sought to fit a functional regression model to characterize the association between FA and MDD status, adjusting for age, sex, cognitive ability, and handedness using data from a large clinical study that included both MDD and healthy control (HC) subjects. Since nearly 40% of the observations are missing data on either FA or cognitive ability, we propose an extension of multiple imputation (MI) by chained equations that allows for the imputation of both scalar and functional data. We also propose an extension of Rubin’s Rules for conducting valid inference in this setting. The proposed methods are evaluated in a simulation and applied to our FA data. For our FA data, a pooled analysis from the imputed datasets yielded similar results to those of the complete case analysis. We found that, among young females, HCs tended to have higher FA over the θ, α, and β frequency bands, but that the difference between HC and MDD subjects diminishes and ultimately reverses with age. For males, HCs tended to have higher FA in the β frequency band, regardless of age. Young male HCs had higher FA in the θ and α bands, but this difference diminishes with increasing age in the α band and ultimately reverses with increasing age in the θ band. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.

PMH31 Universal Screening for Suicidal Thoughts and Behaviors in a Large Healthcare System's Hospital and Emergency Departments

The Joint Commission recently revised its National Patient Safety Goal requirements to include standardizing suicide screening. Sutter Health launched system-wide standardized use of the Columbia Suicide Severity Rating Scale (C-SSRS) in acute care facilities in July 2019. Describe and compare characteristics of adult patients screening positive for suicidal thoughts or behaviors (STB) including those with major depressive disorder (MDD). Electronic health record-based observational cohort study describing and comparing sociodemographic and clinical characteristics of adult patients screening positive for STB (7/1/2019-10/4/2020), including those with MDD. MDD+STB were compared to those with STB without MDD (STB-MDD) and on risk categories (no risk v any risk). Wilcoxon rank-sum tests for continuous variables and χ2 tests for categorical variables were used. Results reported are statistically significant at 0.05. 410,302/478,143 (85.8%) of adults were screened by C-SSRS, 8,416 (2.05%) had STB, 914 (10.9%) had MDD+STB, 7,502 (89.1%) had STB without MDD. Of those with STB, 3,278 (38.9%) were low risk, 1,314 (15.6%) moderate risk, and 3,824 (45.4%) high risk. Any risk vs no risk: males (46.6% v 42.3%), White (55.5% v 47.9%), mean age 41.6 v 50.3 years, homeless in last 12 months (12.0% v 2.5%), index encounter Psych unit (10.3% v 0.2%), mental health diagnoses (22.2% v 4.9%), MDD (10.9% v 1%). MDD+STB patients vs MDD-STB: mean age 38.8 v 41.9 years, female (58.6% v 52.8%), Asian (9.7% v 6.6%), income $75,000+ (45.5% v 34.0%), index encounters in Psych units (46.5% v 5.9%), substance abuse (12.1% v 3.9%), anxiety (16% v 2.2%) and documented prior suicidal ideation (3.7% v 0.5%). Screening for STB identified 2.05% with any STB and 10.9% with MDD+STB. Characteristics differed based on risk and MDD status. Highlighting demographic and clinical differences between these patient groups can guide efforts to provide mental health consultation and referrals.

Plasma androgens and the presence and course of depression in a large cohort of men

BackgroundHypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms. MethodsIn 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5α-dihydrotestosterone (5α-DHT), and androstenedione were determined with liquid chromatography–tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years. ResultsNone of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5α-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms. ConclusionsThese results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms.

Increased telomerase activity in major depressive disorder with melancholic features: Possible role of pro-inflammatory cytokines and the brain-derived neurotrophic factor

The biological mechanisms responsible for depression symptoms are not yet understood. For this reason, it is important to reveal the etiopathogenetic mechanisms in this disease. This study aims to compare the levels of pro-inflammatory cytokines, Brain-Derived Neurotrophic Factor (BDNF), and telomerase activity in patients with major depressive disorder (MDD) and healthy controls. Plasma BDNF, interleukin-6 (IL-6), IL-1beta, and Tumor Necrosis Factor-alpha (TNF-alpha) levels, and telomerase activity were measured in 39 patients with major depression and 39 healthy controls matched with patients in terms of age, gender, and education year. Plasma concentration of BDNF, IL-6 levels, and telomerase activity was significantly different between patients with MDD and healthy controls. Correlation analysis showed a positive trend between plasma BDNF levels and plasma IL-6 levels in patients with MDD with melancholic features. Furthermore, the path analysis results showed that the telomerase activity was indirectly affected by gender, IL-1β, IL-6, BDNF, and BMI, via the severity of depression and anxiety and MDD status as the mediators. Further studies are needed to examine the molecular mechanism of the telomerase activity and the role of BDNF and pro-inflammatory cytokines in the telomerase activation in MDD.

Plasma androgens and the presence and course of depression in a large cohort of women

Major depressive disorder (MDD) has a higher prevalence in women with supraphysiologic androgen levels. Whether there is also an association between depression and androgen levels in the physiological range, is unknown. This study examined if women with current MDD have higher androgen levels compared to women who have never had MDD, and if androgen levels are associated with onset and remission of MDD. In 1659 women (513 current MDD, 754 remitted MDD, and 392 never MDD), baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulfate and sex hormone binding globulin (SHBG) with radioimmunoassays. Free testosterone was calculated. MDD status was assessed at baseline, and at 2 and 4 years follow-up. Women were aged between 18 and 65 years (mean age 41) with total testosterone levels in the physiological range (geometric mean 0.72 nmol/L [95% CI 0.27–1.93]). After adjusting for covariates and multiple testing, women with current MDD had a higher mean free testosterone than women who never had MDD (adjusted geometric mean 8.50 vs. 7.55 pmol/L, p = 0.0005), but this difference was not large enough to be considered clinically meaningful as it was consistent with statistical equivalence. Levels of other androgens and SHBG did not differ and were also statistically equivalent between the groups. None of the androgens or SHBG levels predicted onset or remission of MDD. Our findings support the idea that plasma androgens within the physiological range have no or only limited effects on depressive disorders in women.

Sex Differences in Hemoglobin A1c Levels Related to the Comorbidity of Obesity and Depression.

Background: Obesity (OB) and major depressive disorder (MDD) are chronic conditions associated with disease burden, and their comorbidity appears more common among women. Mechanisms linking these conditions may involve inflammatory and metabolic pathways. The goal of this study was to evaluate the impact of MDD on relationships between OB and cardiometabolic function, and sex differences therein. Materials and Methods: Adult offspring from the New England Family Studies (NEFS) were assessed at ages 39-50, including anthropometry, cardiometabolic profile assays, and metabolic syndrome. Individuals were grouped by body mass index (BMI) and MDD status: healthy weight with (n = 50) or without MDD (n = 95) and obese with (n = 79) or without MDD (n = 131). The interaction of (recurrent) MDD and BMI on cardiometabolic markers was tested using quantile regression models. Results: Participants with MDD exhibited significantly higher hemoglobin A1c (HbA1c) than those without MDD (5.60% vs. 5.35%, p < 0.05). Women with comorbid recurrent MDD and OB had higher HbA1c levels compared to obese women without MDD (5.75% vs. 5.44%, p < 0.05); an interaction between MDD and BMI status was not observed among men. Conclusions: We demonstrated sex differences in the interaction between BMI and recurrent MDD status on a primary biomarker for diabetes risk, suggesting a common metabolic pathway predisposing women to these comorbid conditions. Further investigation is needed to identify mechanisms that may lead to more effective, sex-dependent screening and therapies.

Predictive inflammatory biomarkers for change in suicidal ideation in major depressive disorder and panic disorder: A 12-week follow-up study

Previous studies have investigated the role of inflammatory markers in suicidality of patients with major depressive disorder (MDD) or panic disorder (PD). However, few studies have investigated associations between serum inflammatory cytokine levels and suicidality. We hypothesized that MDD and PD status might be significantly associated with serum inflammatory cytokines and that we could predict levels of improvement in suicide ideation intensity using serum inflammatory biomarkers in patients with MDD and PD. For this study, 41 patients with MDD, 52 patients with PD, and 59 healthy control (HC) subjects were enrolled. Psychological measurements and serum inflammatory markers such as interleukin (IL) −6, −10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and C reactive protein (CRP) were examined. A total of five visits were completed during 12 weeks. After controlling for confounding factors, log-transformed IL-6 (ln_IL-6) at baseline (MDD: 0.297 ± 0.626; PD: 0.342 ± 0.723; HC: −0.121 ± 0.858; p = 0.007, >0.0017, 0.05/30) and mean ln_IL-6 (MDD: 0.395 ± 0.550, PD: 0.249 ± 0.544, HC: −0.139 ± 0.622, p = 0.002, >0.0017, 0.05/30) levels were trends towards significantly higher in patients with MDD and PD than in HC. In MDD patients, a higher level of basal ln_TNF-α was a significant predictor of ΔSSI (changes in SSI scores between baseline and week 12) even after controlling for changes of depression symptoms and baseline SSI scores (standardized β = 0.541, p = 0.002 < 0.0028, 0.05/18). In conclusion, we could predict ΔSSI using baseline inflammatory biomarkers for patients with MDD.

Amplitude of low frequency fluctuations (ALFF) of spontaneous and induced rumination in major depression: An fNIRS study

In the current study, we investigated the amplitude of low frequency fluctuations (ALFF) at rest and during a rumination induction. Specifically, we explored the differences of cortical blood oxygenation using fNIRS in subjects with Major Depressive Disorder (MDD) and healthy controls (HC). Rumination was assessed as state and trait measure, as well as with a qualitative semi-structured interview. Qualitative and quantitative measures of rumination indicated that the MDD group showed elevated rumination regarding state and trait measures. Furthermore, rumination differed qualitatively between the groups. The MDD group showed higher levels of general rumination and increased rumination during the rumination induction. However, the MDD group did not show a carry-over effect of elevated rumination after the induction paradigm to the following resting-state measurement. On a neuronal level, we observed a general hypoactivity in the MDD group compared to the HC group. Moreover, both groups showed increased ALFF during the rumination induction compared to the rest phase, especially in temporo-parietal areas. However, no interaction effect of MDD status and rumination induction was found. The current findings are discussed with respect to the literature of paradigms used in the investigation of rumination and suggestions on general improvements in rumination research are given.

Multiple lifestyle factors and depressed mood: a cross-sectional and longitudinal analysis of the UK Biobank (N\u2009=\u200984,860)

BackgroundThere is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and how these relations may differ in individuals with major depressive disorder (MDD) and those without a depressive disorder, as ‘healthy controls’ (HC).MethodsTo this end, we assessed the relationships between 6 key lifestyle factors (measured via self-report) and depressed mood (measured via a relevant item from the Patient Health Questionnaire) in individuals with a history of or current MDD and healthy controls (HCs). Cross-sectional analyses were performed in the UK Biobank baseline sample, and longitudinal analyses were conducted in those who completed the Mental Health Follow-up.ResultsCross-sectional analysis of 84,860 participants showed that in both MDD and HCs, physical activity, healthy diet, and optimal sleep duration were associated with less frequency of depressed mood (all p < 0.001; ORs 0.62 to 0.94), whereas screen time and also tobacco smoking were associated with higher frequency of depressed mood (both p < 0.0001; ORs 1.09 to 1.36). In the longitudinal analysis, the lifestyle factors which were protective of depressed mood in both MDD and HCs were optimal sleep duration (MDD OR = 1.10; p < 0.001, HC OR = 1.08; p < 0.001) and lower screen time (MDD OR = 0.71; p < 0.001, HC OR = 0.80; p < 0.001). There was also a significant interaction between healthy diet and MDD status (p = 0.024), while a better-quality diet was indicated to be protective of depressed mood in HCs (OR = 0.92; p = 0.045) but was not associated with depressed mood in the MDD sample. In a cross-sectional (OR = 0.91; p < 0.0001) analysis, higher frequency of alcohol consumption was surprisingly associated with reduced frequency of depressed mood in MDD, but not in HCs.ConclusionsOur data suggest that several lifestyle factors are associated with depressed mood, and in particular, it calls into consideration habits involving increased screen time and a poor sleep and dietary pattern as being partly implicated in the germination or exacerbation of depressed mood.

Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults.

Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD.Methods: A final sample of 185 young, high-risk German adults (aged 18–35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes.Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls.Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.

The Diagnostic Value of the Combination of Serum Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor-1 for Major Depressive Disorder Diagnosis and Treatment Efficacy.

BackgroundLast decades of psychiatric investigations have been marked by a search for biological markers that can clarify etiology and pathogenesis, confirm the diagnosis, screen individuals at risk, define the severity, and predict the course of mental disorders. In our study, we aimed to evaluate if BDNF and IGF-1 serum concentrations separately and in combination might be used as biomarkers for major depressive disorder (MDD) diagnosis and treatment efficacy and to evaluate the relationships among those proteins and clinical parameters of MDD.MethodsForty-one MDD patients (according to DSM-5) and 32 healthy controls (HC) were included in this study. BDNF and IGF-1 serum concentrations, psychopathological (MADRS, CGI) and neuropsychological parameters (PDQ-5, RAVLT, TMT-B, DSST), functioning according to Sheehan Disability Scale were analyzed in all subjects at admission and 30 MDD patients after 8 weeks of vortioxetine treatment. Correlational analyses were performed to explore relationships between BDNF and IGF-1 and clinical characteristics. AUC-ROCs were calculated to determine if the value of serum BDNF and IGF-1 levels could serve for MDD diagnosis.ResultsMDD patients had significantly lower serum BDNF (727.6 ± 87.9 pg/ml vs. 853.0 ± 93.9 pg/ml) and higher serum IGF-1 levels (289.15 ± 125.3 ng/ml vs. 170.2 ± 58.2 ng/ml) compared to HC. Significant correlations were obtained between BDNF levels and MDD status, depressive episode (DE) severity, precipitating factors, executive functions disruption (TMT-B, RAVLT immediate recall scores) and all subdomains of functioning. As for IGF-1, correlations were found between IGF-1 level and MDD status, DE severity, number and duration of DE, parameters of subjective and objective cognitive functioning (PDQ-5, RAVLT, TMT-B, DSST scores), and all subdomains of functioning. The associations between IGF-1 concentrations and cognitive tests’ performance were stronger than those of BDNF. Separately both BDNF and IGF-1 demonstrated good discriminating ability for MDD diagnosis with AUC of 0.840 and 0.824, respectively. However, the combination of those neurotrophins had excellent diagnostic power to discriminate MDD patients from HC, providing an AUC of 0.916. Vortioxetine treatment significantly increased BDNF and attenuated IGF-1 serum concentrations, improved all psychopathological and neuropsychological parameters and functioning.ConclusionsThe combination of IGF-1 and BDNF might be considered as a diagnostic combination for MDD.

Deep learning-based classification of posttraumatic stress disorder and depression following trauma utilizing visual and auditory markers of arousal and mood.

Visual and auditory signs of patient functioning have long been used for clinical diagnosis, treatment selection, and prognosis. Direct measurement and quantification of these signals can aim to improve the consistency, sensitivity, and scalability of clinical assessment. Currently, we investigate if machine learning-based computer vision (CV), semantic, and acoustic analysis can capture clinical features from free speech responses to a brief interview 1 month post-trauma that accurately classify major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). N = 81 patients admitted to an emergency department (ED) of a Level-1 Trauma Unit following a life-threatening traumatic event participated in an open-ended qualitative interview with a para-professional about their experience 1 month following admission. A deep neural network was utilized to extract facial features of emotion and their intensity, movement parameters, speech prosody, and natural language content. These features were utilized as inputs to classify PTSD and MDD cross-sectionally. Both video- and audio-based markers contributed to good discriminatory classification accuracy. The algorithm discriminates PTSD status at 1 month after ED admission with an AUC of 0.90 (weighted average precision = 0.83, recall = 0.84, and f1-score = 0.83) as well as depression status at 1 month after ED admission with an AUC of 0.86 (weighted average precision = 0.83, recall = 0.82, and f1-score = 0.82). Direct clinical observation during post-trauma free speech using deep learning identifies digital markers that can be utilized to classify MDD and PTSD status.