Current Major Depressive Disorder Research Articles

Effects of group music therapy on depressive symptoms in women - The MUSED-study: Results from a randomized-controlled trial.

Music can directly influence emotions, the regulation of which are known to be impaired in major depressive disorder (MDD). While music therapy (MT) could be an effective complement to treat MDD, studies investigating such effects have not yet yielded conclusive results. We hypothesized that group music therapy (GMT) might lead to a significant reduction of depressive symptoms (DS). In a randomized controlled trial, 102 women with current MDD were randomly assigned to an intervention group receiving GMT or a waitlist control group. Data assessment was conducted pre- (T0), post- (T1), and at a 10-week follow-up to (T2) the intervention. DS as the primary outcome were assessed via observer-rated (Hamilton Depression Rating Scale, T0-T1), self-rated (Beck Depression Inventory, T0-T1-T2), and ecological momentary (T0-T1) assessments. Secondary effects on emotion and mood regulation strategies, and quality of life (QoL), were measured T0-T1-T2. The results suggest non-significant effects of the GMT on a descriptive level on self-reported and observer rated DS and statistically significant effects on DS in everyday life, QoL, and regulation strategies, with larger effects from T0-T1 than from T0-T1-T2. The generalizability is limited by the high dropout rate and data loss due to the COVID-19 pandemic, the fact that long-term effects of GMT are not assured, and the homogeneous gender (female) of the sample. GMT is an economical approach to treat MDD, yielding health-promoting effects regarding DS, emotion regulation, and QoL. Manualization and further evaluation of MT is strongly recommended.

Effects of Varenicline, Bupropion, Nicotine Patch, and Placebo on Treating Smoking Among Persons With Current or Past Major Depressive Disorder: Secondary Analysis of a Double-Blind, Randomized, Placebo-Controlled Trial.

The aim of this study was to compare the safety and efficacy of the leading smoking cessation medications among individuals with current versus past major depressive disorder (MDD). This was a secondary analysis of a randomized, double-blind trial over 12 weeks with varenicline or bupropion, followed by a 12-week assessment, in participants ages 18-75 with past (N=2,174) or current (N=451) MDD or without psychiatric disorders (N=4,028). Interventions included 12 weeks of pharmacotherapy with placebo, nicotine replacement therapy (NRT; nicotine patch), bupropion, or varenicline, and brief counseling. The primary safety outcome was occurrence of one or more moderate to severe neuropsychiatric adverse events. Efficacy was assessed as biochemically verified continuous abstinence during weeks 9-12. Among all 6,653 participants, the risk of neuropsychiatric adverse events did not differ by medication within the past-MDD, current-MDD, or nonpsychiatric cohorts. The MDD cohorts had higher risk difference (p<0.001) for neuropsychiatric adverse events compared with the nonpsychiatric cohort (past-MDD cohort, risk difference=-0.03, 95% CI=-0.05, -0.02; current-MDD cohort, risk difference=-0.02, 95% CI=-0.05, 0.00). Within the past-MDD cohort, the odds ratios compared with placebo were 3.0 (95% CI=2.0, 4.5) for varenicline, 2.1 (95% CI=1.6, 2.7) for bupropion, and 2.1 (95% CI=1.4, 3.2) for NRT. Within the current-MDD cohort, varenicline differed from placebo (odds ratio=2.67, 95% CI=1.2, 6.15) and NRT (odds ratio=2.93, 95% CI=1.2, 7.2). All medications were generally safe in both MDD cohorts. NRT and bupropion were not more effective than placebo for those with current MDD. Varenicline plus counseling may be the best treatment for individuals with past or current MDD, given its greater efficacy, similar risk of adverse events, and, for those with current depression, reductions in anxiety and depression while trying to quit smoking.

Depression with immuno-metabolic dysregulation: Testing pragmatic criteria to stratify patients

IntroductionInflammatory and metabolic processes are linked to depression, but only 25–30% of depressed patients show low-grade inflammation and metabolic dysregulation associated with atypical, energy-related symptoms (AES). Interventions targeting immuno-metabolic dysregulation could benefit depressed patients, but currently no consensus exists how to best select patients with immuno-metabolic dysregulations. Therefore, we investigated which combinations of circulating C-reactive protein (CRP) and AES could identify those depressed individuals with significant immuno-metabolic dysregulation. MethodsData are from 1,077 persons with a current Major Depressive Disorder (MDD) of the Netherlands Study of Depression and Anxiety. Immuno-metabolic markers were Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), glycoprotein acetyls, body mass index (BMI), waist circumference, triglycerides, high-density-lipoprotein cholesterol (HDL cholesterol), glucose and leptin. Strata for CRP (≤ 1, < 1 CRP ≤ 3, > 3 mg/L) and AES (score of ≤ 3, 4–5, ≥ 6) were compared on immuno-metabolic markers using analyses of covariance. ResultsAcross strata of CRP and AES, there was a dose–response pattern with all higher immuno-metabolic marker levels across higher strata of CRP and AES, with the exception for an association between AES and TNF-α. Persons with both elevated CRP (> 1 mg/L) and high AES (≥ 6) showed a more dysregulated inflammatory and metabolic profile compared to persons with lower CRP and/or AES (p < 0.001). ConclusionOur results show a dose–response relationship between both CRP levels and AES with immuno-metabolic risk biomarkers, indicating that CRP and AES combined can capture immuno-metabolic features of MDD. Combining these available and scalable indexes may be an effective strategy to select a patient sample with immuno-metabolic dysregulation who may benefit from treatments targeting inflammatory or metabolic pathways.

Neuroinflammation, Stress-Related Suicidal Ideation, and Negative Mood in Depression

Brain translocator protein 18k Da (TSPO) binding, a putative marker of neuroinflammatory processes (eg, gliosis), is associated with stress and elevated in depressed and suicidal populations. However, it is unclear whether neuroinflammation moderates the impact of daily life stress on suicidal ideation and negative affect, thereby increasing risk for suicidal behavior. To examine the association of TSPO binding in participants with depression with real-world daily experiences of acute stress-related suicidal ideation and negative affect, as well as history of suicidal behavior and clinician-rated suicidal ideation. Data for this cross-sectional study were collected from June 2019 through July 2023. Procedures were conducted at a hospital-based research center in New York, New York. Participants were recruited via clinical referrals, the Columbia University research subject web portal, and from responses to internet advertisements. Of 148 participants who signed informed consent for study protocols, 53 adults aged 18 to 60 years who met DSM-5 diagnostic criteria for current major depressive disorder completed procedures with approved data and were enrolled. Participants were free of schizophrenia spectrum disorders, active physical illness, cognitive impairment, and substance intoxication or withdrawal at the time of scan. All participants underwent positron emission tomography imaging of TSPO binding with 11C-ER176 and concurrent arterial blood sampling. A weighted average of 11C-ER176 total distribution volume (VT) was computed across 11 a priori brain regions and made up the primary outcome measure. Clinician-rated suicidal ideation was measured via the Beck Scale for Suicidal Ideation (BSS). A subset of participants (n = 21) completed 7 days of ecological momentary assessment (EMA), reporting daily on suicidal ideation, negative affect, and stressors. In the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), 11C-ER176 VT was associated at trend levels with clinician-rated suicidal ideation severity (β, 0.19; 95% CI, -0.03 to 0.39; P = .09) and did not differ by suicide attempt history (n = 15; β, 0.18; 95% CI, -0.04 to 0.37; P = .11). Exploratory analyses indicated that presence of suicidal ideation (on BSS or EMA) was associated with higher 11C-ER176 VT (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, 11C-ER176 VT was associated with greater suicidal ideation and negative affect during EMA periods with stressors compared with nonstress periods (β, 0.12; SE, 0.06; 95% CI, 0.01 to 0.23; P = .03 and β, 0.19; SE, 0.06; 95% CI, 0.08 to 0.30; P < .001, respectively). TSPO binding in individuals with depression may be a marker of vulnerability to acute stress-related increases in suicidal ideation and negative affect. Continued study is needed to determine the causal direction of TSPO binding and stress-related suicidal ideation or negative affect and whether targeting neuroinflammation may improve resilience to life stress in patients with depression.

Traumatic Brain Injury in U.S. Veterans: Prevalence and Associations with Physical, Mental, and Cognitive Health

Objective: To examine the prevalence of traumatic brain injury (TBI) in the U.S. veteran population, and physical, mental, and cognitive health conditions associated with TBI. Design: Retrospective cohort study. Setting: A nationally representative sample of U.S. military veterans surveyed in 2019-2020. ParticipantsVeterans with probable TBI (n=943; M=58.8 years, SD=16.4; 75.9% non-Hispanic White) and without probable TBI (n=3,033; M=63.3 years, SD=15.3; 78.6% non-Hispanic White) were categorized based on a 2-item modified Veterans Health Administration TBI screen or self-reported health professional diagnoses of concussion/TBI. InterventionsNot applicable. Main Outcome Measure(s)Self-reported health professional-diagnosed physical and cognitive health conditions, disability with basic and instrumental activities of daily living (ADLs), positive screens for posttraumatic stress disorder (PTSD), major depressive disorder (MDD), anxiety disorder, alcohol use disorder (AUD), or drug use disorder (DUD), and current suicidal ideation or prior suicide attempts. ResultsAmong the full sample, 24.5% (95% confidence interval: 22.7, 26.3) had probable TBI. In adjusted analyses, probable TBI was independently associated with greater odds of rheumatoid arthritis (odds ratio [OR]=2.06), chronic pain (OR=1.87), kidney disease (OR=1.81), pulmonary disease (OR=1.74), arthritis (OR=1.65), migraine (OR=1.59), sleep disorders (OR=1.57), and osteoporosis or osteopenia (OR=1.51). Veterans with probable TBI also had higher odds of mild cognitive impairment (OR=4.53) and disability with ADLs (OR=2.18) and instrumental ADLs (OR=1.98), although ADL disability was explained by other physical health conditions. Probable TBI was associated with higher odds of probable current anxiety disorder (OR=2.82), MDD (OR=2.17), suicidal ideation (OR=1.78), PTSD (OR=1.72), DUD (OR=1.54), and AUD (OR=1.47). Conclusions: Nearly 1-in-4 U.S. veterans screen positive for probable TBI, which was associated with several physical and mental health conditions that adversely affect health and functioning. Results underscore the importance of multidisciplinary interventions that concurrently target the unique physical, mental, cognitive, and functional health needs of this population.

Social contexts are associated with higher emotional awareness than nonsocial contexts: Evidence in a sample of people with and without major depressive disorder.

Growing evidence suggests that social contexts may prompt qualitatively distinct experiences of emotions than nonsocial contexts. In this study of people's naturalistic daily emotional experiences, we examined in adults with and without major depressive disorder (MDD) whether experiencing emotions in a social context (with others) versus nonsocial context (without others) was associated with greater emotional clarity and attention to one's emotional experience (i.e., emotional awareness). Based on evidence that social stimuli are highly salient to social species, we predicted that interactions with social others-and especially close social others-would be associated with greater emotional awareness. We furthermore expected that individuals with MDD, who tend to have diminished emotional clarity and social deficits, might experience less emotional awareness in social settings than healthy controls. Across a 2-week experience sampling study that concluded in 2019, we assessed emotional awareness when people were interacting with others (vs. not) and interacting with close (vs. nonclose) others among adults with current MDD (n = 53), remitted MDD (n = 80), and healthy controls (n = 87). As expected, attention to emotion and emotional clarity were higher in social versus nonsocial contexts and when interacting with close versus nonclose others. Contrary to expectations that these effects would be weaker among those with current MDD, the current MDD group showed enhanced emotional clarity in social versus nonsocial settings compared to the other two groups. Insofar as emotional clarity is beneficial to well-being, these findings suggest those with MDD may especially benefit from social contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A randomized controlled trial of a self-guided mobile app targeting repetitive negative thought to prevent depression in university students: study protocol of the Nurture-U Reducing Worry prevention trial

BackgroundTackling poor mental health in university students has been identified as a priority in higher education. However, there are few evidence-based prevention initiatives designed for students. Repetitive Negative Thought (RNT, e.g. worry, rumination) is elevated in university students and is a well-established vulnerability factor for anxiety and depression. Furthermore, there are now evidence-based cognitive-behavioural interventions to tackle RNT. A mobile self-help cognitive-behavioural app targeting RNT, adapted for students may therefore be an effective, scalable, and acceptable way to improve prevention in students.MethodsAn online single blind, two-arm parallel-group Randomised Controlled Trial (RCT) to examine the incidence of major depression and symptoms of anxiety and depression across 12 months in university students aged over 16 who screen into the study with self-reported high levels of worry and/or rumination and no current diagnosis of major depression. Eligible participants will be randomised to the active intervention arm (usual practice plus using a self-guided mobile app targeting RNT) or to the control arm (usual practice). In total, 648 participants aged over 16, with no current major depression, bipolar disorder or psychosis will be recruited from UK universities. Assessments will take place at baseline (pre-randomisation), 3 months and 12 months post- randomisation. Primary endpoint and outcome is incidence of major depression as determined by self-reported diagnostic criteria at 12-month follow-up. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and academic outcomes are secondary outcomes. Compliance, adverse events, and potentially mediating variables will be carefully monitored.DiscussionThe trial aims to provide a better understanding of the causal role of tackling RNT (worry, rumination) using a self-help mobile app with respect to preventing depression in university students. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective mobile-health public health strategies for preventing common mental health problems.Trial registrationhttps://www.isrctn.com/ISRCTN86795807 Date of registration: 27 October 2022

The burden of brooding on neural error processing: The role of repetitive negative thinking in major depressive disorder with and without comorbid anxiety disorders

BackgroundRepetitive negative thinking (RNT), particularly its brooding aspect, is a prominent feature in Major Depressive Disorder (MDD) with and without comorbid anxiety. Error processing, an adaptive cognitive operation, seems to be impaired in individuals with exaggerated RNT. This study measured a post-error neural response, error-related negativity (ERN), during an inhibitory task to examine the mechanism underlying the relationship between RNT and faulty error processing. MethodsWe examined current MDD patients with (n = 61) and without comorbid anxiety disorders (COM; n = 38), propensity-matched into High- or Low-RNT groups according to Ruminative Response Scale Brooding subscale scores. Using 32-channel electroencephalography (EEG) during a stop-signal task, we measured baseline-corrected ERN amplitude at FCz 0–100 ms after an incorrect response. A between-subjects ANOVA was conducted with group (High RNT, Low RNT) and comorbidity (MDD, COM) as factors. ResultsA significant group-by-comorbidity interaction (η2 = 0.07) was found, with MDD participants exhibiting high RNT revealing smaller (more positive) ERN amplitudes compared to their COM counterparts with high RNT (d = 0.77) and MDD participants with low RNT (d = 0.92). ConclusionsNon-anxious individuals with MDD and high RNT showed blunted post-error neural responses, potentially indicating a diminished adaptive neural mechanism for recognizing and correcting errors. However, the presence of comorbid anxiety disorders in individuals with high RNT appears to counteract this reduction, potentially through an enhanced neural response to errors, thereby maintaining a higher level of error-processing activity. Further understanding of these relationships is essential for developing targeted interventions for MDD, with particular focus on the detrimental impact of brooding RNT.

Childhood Trauma Questionnaire-based child maltreatment profiles to predict efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus non-specific psychotherapy in adults with early-onset chronic depression: cluster analysis of data from a randomised controlled trial

Child maltreatment is a broadly confirmed risk factor for mental and physical illness. Some psychological treatments specifically target mental health conditions associated with child maltreatment. For example, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) focuses on maladaptive interpersonal behaviours in chronic depression. However, how the assessment of child maltreatment could inform personalised treatment is unclear. We used data from a previously published clinical trial to investigate whether a pre-established child maltreatment clustering approach predicts differential outcomes after CBASP versus non-specific supportive psychotherapy in patients with early-onset chronic depression. We did a cluster analysis of data from a previous randomised controlled trial of unmedicated adult outpatients with early-onset chronic depression who were treated at eight university clinics and psychological institutes in Germany with 32 sessions of CBASP or non-specific supportive psychotherapy. Participants were eligible for the original trial if they were aged 18-65 years; had major depressive disorder (MDD) with an early onset and duration of at least 2 years, current MDD superimposed on a pre-existing dysthymic disorder, or recurrent MDD with incomplete remission between episodes as defined by DSM-IV; and had a score of at least 20 points on the 24-item Hamilton Rating Scale for Depression (HRSD-24). Participants were included in the current study if they had completed the short form of the Childhood Trauma Questionnaire (CTQ) at trial baseline. We used an agglomerative hierarchical clustering approach to derive child maltreatment clusters from individual patterns across the five domains of the CTQ. We used linear mixed models to investigate whether clustering could predict differential clinical outcomes (change in symptom severity on the HRSD-24) up to 2 years after treatment onset. People with lived experience were involved in the current study. 253 patients (129 [51%] treated with CBASP and 124 [49%] with supportive psychotherapy) had complete CTQ records and were included in the analysis. 169 (67%) participants were women, 84 (33%) were men, and the mean age was 45·9 years (SD 11·7). We identified seven child maltreatment clusters and found significant differences in treatment effects of CBASP and supportive psychotherapy between the clusters (F(6,948·76)=2·47; p=0·023); differences were maintained over the 2-year follow-up. CBASP was superior in distinct clusters of co-occurring child maltreatment: predominant emotional neglect (change in β -6·02 [95% CI -11·9 to -0·13]; Cohen's d=-0·98 [95% CI -1·94 to -0·02]; p=0·045), predominant emotional neglect and abuse (-6·39 [-10·22 to -2·56]; -1·04 [-1·67 to -0·42]; p=0·0011), and emotional neglect and emotional and physical abuse (-9·41 [-15·91 to -2·91]; -1·54 [-2·6 to -0·47]; p=0·0046). CTQ-based cluster analysis can facilitate identification of patients with early-onset chronic depression who would specifically benefit from CBASP. Child maltreatment clusters could be implemented in clinical assessments and serve to develop and personalise trauma-informed care in mental health. The German Research Foundation and the German Federal Ministry of Education and Research.

Excessive Daytime Sleepiness in Hypertensive Patients: The Role of Major Depressive Disorder.

There is a special relationship between major depressive disorder and excessive daytime sleepiness. However, given the negative impact of excessive daytime sleepiness on life quality and cardiovascular outcome in hypertensive patients, the objective of this study was to investigate the potential role played by major depressive disorder in the occurrence of this complaint for this particular subpopulation. Data from 1404 hypertensive patients recruited from the Sleep Unit's polysomnographic recordings database were analyzed. A score >10 on the Epworth Sleepiness Scale was used to define excessive daytime sleepiness in this study. Logistic regression analyses were performed to investigate the risk of excessive daytime sleepiness associated with major depressive disorder in hypertensive patients. Excessive daytime sleepiness was frequent (40.0%) in our sample of hypertensive patients. After adjustments for major confounding factors, multivariate logistic regression analyses demonstrated that unlike remitted major depressive disorder, only current major depressive disorder was associated with a higher risk of excessive daytime sleepiness in hypertensive patients. Given this potential implication of current major depressive disorder in the occurrence of excessive daytime sleepiness for hypertensive patients, it is therefore essential to achieve the complete remission of this psychiatric disorder to avoid negative consequences associated with this complaint in this particular subpopulation.

Successful Aging in US Veterans with Mental Disorders: Results From the National Health and Resilience in Veterans Study

ObjectivesTo determine the prevalence and correlates of successful aging in US veterans who screened positive for current major depressive disorder (MDD), generalized anxiety disorder (GAD), and/or posttraumatic stress disorder (PTSD). MethodsIn a nationally representative sample of 475 US military veterans (mean age=58.3, SD=14.7; range 24–92) who screened positive for MDD, GAD, and/or PTSD, multivariable logistic regression and relative importance analyses were conducted to identify independent correlates of successful aging. ResultsOne-in-five (20.6%) veterans rated themselves as aging successfully. Resilience and gratitude were the strongest positive correlates of successful aging, accounting for 38.1% and 32.4% of the explained variance, respectively. Greater somatic symptoms were the strongest negative correlate, accounting for 11.2% of the explained variance. Higher gratitude moderated the negative association between somatic symptoms and successful aging. ConclusionsPositive psychiatry interventions targeting psychosocial factors such as resilience and gratitude may help promote successful aging among US veterans with mental disorders.

Psychological Pain, Hopelessness and Suicide Ideation in Female Patients with Fibromyalgia.

Objective: The aim of this study was to investigate if psychache and hopelessness may serve as reliable predictors of suicidal ideation among female fibromyalgia (FM) patients. This was a cross-sectional study of 50 women with FM, examining the relationship between psychological pain, hopelessness, depressive symptoms, and suicidal ideation. FM diagnosis was confirmed by the American College of Rheumatology (ACR) criteria. Demographic data, the Mini International Neuropsychiatric Interview (MINI 7.0.2), the Beck Depression Inventory-II (BDI-II), the Beck Hopelessness Scale (BHS), the Pittsburgh Sleep Quality Index (PSQI) and the Psychache Scale were utilized to assess these relationships and their predictive value for suicidality. The mean age of the participants was 50.2 years (±8.7). Thirty-two (64%) patients had current major depression, 11 (22%) had bipolar disorder, 20 (40%) presented passive suicidal ideation and 14 (28%) presented active suicidal ideation. Psychological pain correlated with both depressive symptoms (p<0.01; r= 0.648) and hopelessness (p=0.029; r=0.312) but did not predict suicidal ideation. Logistic regression analyses revealed depressive symptom severity as a predictor of passive suicidal ideation (odds ratio = 1.486; 95% CI: 1.017 - 2.170), while hopelessness predicted active suicidal ideation (odd ratio = 1.356; 95% CI, 1.049 - 1.753). FM female patients showed increased prevalence of suicidal ideation. Hopelessness predicts active suicidal ideation but psychological pain did not serve as predictive factor for suicide ideation among female FM patients.

Risk of Comorbid Insomnia Disorder Associated with Major Depression in Apneic Patients: A Cross-Sectional Study.

Given the limitations of available studies, the objective of this study was to explore the role played by current and remitted major depression in the occurrence of comorbid insomnia disorder for apneic patients. Data from 1488 apneic patients were extracted from the medical reports of polysomnographic recordings available in the database of the Sleep Laboratory. The presence of comorbid insomnia disorder in these apneic patients was defined based on the diagnostic criteria of the American Academy of Sleep Medicine Work Group. The risk of comorbid insomnia disorder associated with current or remitted major depression in apneic patients was investigated using multivariate logistic regression models. After adjustment for the main confounding factors, multivariate logistic regression analyses revealed that remitted and current major depression were significantly associated with the occurrence of comorbid insomnia disorder in apneic patients. The findings of this study seem to indicate that comorbid insomnia disorder could be a residual symptom and a marker of major depression in apneic patients, which justifies the establishment of an adequate treatment for major depressive episodes and their potential residual symptoms to allow the better management of comorbid insomnia disorder and the better prevention of its potential negative consequences in this particular subpopulation.

Blunted stimulus-preceding negativity during reward anticipation in major depressive disorder

BackgroundReward processing dysfunction is a core characteristic of major depressive disorder (MDD), yet event-related potential (ERP) research in MDD has predominantly focused on reward receipt as opposed to anticipation. The stimulus-preceding negativity (SPN) ERP reflects anticipatory brain processing. This study examines whether individuals with MDD exhibit deficits during reward anticipation as evidenced by altered SPN amplitude. MethodsWe assessed prefeedback-SPN amplitudes during a monetary incentive delay (MID) task in individuals with MDD (n = 142, 99 with comorbid anxiety disorders [MDD + ANX]) compared to Controls (n = 37). A mixed analysis of variance was performed on prefeedback-SPN amplitude and behavioral measures, with group (MDD, MDD + ANX, Control) as the between-subjects factor, and feedback (gain, loss) and electrode (F3, F4, Fz, C3, C4, Cz, P3, P4, Pz) as within-subjects factors. ResultsA group main effect revealed faster reaction times for the Control group than MDD and MDD + ANX groups. A group x feedback interaction indicated that the MDD subgroup had smaller prefeedback-SPN amplitudes than MDD + ANX and Control groups when anticipating gain feedback. Additionally, individuals with current MDD, irrespective of past MDD and comorbid anxiety, exhibited smaller SPN amplitudes than Controls prior to gain feedback. LimitationsThe MID paradigm, designed for functional magnetic resonance imaging (fMRI) data acquisition, lacks optimization for ERP analysis. Moreover, the clinical groups included more females than the Control group. ConclusionsReduced resource allocation to reward anticipation may differentiate MDD from MDD + ANX and Control groups. Further investigation of the neural mechanisms of distinct MDD phenotypes is warranted.

Prevalence and correlates of common mental disorders among participants of the Uganda Genome Resource: Opportunities for psychiatric genetics research

Genetics research has potential to alleviate the burden of mental disorders in low- and middle-income-countries through identification of new mechanistic pathways which can lead to efficacious drugs or new drug targets. However, there is currently limited genetics data from Africa. The Uganda Genome Resource provides opportunity for psychiatric genetics research among underrepresented people from Africa. We aimed at determining the prevalence and correlates of major depressive disorder (MDD), suicidality, post-traumatic stress disorder (PTSD), alcohol abuse, generalised anxiety disorder (GAD) and probable attention-deficit hyperactivity disorder (ADHD) among participants of the Uganda Genome Resource. Standardised tools assessed for each mental disorder. Prevalence of each disorder was calculated with 95% confidence intervals. Multivariate logistic regression models evaluated the association between each mental disorder and associated demographic and clinical factors. Among 985 participants, prevalence of the disorders were: current MDD 19.3%, life-time MDD 23.3%, suicidality 10.6%, PTSD 3.1%, alcohol abuse 5.7%, GAD 12.9% and probable ADHD 9.2%. This is the first study to determine the prevalence of probable ADHD among adult Ugandans from a general population. We found significant association between sex and alcohol abuse (adjusted odds ratio [AOR] = 0.26 [0.14,0.45], p < 0.001) and GAD (AOR = 1.78 [1.09,2.49], p = 0.019) respectively. We also found significant association between body mass index and suicidality (AOR = 0.85 [0.73,0.99], p = 0.041), alcohol abuse (AOR = 0.86 [0.78,0.94], p = 0.003) and GAD (AOR = 0.93 [0.87,0.98], p = 0.008) respectively. We also found a significant association between high blood pressure and life-time MDD (AOR = 2.87 [1.08,7.66], p = 0.035) and probable ADHD (AOR = 1.99 [1.00,3.97], p = 0.050) respectively. We also found a statistically significant association between tobacco smoking and alcohol abuse (AOR = 3.2 [1.56,6.67], p = 0.002). We also found ever been married to be a risk factor for probable ADHD (AOR = 2.12 [0.88,5.14], p = 0.049). The Uganda Genome Resource presents opportunity for psychiatric genetics research among underrepresented people from Africa.

Campbell's 1953 Book on “Manic-Depressive Disease”

Abstract The DSM-III symptomatic criteria for major depression (MD) were derived from those proposed by Feighner and colleagues in 1972, which closely resembled those published by Cassidy in 1957. I here present a counter-factual history in which Feighner carefully read a key reference in Cassidy, a large 1953 follow-up study by Campbell of depressed patients with detailed tables of depressive signs and symptoms. In this alternative timeline, the Feighner criteria for MD were modified by Campbell's results, which then changed DSM-III and subsequent MD criteria sets. The historical pathway to the current DSM MD criteria was contingent on a range of historical events and could easily have been different. This story is not meant to criticize DSM MD criteria that perform well. Rather, it suggests that these criteria represent a useful but fallible set of symptoms/signs that index but do not constitute MD and therefore are not to be reified.

Integrative Modeling of Accelerometry-Derived Sleep, Physical Activity, and Circadian Rhythm Domains With Current or Remitted Major Depression

Accelerometry has been increasingly used as an objective index of sleep, physical activity, and circadian rhythms in people with mood disorders. However, most prior research has focused on sleep or physical activity alone without consideration of the strong within- and cross-domain intercorrelations; and few studies have distinguished between trait and state profiles of accelerometry domains in major depressive disorder (MDD). To identify joint and individual components of the domains derived from accelerometry, including sleep, physical activity, and circadian rhythmicity using the Joint and Individual Variation Explained method (JIVE), a novel multimodal integrative dimension-reduction technique; and to examine associations between joint and individual components with current and remitted MDD. This cross-sectional study examined data from the second wave of a population cohort study from Lausanne, Switzerland. Participants included 2317 adults (1164 without MDD, 185 with current MDD, and 968 with remitted MDD) with accelerometry for at least 7 days. Statistical analysis was conducted from January 2021 to June 2023. Features derived from accelerometry for 14 days; current and remitted MDD. Logistic regression adjusted for age, sex, body mass index, and anxiety and substance use disorders. Among 2317 adults included in the study, 1261 (54.42%) were female, and mean (SD) age was 61.79 (9.97) years. JIVE reduced 28 accelerometry features to 3 joint and 6 individual components (1 sleep, 2 physical activity, 3 circadian rhythms). Joint components explained 58.5%, 79.5%, 54.5% of the total variation in sleep, physical activity, and circadian rhythm domains, respectively. Both current and remitted depression were associated with the first 2 joint components that were distinguished by the salience of high-intensity physical activity and amplitude of circadian rhythm and timing of both sleep and physical activity, respectively. MDD had significantly weaker circadian rhythmicity. Application of a novel multimodal dimension-reduction technique demonstrates the importance of joint influences of physical activity, circadian rhythms, and timing of both sleep and physical activity with MDD; dampened circadian rhythmicity may constitute a trait marker for MDD. This work illustrates the value of accelerometry as a potential biomarker for subtypes of depression and highlights the importance of consideration of the full 24-hour sleep-wake cycle in future studies.

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.

Inflammation and immune system pathways as biological signatures of adolescent depression—the IDEA-RiSCo study

The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world’s adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14–16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.

Burnout among community service doctors in South Africa.

Burnout in doctors is an important issue with far-reaching consequences. Community service doctors may be particularly vulnerable because of their specific roles (rural settings, junior positions and reduced supervision). This study aimed to determine the prevalence of burnout among community service doctors in South Africa (SA), the potential contributory and protective factors and the consequences thereof. This was a national study of community service doctors in SA. A quantitative, descriptive cross-sectional study was performed. The Maslach Burnout Inventory was used to measure burnout. The online questionnaire also included demographic data, workplace and individual characteristics. Of the 208 community service doctors analysed, 89% and 94% had high emotional exhaustion and depersonalisation, respectively, while 97% had a low personal accomplishment. Mental illness, financial difficulties, unmanageable volume of patients and female gender were found to be potential contributory factors. Having manageable patient volumes, satisfaction with their decision to study medicine, talking to colleagues and feeling supported by healthcare facility management were among the significant potential protective factors. Significant potential consequences of burnout included: leaving the government sector, ever being diagnosed with a mental illness, using alcohol as a coping mechanism and possible current major depression. Burnout among community service doctors in SA is highly prevalent with significant potential consequences. There are a number of modifiable possible contributory and protective factors identified that may be targets for mental health interventions.Contribution:Healthcare burnout research is lacking in the African and specifically SA context. This void includes community service doctors.