Onset Of Major Depressive Disorder Research Articles

Maternal suicidality interacts with blunted reward processing to prospectively predict increases in depressive symptoms in 8-to-14-year-old girls

Both a hypoactive reward system and maternal depression are associated with the onset of Major Depressive Disorder (MDD) in youth. Recent research indicates that blunted reward processing and maternal history of depression may interact to predict increases in depressive symptoms, however, the role of specific maternal depressive symptoms has not been examined. The current study investigated whether maternal depressive symptoms, history of MDD, and suicidal thoughts and/or behaviors (STBs) might lead to prospective increases in depressive symptoms one year later in the context of hypoactive reward processing. In a sample (N = 212) of 8 to 14-year-old girls, we assessed depressive symptoms in youth at baseline and follow up, while reward processing was measured using the Reward Positivity (RewP) event-related brain potential. Maternal STBs, current depressive symptoms, and history of maternal MDD were assessed at baseline. The results indicated that only girls with a blunted RewP and maternal STBs exhibited increased depressive symptoms one year later. These results were not evident when maternal depressive symptoms or maternal history of MDD was examined as the moderator. Overall, the current study provides evidence that maternal STBs uniquely impact youth with blunted reward processing.

Pre-enlistment Anger Attacks and Postenlistment Mental Disorders and Suicidality Among US Army Soldiers

Anger is linked to adverse outcomes in military populations; however, whether pre-enlistment anger attacks are associated with postenlistment mental disorders and suicidality is unknown. To explore the associations of pre-enlistment anger attacks with postenlistment mental health. In this observational cohort study, the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) New Soldier Study (NSS) surveyed soldiers entering basic training from April 2011 to November 2012, with a subsample recruited for wave 1 of the STARRS Longitudinal Study (STARRS-LS) (conducted September 2016 to April 2018). Participants were recruited from 3 US Army installations for the NSS survey. Those who were subsequently contacted for STARRS-LS completed the follow-up survey via web or telephone. Prospective analyses were based on a weighted NSS subsample included in wave 1 of STARRS-LS. Data were analyzed from May 22, 2020, to March 17, 2021. History of anger attacks at baseline (NSS). Survey responses were used to classify new soldiers as having nonimpairing anger attacks (>2 attacks without interference in work or personal life), impairing anger attacks (>2 attacks with interference in work or personal life), or no significant history of anger attacks. Baseline analyses examined sociodemographic and clinical correlates of a history of anger attacks. Prospective logistic regression models estimated associations of baseline history of anger attacks with new onset and persistence of posttraumatic stress disorder, major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder, mania/hypomania, substance use disorder, suicidal ideation, and suicide attempt at wave 1 of STARRS-LS. Of the 38 507 baseline participants (83.0% male and 17.0% female; mean [SD] age, 20.97 [3.57] years), 6216 were selected for and completed wave 1 of the STARRS-LS. Baseline prevalence (SE) of nonimpairing and impairing anger attacks was 8.83% (0.16%) and 5.75% (0.15%), respectively. Prospective models showed that impairing anger attacks were associated with new onset of MDD (adjusted odds ratio [AOR], 1.98; 95% CI, 1.31-2.99), GAD (AOR, 2.39; 95% CI, 1.66-3.45), panic disorder (AOR, 2.02; 95% CI, 1.34-3.05), and suicidal ideation (AOR, 2.11; 95% CI, 1.45-3.07). When baseline psychiatric comorbidity was controlled for, impairing attacks remained associated with onset of GAD (AOR, 1.75; 95% CI, 1.19-2.58) and suicidal ideation (AOR, 1.62; 95% CI, 1.09-2.42). Anger attacks were not significantly associated with persistence of pre-enlistment mental disorders. The findings of this study suggest that a pre-enlistment history of impairing anger attacks may be associated with elevated risk of developing GAD, MDD, and suicidality after enlistment. Detection of impairing anger attacks could aid in assessing psychiatric risk in new soldiers.

Identification of DNA Methylation Changes That Predict Onset of Post-traumatic Stress Disorder and Depression Following Physical Trauma.

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly experienced after exposure to highly stressful events, including physical trauma, yet, biological predictors remain elusive. Methylation of DNA may provide key insights, as it likely is reflective of factors that may increase the risk in trauma patients, as DNA methylation is altered by previous stressors. Here, we compared DNA methylation patterns using bisulfite sequencing in patients with a physical trauma that required more than a 24-h hospitalization (n = 33). We then compared DNA methylation in patients who developed and compared the following groups (1) PTSD and MDD; n = 12), (2) MDD (patients with MDD only; n = 12), and (3) control (patients who did not have PTSD or MDD; n = 9), determined by the PTSD Checklist (PCL-5) and Quick Inventory of Depressive Symptomatology (QIDS) at 6-months follow-up. We identified 17 genes with hypermethylated cytosine sites and 2 genes with hypomethylated sites in comparison between PTSD and control group. In comparison between MDD and control group, we identified 12 genes with hypermethylated cytosine sites and 6 genes with hypomethylated sites. Demethylation of these genes altered the CREB signaling pathway in neurons and may represent a promising therapeutic development target for PTSD and MDD. Our findings suggest that epigenetic changes in these gene regions potentially relate to the onset and symptomology of PTSD and MDD and could be used as potential biomarkers in predicting the onset of PTSD or MDD following traumatic events.

Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression.

Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

Transthyretin as a Biomarker to Predict and Monitor Major Depressive Disorder Identified by Whole-Genome Transcriptomic Analysis in Mouse Models.

Background: Accumulations of stressful life events result in the onset of major depressive disorder (MDD). Comprehensive genomic analysis is required to elucidate pathophysiological changes and identify applicable biomarkers. Methods: Transcriptomic analysis was performed on different brain parts of a chronic mild stress (CMS)-induced MDD mouse model followed by systemic analysis. QPCR and ELISA were utilized for validation in mice and patients. Results: The highest numbers of genes with significant changes induced by CMS were 505 in the amygdala followed by 272 in the hippocampus (twofold changes; FDR, p < 0.05). Enrichment analysis indicated that the core-enriched genes in CMS-treated mice were positively enriched for IFN-γ response genes in the amygdala, and hedgehog signaling in the hippocampus. Transthyretin (TTR) was severely reduced in CMS-treated mice. In patients with diagnosed MDD, serum concentrations of TTR were reduced by 48.7% compared to controls (p = 0.0102). Paired samples from patients with MDD demonstrated a further 66.3% increase in TTR at remission compared to the acute phase (p = 0.0339). Conclusions: This study provides comprehensive information on molecular networks related to MDD as a basis for further investigation and identifies TTR for MDD monitoring and management. A clinical trial with bigger patient cohort should be conducted to validate this translational study.

Depression in Amputation Patients

Amputation alters the quality of life with an undeniable negative somatic and functional impact. The patient’s general mobility is impaired and there is an increase in metabolic needs as well as pain and discomfort. Etiologies are quite diverse: essentially vascular pathologies (74%) for the lower limbs and trauma related (61%) for the upper limbs. Thus, an important number of patients have to face amputation-related consequences. Pain (stump, phantom limb, back pain) is frequently described in 65 to 75% of patients after an amputation as well as the common onset of major depressive disorders for 35% of them. With the incidence of depression after limb amputation increasing in the patients, we sought to summarize the management of depression in amputation patients.

The impact of self-efficacy on first onset and prognosis of major depressive disorder: findings from a longitudinal study in a sample of Chinese first-year university students.

Self-efficacy is a pivotal factor in the etiology and prognosis of major depression. However, longitudinal studies on the relationship between self-efficacy and major depressive disorder (MDD) are scarce. The objectives were to investigate: (1) the associations between self-efficacy and the 1-year and 2-year risks of first onset of MDD and (2) the associations between self-efficacy and the 1-year and 2-year risks of the persistence/recurrence of MDD, in a sample of first-year university students. We followed 8079 first-year university students for 2 years from April 2018 to October 2020. MDD was ascertained by the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0) based on self-report. Self-efficacy was measured by the 10-item General Self-efficacy (GSE) scale. Random effect logistic regression modeling was used to estimate the associations. Among participants without a lifetime MDD, the data showed that participants with high baseline GSE scores were associated with a higher risk of first onset of MDD over 2 years [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08]. Among those with a lifetime MDD, participants with high baseline GSE scores were less likely to have had a MDD over 2 years (OR 0.93, 95% CI 0.88-0.99) compared to others. A high level of GSE may be protective of the risk of persistent or recurrent MDD. More longitudinal studies in university students are needed to further investigate the impact of GSE on the first onset of MDD.

Associations between borderline personality disorder features and the risk of first onset major depressive disorder: Findings from a 2-year longitudinal study in a sample of first-year university students in China

Background: The objective of this study was to estimate the associations between specific BPD features on the risk of first onset MDD over 2 years and to investigate the roles of sex, baseline depression and anxiety in the associations. Methods: A longitudinal study of Chinese first-year university students aged between 15 and 24 years and who did not have a lifetime MDD (n = 7,627). Random effect logistic regression modeling was used to estimate the associations between specific BPD features, the number of BPD features, and the risk of MDD. Results: The feeling of emptiness (OR = 2.14, 95% CI: 1.57, 2.92), paranoid/ dissociation (OR = 2.01, 95% CI: 1.43, 2.82), affective instability (OR = 1.71, 95% CI: 1.22, 2.39) conferred significant risk of MDD. Baseline depression and anxiety interacted with unstable relationship, identity disturbance and paranoid/disassociation in relation to the risk of MDD. A higher number of BPD features is associated with an increased risk of MDD. Limitations: Data collection relied on self-report. Thus, recall and reporting biases are possible. Due to the pandemic public health restrictions, we had to change the method of data collection at second annual assessment, which resulted in a lower response rate (66.5%). Conclusions: Mental health professionals should pay attention to the presence of BPD features in youth and young adults, as they are at high risk of developing a MDD in a short time period, and the risk increases with the number of BDP features.

Elevated inflammatory markers in women with remitted major depressive disorder and the role of early life maltreatment

Major depressive disorder (MDD) has been linked to elevated inflammation markers. It remains unclear whether the elevation of C-reactive protein (CRP) and interleukin-6 (IL-6) levels are not only observable in acute MDD but also in patients after remission. MDD is a common sequela of early life maltreatment (ELM), which has also been associated with elevated inflammation markers. While the majority of studies investigated (acute) MDD and ELM as isolated predictors of inflammation, a few studies found inflammation levels to be more pronounced in patients with MDD that were exposed to ELM. This investigation included both ELM and MDD in one study and aimed at distinguishing between the effects of MDD in remission (rMDD) and ELM and investigating potential accumulative effects on the inflammatory markers CRP and IL-6 in a population of N = 126 women (n = 122 for CRP and n = 66 for IL-6). We further investigated how disorder characteristics (course and severity) and specific types of ELM affect levels of CRP and IL-6. We found that rMDD predicted levels of CRP and IL-6 and physical abuse predicted levels of CRP when considering both predictors simultaneously, while other types of ELM did not. A later onset of MDD and a shorter time interval since the last episode were associated with higher levels of IL-6. Our findings contribute to the existing literature on the association between MDD and inflammation, suggesting that elevated levels of inflammation markers may persist even after remission of MDD. Our findings on physical abuse as a specific predictor of CRP in the presence of rMDD suggest that different types of ELM could result in distinct inflammation profiles.

No associations in preregistered study of youth depression and functional connectivity of fronto-parietal and default mode networks

Adolescence is characterized by vulnerability to the onset of major depressive disorder (MDD). The goal of this preregistered study was to assess neural correlates of depression symptoms in young adolescents, both cross-sectionally and longitudinally. The default mode network (DMN) is believed to support internal attention towards self-referential thoughts, while the fronto-parietal network (FPN) is theorized to support cognitive control and regulation of attention. As MDD diagnosis has been associated with heightened connectivity within DMN regions and diminished connectivity within FPN regions relative to healthy controls, our study builds upon group-difference analyses by using dimensional measures of depression severity. Our preregistered hypotheses were that within-DMN functional connectivity would be positively associated with concurrent depression severity, while within-FPN functional connectivity would be negatively associated with concurrent depression severity. Preregistered analyses also examined between DMN-FPN connectivity as an alternative predictor variable, and assessed the longitudinal associations between all three functional connectivity measures and change in depression severity over three subsequent waves. Multiple regression models tested cross-sectional analyses and hierarchical linear models tested longitudinal analyses. One hundred and twenty-four youth completed a resting state functional MRI. Their depression severity was assessed at the time of the scan and at three follow-up sessions. None of the predictor variables were associated with concurrent depression severity, nor with the slope of depression symptom trajectories in longitudinal analyses. These negative results add to extant cross-sectional studies, and may inform future investigations of brain correlates of depression psychopathology in youth.

Treating Postpartum Depression: What Do We Know about Brexanolone?

Postpartum depression (PPD) is defined as the onset of major depressive disorder in mothers, occurring during pregnancy or within 4 weeks post-delivery. With 7% of pregnancy-related death in the United States owing to mental health conditions, including PPD, and a global prevalence of 12%, PPD is a growing public health concern. In 2019, the Food and Drug Administration (FDA) approved brexanolone, an exogenous analog of allopregnanolone, as the first ever drug to be specifically indicated for treating patients with PPD. This approval was preceded by an open-label study and three randomized placebo-controlled trials, each assessing the safety, tolerability, and efficacy of brexanolone, using mean Hamilton Rating Scale for Depression (HAM-D) score reduction as the primary outcome. In each randomized controlled trial, the drug was administered as an intravenous infusion given over 60 h. Enrolled participants were followed up on days 7 and 30 to evaluate the sustained effect. A statistically significant reduction in mean HAM-D score compared to placebo was observed in all three studies, supporting brexanolone’s use in treating moderate-to-severe PPD. Therefore, this article attempts to briefly review the pharmacology of brexanolone, evaluate the latest available clinical data and outcomes concerning its use, reevaluate its position as a ‘breakthrough’ in managing PPD, and review the cost-related barriers to its worldwide standardized use.

Psychological factors for the onset of depression: a meta-analysis of prospective studies

ObjectivesA comprehensive overview of the evidence for factors derived from leading psychological theories of the onset of major depressive disorder (MDD) that underpin psychological interventions is scarce . We aimed...

The association between Major Depressive Disorder and premature death risk in hematologic and solid cancer: a longitudinal cohort study.

Background: the aim was to verify the association between Major Depressive Disorders (MDD) and the risk of premature death in people with oncological diseases, and to collect evidence about the causality of a possible association from a longitudinal perspective.Design and Method: it is a cohort study lasting 9 months, involving people with solid or hematologic cancers. The assessment was conducted by an ad hoc form to collect socio-demographic and clinical- oncological data, the PHQ-9 to screen MDD (cut-off ≥10) and the SF-12 to evaluate HRQoL. Relative Risk (RR) of early death between MDD exposed and not-exposed and Kaplan-Meier survival were carried out.Design and Method: it is a cohort study lasting 9 months, involving people with solid or hematologic cancers. The assessment was conducted by an ad hoc form to collect socio-demographic and clinical- oncological data, the PHQ-9 to screen MDD (cut-off ≥10) and the SF-12 to evaluate HRQoL. Relative Risk (RR) of early death between MDD exposed and not-exposed and Kaplan-Meier survival were carried out.Results: people exposed to MDD during the follow-up were 107/263 (40.7%). Among them, 36 deceased during the observation period. Overtime, having MDD and death’ occurrence showed a strong association (RR=2.15; 95% CI (1.10-4.20); χ2=5.224, p=0.0022), confirmed by Kaplan-Meier survival analysis (χ2=4.357, p=0.037). Among people who died, there was not any association between MDD, age, gender, HRQoL, cancer stage and site.Conclusions: the study confirms the association between MDD and early death in people with cancer. The absence of any association between the onset of MDD and advanced stage of cancer may suggest that it could be due to the consequences of MDD in worsening the clinical conditions related to cancer. The findings point out the relevance of MDD’ early detention among people with cancer. Significance for public health This cohort study lasting 9 months pointed out a high prevalence of Major Depressive Disorder (MDD) among people with cancer. During the time of observation, 36 deceases occurred. A strong association was observed regarding the survival rates between the MDD exposed subjects who died along the time and the MDD not exposed who survived. This association could be due to the consequences of MDD, if considering that it was not found any significant association between MDD among patients who died and a worse HRQoL when the MDD episode had been occurred, nor with age, gender, cancer stage and site. These findings point out the importance of the early detention of MDD among people with cancer, to promptly provide effective interventions for a good management of symptoms related to cancer and depression. Further studies are needed to explore the causal association between MDD and premature death in people suffering from cancer.

Sex Difference in Peripheral Inflammatory Biomarkers in Drug-Naïve Patients with Major Depression in Young Adulthood.

The number of patients with major depressive disorder (MDD) is increasing worldwide. In particular, the early onset of MDD from adolescence to young adulthood is more problematic than the later onset. The specific and expeditious identification of MDD before the occurrence of severe symptoms is significant for future interventions or therapies; however, there is no accurate diagnostic marker that has sufficient sensitivity and specificity for clinical use. In the present study, to identify the possibility of blood markers for depression, we first measured the baseline inflammatory biomarkers in the peripheral blood of 50 treatment-naïve young adults with MDD and 50 matched healthy controls. We then analyzed the correlation between prospective biomarkers and depressive symptoms using scores from various clinical depression indices. We also identified differential responses between males and females in prospective biomarkers. In young adulthood, men with MDD had increased peripheral interleukin (IL)-17 levels, whereas women with MDD had significantly increased IL-1β, IL-6, and C-reactive protein (CRP) levels compared with healthy controls. However, tumor necrosis factor-α (TNF-α), CCL1, CCL2, adiponectin, and cortisol were not significantly different in young adult individuals with MDD. Higher levels of IL-17 in the male group and of IL-1β, IL-6, and CRP in the female group may have been associated with the clinical symptoms of MDD, including depressive moods, hopelessness, suicidal ideation, low self-esteem, and reduced psychological resilience. Our findings will be useful in developing diagnostic tools or treatments for MDD in young adulthood.

Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disorder - evidence from the European Group for the Study of Resistant Depression

Despite plenty of effective antidepressant (AD) treatments, the outcome of major depressive disorder (MDD) is often unsatisfactory, probably due to improvable exploitation of available therapies. This European, cross-sectional, naturalistic multicenter study investigated the frequency of additional psychotherapy in terms of a manual-driven psychotherapy (MDP) in 1410 adult in- and outpatients with MDD, who were primarily treated with AD psychopharmacotherapy. Socio-demographic and clinical patterns were compared between patients receiving both treatments and those lacking concomitant MDP. In a total of 1279 MDD patients (90.7%) with known status of additional MDP, those undergoing a psychopharmacotherapy-MDP combination (31.2%) were younger, higher educated, more often employed and less severely ill with lower odds for suicidality as compared to patients receiving exclusively psychopharmacotherapy (68.8%). They experienced an earlier mean age of MDD onset, melancholic features, comorbid asthma and migraine and received lower daily doses of their first-line ADs. While agomelatine was more often established in these patients, MDD patients without MDP received selective serotonin reuptake inhibitors more frequently. These two patient groups did not differ in terms of response, non-response and treatment resistant depression (TRD). Accordingly, the employment of additional MDP could not be related to better treatment outcomes in MDD. The fact that MDP was applied in a minority of patients with rather beneficial socio-demographic and clinical characteristics might reflect inferior accessibility of these psychotherapeutic techniques for socially and economically disadvantaged populations.

Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank

Prevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

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.

758 Circadian rest-activity signatures in women with major depressive disorder

Abstract Introduction Patients with major depressive disorder (MDD) show disrupted circadian rhythms and sleep, including reduced daytime physical activity and poor sleep quality. However, previous findings are masked by psychotropic medication intake, co-morbid diseases and years of chronic mental illness. Here, we aim at identifying circadian motor activity patterns in unmedicated women at the onset of MDD. Methods Twelve young unmedicated women with MDD (Mean+-SD: 24.9+-5.2y; range: 18-33y) and eight age-matched healthy women (Mean+-SD: 24.5+-3.2y; range: 20-31y) participated in our study. Activity recordings were collected using wrist-worn wearable devices (actigraphs) for ~7 days in real-life settings. Cosinor analyses were performed to assess the amplitude and phase of the 24-h rest-activity activity rhythms. Non-parametric analyses were used to quantify interdaily stability and intradaily variability of the rest-activity rhythm. Furthermore, we calculated the mean activity level and scaling exponent alpha, which quantifies the temporal correlation in activity fluctuations, per 3-h bins across the 24-h sleep-wake cycle. Results Women with MDD showed a significantly higher amplitude of the 24-h rest-activity activity rhythm (Mean+-SD: 332.7+-120.8 arbitrary units) than the controls (179.7+-122.9; p=0.002), elicited by higher activity levels during the daytime (0-12h after habitual wake-up time; p&amp;lt;0.01). In contrast, women with MDD showed a trend for lower interdaily stability levels than controls (respectively, 0.41+-0.07 and 0.46+-0.08; p=0.05). Interestingly, a significant interaction effect of “group” and “time since habitual wake” was elicited for scaling exponent alpha (p&amp;lt;0.001). Accordingly, women with MDD had higher alpha values during habitual sleep (0–6 hours before habitual wake-up time) than controls (respectively, 1.18+-0.22 and 1.12+-0.22). Conclusion Unmedicated women at the onset of MDD had altered circadian motor activity patterns, as indexed by higher amplitude particularly during daytime while awake, less stable 24-h activity rhythms, and highly correlated activity patterns during sleep that closely resemble those typically occurring during wakefulness. These findings suggest that MDD per se may be associated with impaired rest-activity profiles. Ultimately, the use of wearable devices might hold important prospects for the early detection of individuals at risk for mood disorders. Support (if any) Swiss National Science Foundation Grants START #3100–055385.98, 3130-0544991.98 and 320000-108108; NIH RF1AG064312, RF1AG059867

Contributions From Resting State Functional Connectivity and Familial Risk to Early Adolescent-Onset MDD: Results From the Adolescent Brain Cognitive Development Study

Abstract Background Family history of Major Depressive Disorder (MDD) is a robust predictor of MDD onset, especially in early adolescence. We examined the relationships between familial risk for depression and alterations to resting state functional connectivity (rsFC) within the default mode network (wDMN) and between the DMN and the left/right hippocampus (DMN-LHIPP/DMN-RHIPP) to the risk for early adolescent MDD onset. Methods We examined 9403 youth aged nine to eleven from the Adolescent Brain Cognitive Development study. Depressive symptoms were measured with the parent-reported Child Behavior Checklist. Both youth and their parents completed the Kiddie Schedule for Affective Disorders and Schizophrenia, which provided MDD diagnoses. A family history screen was administered to determine familial risk for depression. Youth underwent a resting state functional magnetic resonance imaging scan, providing us with rsFC data. Results Negative wDMN rsFC was associated with child-reported current depression, both child- and parent-reported past depression, and parent-reported current depressive symptoms. No difference was found in wDMN, DMN-LHIPP or DMN-RHIPP rsFC in children with or without familial risk for depression. Familial risk for depression interacted with wDMN rsFC in association with child-reported past MDD diagnosis and parent-reported current depressive symptoms. Limitations Information such as length of depressive episodes and age of onset of depression was not collected. Conclusions Altered wDMN rsFC in youth at familial risk for depression may be associated with increased risk for MDD onset in adolescence, but longitudinal studies are needed to test this hypothesis.

Variable alterations in plasma erythropoietin and brain-derived neurotrophic factor levels in patients with major depressive disorder with and without a history of suicide attempt

It is hypothesized that major depression disorder (MDD) is associated with impaired neuronal plasticity, and that antidepressant treatments restore neuroplasticity. Brain-derived neurotrophic factor (BDNF) and erythropoietin (Epo) show neurotrophic and neuroprotective effects. We evaluated plasma Epo and BDNF levels in 50 MDD inpatients before treatment and in 50 healthy controls. The MDD inpatients consisted of 20 MDD patients without and 30 MDD patients with a recent suicide attempt. The plasma Epo level was significantly higher in nonsuicidal and suicidal MDD patients than in healthy controls (p ≤ 0.001), while the plasma BDNF level was significantly lower in suicidal MDD than in nonsuicidal MDD patients and healthy controls (p ≤ 0.001). When classifying study participants into low-Epo and high-Epo and low-BDNF and high-BDNF subgroups based on the cutoff of Epo or BDNF calculated using receiver operating characteristics (ROC) curve analysis, logistic regression analysis revealed that high-Epo and low-BDNF status correlated with a respective significant odds ratio of 7.367 (p = 0.015) and 33.123 (p ≤ 0.001) for suicidal MDD. In conclusion, plasma BDNF level was decreased in untreated MDD patients, which was presumed to be a dysfunctional effect of the onset of MDD. However, an increase in plasma Epo was observed in MDD in connection with a recent suicide attempt, indicating that this triggers hypoxic stress to induce a compensatory increase in Epo.