Outcomes In Major Depressive Disorder Research Articles

Real-world evidence from a retrospective study on suicide during depression: clinical characteristics, treatment patterns and disease burden

BackgroundSuicide stands as both a primary symptom and the direst outcome of major depressive disorder (MDD). The scarcity of effective treatment strategies makes managing MDD patients with suicide especially challenging. Hence, it is crucial to investigate disease characteristics and efficacious therapeutic strategies for these patients, drawing insights from disease databases and real-world data.MethodsIn this retrospective study, MDD patients hospitalized between January 2013 and December 2020 were investigated using Electronic Health Records (EHR) data from Beijing Anding Hospital. The study enrolled 4138 MDD patients with suicidal ideation or behavior (MDS) and 3848 without (MDNS). Demographic data, clinical attributes, treatment approaches, disease burden, and re-hospitalization within one year of discharge were extracted and compared.ResultsPatients in the MDS group were predominantly younger and female, exhibiting a higher prevalence of alcohol consumption, experiencing frequent life stress events, and having an earlier onset age. Re-hospitalizations within six months post-discharge in the MDS group were significantly higher than in the MDNS group (11.36% vs. 8.91%, p < 0.001). Moreover, a more considerable fraction of MDS patients underwent combined electroconvulsive therapy treatment (56.72% vs. 43.71%, p < 0.001). Approximately 38% of patients in both groups were prescribed two or more therapeutic regimes, and over 90% used antidepressants, either alone or combined. Selective serotonin reuptake inhibitors (SSRIs) were the predominant choice in both groups. Furthermore, antidepressants were often prescribed with antipsychotics or mood stabilizers. When medication alterations were necessary, the favoured options involved combination with antipsychotics or transitioning to alternative antidepressants. Yet, in the MDS group, following these initial modifications, the addition of mood stabilizers tended to be the more prioritized alternative.ConclusionsMDD patients with suicidal ideation or behaviour displayed distinctive demographic and clinical features. They exhibited intricate treatment patterns, a pronounced burden of illness, and an increased likelihood of relapse.

Adjunctive cariprazine for major depressive disorder: a systematic review and meta-analysis.

Converging evidence has suggested that treatment augmentation with a second-generation atypical antipsychotic (SGA) may improve treatment outcomes in major depressive disorder (MDD) patients after an incomplete response to a first-line antidepressant. Cariprazine is a recently approved SGA for MDD augmentation. Herein, we evaluate both continuous (ie, change in depressive symptom severity scores over time) and categorical (ie, remission and response rates) outcomes. Following a full-text review, four randomized controlled trials (RCTs) were included in our meta-analysis, while five studies were included for a qualitative review. Risk ratios (RRs) were calculated for all included randomized controlled studies to determine the relative response and remission rates of cariprazine compared to placebo augmentation. The RR for all-cause dropout was also determined as a proxy for overall acceptability. Two studies found a statistically significant treatment response using cariprazine augmentation. One study observed depressive symptom remission for cariprazine compared to placebo. Our random-effects model revealed moderate antidepressant effects of cariprazine, with a standardized mean difference (SMD) in Montgomery-Åsberg Depression Rating Scale (MADRS) scores of -1.79 (95% CI): -2.89, -0.69). Our pooled response RR and remission RR were calculated as 1.21 (95% CI: 1.05, 1.39, P=0.008) and 0.99 (95% CI: 0.84, 1.17, P=0.91), respectively. The RR for response was statistically significant (P<0.05). However, the RR for remission was not statistically significant. The findings from our meta-analysis include a variable magnitude of effects. Evidence suggests cariprazine may be an effective treatment for MDD; however, further results are needed to clarify this relation.

The Role of Subgenual Resting-State Connectivity Networks in Predicting Prognosis in Major Depressive Disorder

BackgroundA seminal study found higher subgenual frontal cortex resting-state connectivity with 2 left ventral frontal regions and the dorsal midbrain to predict better response to psychotherapy versus medication in individuals with treatment-naïve major depressive disorder (MDD). Here, we examined whether these subgenual networks also play a role in the pathophysiology of clinical outcomes in MDD with early treatment resistance in primary care. MethodsForty-five people with current MDD who had not responded to ≥2 serotonergic antidepressants (n = 43, meeting predefined functional magnetic resonance imaging minimum quality thresholds) were enrolled and followed over 4 months of standard care. Functional magnetic resonance imaging resting-state connectivity between the preregistered subgenual frontal cortex seed and 3 previously identified left ventromedial, ventrolateral prefrontal/insula, and dorsal midbrain regions was extracted. The clinical outcome was the percentage change on the self-reported 16-item Quick Inventory of Depressive Symptomatology. ResultsWe observed a reversal of our preregistered hypothesis in that higher resting-state connectivity between the subgenual cortex and the a priori ventrolateral prefrontal/insula region predicted favorable rather than unfavorable clinical outcomes (rs39 = −0.43, p = .006). This generalized to the sample including participants with suboptimal functional magnetic resonance imaging quality (rs43 = −0.35, p = .02). In contrast, no effects (rs39 = 0.12, rs39 = −0.01) were found for connectivity with the other 2 preregistered regions or in a whole-brain analysis (voxel-based familywise error–corrected p < .05). ConclusionsSubgenual connectivity with the ventrolateral prefrontal cortex/insula is relevant for subsequent clinical outcomes in current MDD with early treatment resistance. Its positive association with favorable outcomes could be explained primarily by psychosocial rather than the expected pharmacological changes during the follow-up period.

Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011–2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.

A distinctive subcortical functional connectivity pattern linking negative affect and treatment outcome in major depressive disorder

Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) correlation analysis to explore the association between subcortical FC and mood symptom profiles. FC score, reflecting the weighted representation of each individual in this association, was computed. Replication analysis was undertaken in an independent sample (n = 74). We also investigated the relationship between FC score and treatment outcome in the main sample. A distinctive subcortical connectivity pattern was found to be associated with negative affect. In general, higher FC between the caudate, putamen and thalamus was associated with greater negative affect. This association was partly replicated in the independent sample (similarity between the two samples: r = 0.66 for subcortical connectivity, r = 0.75 for mood symptom profile). Lower FC score predicted both remission and response to treatment after 8 weeks of antidepressant monotherapy. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical FC with negative affect. However, while the FC score significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.

Clinical features and treatment outcomes of major depressive disorder with genital symptoms.

Clinical features and treatment outcomes of major depressive disorder with genital symptoms.

Altered regional brain activity moderating the relationship between childhood trauma and depression severity

ObjectiveChildhood trauma (CT) is a major environmental risk factor for an adverse course and treatment outcome of major depressive disorder (MDD). Evidence suggests that an altered regional brain activity may play a crucial role in the relationship between CT and MDD. This study aimed to clarify the relationship between CT, regional brain activity, and depression severity. MethodsIn this study, 96 patients with MDD and 82 healthy controls (HCs) participated. Regional brain activity was measured using the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). These measures were compared between the MDD and HC groups, and the values of different brain regions were extracted as moderators. ResultsIncreased fALFF and ReHo values were observed in the left middle temporal gyrus in the MDD group compared with the HC group (p < 0.001). Furthermore, the fALFF and ReHo values moderated the positive correlation between the Childhood Trauma Questionnaire (CTQ) score, 17-item Hamilton Depression Rating Scale (HAMD-17) total score, and retardation factor score in the MDD group (all, p < 0.05). Finally, as the fALFF and ReHo values increased, the positive correlations between CTQ, HAMD-17 total, and retardation dimension scores became stronger. ConclusionOur study highlighted the crucial role of altered brain function in connecting childhood maltreatment with depressive symptoms. Our findings indicate that an altered regional brain activity could explain the potential neurobiological mechanisms of MDD symptoms, offering the opportunity to function as a powerful diagnostic biomarker.

Prediction and Validation of Hub Genes Related to Major Depressive Disorder Based on Co-expression Network Analysis.

Major depressive disorder (MDD) is generally among the most prevalent psychiatric illnesses. Significant advances have occurred in comprehension of the MDD biology. However, it is still essential to recognize new biomarkers for potential targeted treatment of patients with MDD. The present work deals with in-depth comparative computational analyses to obtain new insights, such as gene ontology and pathway enrichment analyses and weighted gene co-expression network analysis (WGCNA) through gene expression dataset. The expression of selected hub-genes was validated in MDD patients using quantitative real-time PCR (RT-qPCR). We found that MDD progression includes the turquoise module genes (p-value = 1e-18, r = 0.97). According to gene enrichment analysis, the cytokine-mediated signaling pathway mostly involves genes in this module. By selection of four candidate hub-genes (IL6, NRG1, TNF, and BDNF), RT-qPCR validation was performed. A significant NRG1 downregulation was revealed by the RT-qPCR outcomes in MDD. In MDD patients, TNF and IL6 expression were considerably higher, and no considerable differences were found in the BDNF expression. Ultimately, based on ROC analyses, IL6, NRG1, and TNF had a higher MDD diagnostic performance. Therefore, our study presents information on the intricate association between MDD development and cytokine-mediated signaling, thus providing new rationales to develop new therapeutic approaches.

Care pathways, prescribing practices and treatment outcomes in major depressive disorder and treatment-resistant depression: retrospective, population-based cohort study.

Despite the availability of effective therapies, many patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD). To evaluate and compare prescribing patterns, contact with specialist services and treatment outcomes in patients with MDD and TRD. This was a retrospective analysis of linked primary and secondary care National Health Service data in the north-west London Discover-NOW data-set. Eligible patients were adults who had diagnostic codes for depression and had been prescribed at least one antidepressant between 2015 and 2020. A total of 110 406 patients were included, comprising 101 333 (92%) with MDD and 9073 (8%) with TRD. Patients with TRD had significantly higher risks of suicidal behaviour and comorbidities such as anxiety, asthma, and alcohol or substance misuse (all P < 0.0001). Citalopram, sertraline, fluoxetine and mirtazapine accounted for 83% of MDD and 71% of TRD prescriptions. Use of antidepressant switching (1% MDD, 7% TRD) and combination therapy (1%, 5%) was rare, whereas augmentation occurred more frequently in the TRD group (4%, 35%). Remission was recorded in 42 348 (42%) patients with MDD and 1188 (13%) with TRD (P < 0.0001), whereas relapse was seen in 20 970 (21%) and 4923 (54%), respectively (P < 0.0001). Mean times from diagnosis to first contact with mental health services were 38.9 (s.d. 33.6) months for MDD and 41.5 (s.d. 32.0) months for TRD (P < 0.0001). There appears to be a considerable difference between treatment guidelines for depression and TRD and the reality of clinical practice. Long-term treatment with single antidepressants, poor remission, and high relapse rates among patients in primary care highlight the need to optimise treatment pathways and access to newer therapies.

Polygenic scores of subcortical brain volumes as possible modulators of treatment response in depression

A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly hippocampal volume, as potential predictors of treatment response, as well as genetic factors.This study investigated the association of polygenic scores (PGSs) for seven subcortical brain volumes (including the hippocampus, nucleus accumbens, amygdala, and caudate nucleus) with treatment non-response and non-remission in MDD.Patients with MDD were recruited in the context of five clinical studies, including a total of 3637 individuals. PGSs were estimated using a Bayesian framework and continuous shrinkage priors (PRS-CS-auto) after standard genotype quality control and imputation. Logistic regressions were performed between PGSs and non-response or non-remission in each sample, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, using a random-effect model.No association was significant in the meta-analysis after Bonferroni correction. The top finding was found for the caudate volume PGS and non-remission (OR = 1.09, 95% CI = 1.01–1.19, p = 0.036), with no evidence of heterogeneity. Leave-one-out sensitivity analyses showed that this result was influenced by the two largest samples in the meta-analysis.This result should be considered as preliminary as it did not reach the Bonferroni-adjusted significance threshold. Future studies with greater statistical power may enhance the predictive performance of PGSs and contribute to the identification of polygenic predictors of treatment outcomes in MDD, contributing to precision psychiatry.

Alpha peak frequency-based Brainmarker-I as a method to stratify to pharmacotherapy and brain stimulation treatments in depression

Biomarkers predicting treatment outcome in major depressive disorder could enhance clinical improvement. Here this observational and prospective accuracy study investigates whether an age- and sex-normalized electroencephalography biomarker, based on the individual alpha frequency (iAF), can successfully stratify patients to different interventions such as repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). Differential iAF directions were explored for sertraline, as well as rTMS (N = 196) and ECT (N = 41). A blinded out-of-sample validation (EMBARC; N = 240) replicated the previously found association between low iAF and better sertraline response. The subgroup of patients with an iAF around 10 Hz had a higher remission rate following 10 Hz rTMS compared with the group level, while the high-iAF subgroup had highest remission to 1 Hz rTMS and the low-iAF subgroup to ECT. Blinded out-of-sample validations for 1 Hz (N = 39) and ECT (N = 51) corroborated these findings. The present study suggests a clinically actionable electroencephalography biomarker that can successfully stratify between various antidepressant treatments.

The Intersection of Insomnia Disorder and Major Depressive Disorder: A Clinical Perspective

Major depressive disorder (MDD) is associated with profound sleep architectural alterations including reduced slow wave activity, increased delta sleep ratio, REM sleep disinhibition, shortened REM onset latency, and increased REM density. Antidepressants, though mitigating depressive symptoms, often disrupt sleep patterns, highlighting the delicate balance between treatment benefits and sleep-related impacts. Comprehensive assessment and management of insomnia is pivotal due to its significant implications for effective clinical management and treatment outcomes in MDD. Nonpharmacological treatments, notably cognitive-behavioral therapy for insomnia (CBTi), and digital CBTi (dCBTi) should be considered. CBTi unravels maladaptive sleep beliefs and behaviors, yielding improvements in both insomnia and MDD symptoms. Digital CBTi platforms extend accessibility, offering potential relief to a broader demographic. Sedating antidepressants, nonbenzodiazepine hypnotics, and atypical antipsychotics address insomnia within MDD, with cautious consideration for side effects. A combination of pharmacotherapy with CBTi might yield augmented outcomes in patients with MDD and comorbid insomnia. Ketamine, electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagal nerve stimulation (VNS), and deep brain stimulation (DBS) explore novel dimensions in treating treatment-resistant depression, potentially influencing sleep disruptions. [ Psychiatr Ann . 2023;53(11):502–507.]

Altered neural activity in the reward-related circuit associated with anhedonia in mild to moderate Major Depressive Disorder

BackgroundAnhedonia is a significant predictor of disease progression and treatment outcomes in Major Depressive Disorder (MDD), linked to reward network dysfunctions. However, understanding of its underlying neural mechanisms remains limited. This study aimed to investigate the brain functional mechanisms underlying MDD with anhedonia using resting-state functional magnetic resonance imaging (rs-fMRI). MethodsThe Snaith-Hamilton Pleasure Scale (SHAPS) was used to evaluation MDD with anhedonia (anMDD) and non-anhedonia MDD (non-anMDD). Forty-eight patients with anMDD, Forty-four patients with non-anMDD, and Fifty healthy controls (HCs) were enrolled for the fMRI scans. A seed-based functional connectivity (FC) method was employed to explore reward network abnormalities. ResultsanMDD patients exhibited lower FC values in Ventral Striatum (VS), right lateral Ventral Tegmental Area (VTA_R), left Thalamus (THA_L), and higher FC values in Ventromedial Prefrontal Cortex (vmPFC), left Anterior Insula (AI_L), and Presupplementary Motor Area (Pre-SMA) compared to HCs. Comparing anMDD to non-anMDD, significant differences were observed in FC values of VS, vmPFC, Pre-SMA, and THA_L regions. Correlation analysis revealed positive correlations between FC values of VS_R and NAc_R, as well as THA_L and Cerebellum_Crus1_L, with SHAPS scores. Negative correlations were observed between FC values of Pre-SMA and the right caudate, and between vmPFC and Frontal_Mid_Orb_L, and SHAPS scores. ConclusionBoth anMDD and non-anMDD groups demonstrated abnormal FCs in the reward network. These findings indicate distinct roles of reward-related circuits in the two subtypes, contributing to a refined understanding of depression phenotypes and potential directions for targeted interventions.

Patient characteristics, validity of clinical diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D): design, procedures and outcomes

BackgroundSuicidality, ranging from passive suicidal thoughts to suicide attempt, is common in major depressive disorder (MDD). However, relatively little is known about patient, illness and treatment characteristics in those with co-occurring MDD and suicidality, including the timing of and factors associated with the offset, continuation or reemergence of suicidality. Here, we present the background, rationale, design and hypotheses of the Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D) study, an investigator-initiated, observational study, funded by Janssen-Cilag GmbH.Methods/ResultsOASIS-D is an eight-site, six-month, cohort study of patients aged 18-75 hospitalized with MDD. Divided into three sub-studies and patient populations (PPs), OASIS-D will (i) systematically characterize approximately 4500 consecutively hospitalized patients with any form of unipolar depressive episode (PP1), (ii) evaluate the validity of the clinical diagnosis of moderate or severe unipolar depressive episode with the Mini-International Neuropsychiatric Interview (M.I.N.I.) and present suicidality (at least passive suicidal thoughts) present ≥ 48 h after admission with the Sheehan-Suicide Tracking Scale (S-STS), assessing also predictors of the diagnostic concordance/discordance of MDD in around 500 inpatients (PP2), and (iii) characterize and prospectively follow for 6 months 315 inpatients with a research-verified moderate or severe unipolar depressive episode and at least passive suicidal thoughts ≥ 48 h after admission, evaluating treatment and illness/response patterns at baseline, hospital discharge, 3 and 6 months. Exploratory objectives will describe the association between the number of days with suicidality and utilization of outpatient and inpatient care services, and structured assessments of factors influencing the risk of self-injurious behavior without suicidal intent, and of continuous, intermittent or remitted suicidality during the 6-month observation period.ConclusionDespite their frequency and clinical relevance, relatively little is known about patient and treatment characteristics of individuals with MDD and suicidality, including factors moderating and mediating the outcome of both MDD and suicidality. Results of the OASIS-D study are hoped to improve the understanding of the frequency, correlates and 6-month naturalistic treatment and outcome trajectories of different levels of suicidality in hospitalized adults with MDD and suicidality.Trial registrationNCT04404309 [ClinicalTrials.gov]

Estimates of Major Depressive Disorder and Treatment Among Adolescents by Race and Ethnicity

The COVID-19 pandemic has contributed to poorer mental health and a greater need for treatment. Nationally representative estimates of major depressive disorder (MDD) and mental health treatment among US adolescents during the pandemic are needed. To estimate MDD prevalence among adolescents, evaluate mental health treatment use among adolescents with MDD, and assess differences by race and ethnicity. This cross-sectional analysis of the nationally representative 2021 National Survey on Drug Use and Health included noninstitutionalized US adolescents between the ages of 12 and 17 years (n = 10 743). Analytic weights were applied to all rates and model estimates to be nationally representative and account for sample design and survey nonresponse. Data were collected from January 14 to December 20, 2021, and analyzed from February 11 to April 3, 2023. Self-reported race and ethnicity. Dichotomous outcomes of MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition), MDD-specific mental health treatment, any type of mental health treatment, telehealth visits, and delays in mental health treatment. The sample included 10 743 adolescents (51.1% male). Self-reported race and ethnicity included 5.1% Asian, 14.1% Black, 23.3% Latinx, 51.2% White, and 6.3% more than 1 race. Ages were evenly distributed: 34.0% aged 12 to 13 years; 33.3% aged 14 to 15 years; and 32.7% aged 16 to 17 years. Adolescents of more than 1 race or ethnicity had the highest MDD rate (26.5%). Compared with White adolescents, the lowest rates of any MDD treatment overall were found among Latinx adolescents (29.2% [95% CI, 22.2%-36.2%]) and those of more than 1 race or ethnicity (21.1% [95% CI, 11.6%-30.7%]). Similar results were found for treatment by any clinician (Latinx, 25.6% [95% CI, 18.8%-32.4%]; >1 race or ethnicity, 19.1% [95% CI, 9.7%-28.6%]), treatment by a mental health specialist (Latinx, 22.9% [95% CI, 16.9%-28.9%]; >1 race or ethnicity, 16.7% [95% CI, 7.1%-26.3%]), treatment by a nonspecialist clinician (Latinx, 7.3% [95% CI, 3.3%-11.3%]; >1 race or ethnicity, 4.8% [95% CI, 1.9%-7.7%]), and use of any psychotropic medication prescription (Latinx, 11.6% [95% CI, 7.3%-15.9%]; >1 race or ethnicity, 8.3% [95% CI, 2.8%-13.7]). Compared with White adolescents, Black adolescents had lower rates of MDD treatment by any clinician (31.7% [95% CI, 23.7%-39.8%]) and by nonspecialist clinicians (8.4% [95% CI, 3.8%-13.2%]) and experienced lower prescription rates for any psychotropic medication (12.6 [95% CI, 4.6%-20.6%]). Asian (16.0% [95% CI, 5.0%-27.2%]) and Latinx (17.8% [95% CI, 12.6%-23.0%]) adolescents had lower rates of virtual mental health treatment compared with White adolescents. Black (19.1% [95% CI, 14.1%-24.2%]) and Latinx (17.9% [95% CI, 15.0%-21.1%]) adolescents had lower rates of appointments transition to telehealth, while Black adolescents (14.1% [95% CI, 10.7%-17.4%]) experienced delays getting their prescriptions. During the first full calendar year of the pandemic, approximately 1 in 5 adolescents had MDD, and less than half of adolescents who needed treatment had any mental health treatment. Adolescents in racial and ethnic minority groups, particularly Latinx, experienced the lowest treatment rates. Federal policy should target adolescents as a whole, and minority populations in particular, to ensure equitable treatment access. Efforts should consider the social, racial, ethnic, and cultural determinants of health.

Prediction of Treatment Outcome in Major Depressive Disorder Using Ensemble of Hybrid Transfer Learning and Long Short-Term Memory Based on EEG Signal

Major Depressive Disorder (MDD) is a widespread global mental disease. The Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) antidepressants prescribed for MDD patients is limited and pre-treatment assessment of treatment outcome is a vital task. In this study, a hybrid model based on Transfer Learning (TL) of powerful pre-trained deep Convolutional Neural Networks (CNNs) empowered with bidirectional Long Short-term Memory (BLSTM) cells and attention mechanism were developed to classify Responders (R) and Non-Responders (NR) to SSRI antidepressants, using raw data images of pre-treatment EEG signal obtained from 30 MDD patients. TL-LSTM-Attention models based on VGG16, Xception, and Densenet121 models were created for the classification of R/NR. Results show that the highest performance of hybrid TL-LSTM-Attention models was achieved by VGG16-LSTM-Attention with an accuracy of 98.21%, sensitivity of 96.22%, and specificity of 99.67%. An Ensemble model based on weighted majority voting among hybrid models is constructed to surpass the performance of each single hybrid model. Our proposed ensemble model gained accuracy, sensitivity, and specificity of 98.84%, 97.80%, and 99.60%, respectively. Hence, the proposed model which is an ensemble of TL-LSTM-Attention models fed by raw data images of EEG signal leads to high confidence in the prediction of antidepressants treatment outcome.

Exome-wide association study of treatment-resistant depression suggests novel treatment targets

Treatment-resistant depression (TRD) is a severe form of major depressive disorder (MDD) with substantial public health impact and poor treatment outcome. Treatment outcome in MDD is significantly heritable, but genome-wide association studies have failed to identify replicable common marker alleles, suggesting a potential role for uncommon variants. Here we investigated the hypothesis that uncommon, putatively functional genetic variants are associated with TRD. Whole-exome sequencing data was obtained from 182 TRD cases and 2021 psychiatrically healthy controls. After quality control, the remaining 149 TRD cases and 1976 controls were analyzed with tests designed to detect excess burdens of uncommon variants. At the gene level, 5 genes, ZNF248, PRKRA, PYHIN1, SLC7A8, and STK19 each carried exome-wide significant excess burdens of variants in TRD cases (q < 0.05). Analysis of 41 pre-selected gene sets suggested an excess of uncommon, functional variants among genes involved in lithium response. Among the genes identified in previous TRD studies, ZDHHC3 was also significant in this sample after multiple test correction. ZNF248 and STK19 are involved in transcriptional regulation, PHYIN1 and PRKRA are involved in immune response, SLC7A8 is associated with thyroid hormone transporter activity, and ZDHHC3 regulates synaptic clustering of GABA and glutamate receptors. These results implicate uncommon, functional alleles in TRD and suggest promising novel targets for future research.

Treatment outcomes in major depressive disorder in patients with comorbid alcohol use disorder: A STAR*D analysis

IntroductionGuidance on Major Depressive Disorder (MDD) treatment in those with comorbid Alcohol Use Disorder (AUD) is limited. We performed a secondary analysis on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, examining the association between comorbid AUD and depression outcomes. MethodsSTAR*D was a real-world effectiveness trial starting with citalopram in level 1. Non-responding participants progressed through 3 other sequential treatment levels with different switch or augmentation options. Antidepressant outcomes were compared between MDD (n = 2826) and comorbid MDD and AUD (n = 864). Logistic regressions were performed to evaluate remission and response predictors in the total STAR*D sample and the AUD-comorbidity interaction. ResultsChi-squared tests showed no significant difference in response or remission rates from depression between groups across treatment levels. Higher Hamilton Rating Scale for Depression (HRSD) score was associated with overall lower odds of remission in treatment level 1 (OR = 0.93, p < 0.001) and 2 (OR = 0.95, p < 0.001), with no significant interaction with comorbid AUD. Higher baseline suicidality had overall lower odds of remission in level 1 (OR = 0.82, p < 0.001) and 2 (OR = 0.1, p < 0.001), but with comorbid AUD compared to no AUD, suicidality increased odds of level 1 remission (OR = 1.30, p = 0.012). In comorbid AUD in level 2, venlafaxine was associated with lower odds of remission (OR = 0.13, p = 0.013) and response (OR = 0.12, p = 0.006); bupropion with lower odds of response (OR = 0.22, p = 0.024). LimitationsOpen label study design and lack of alcohol use data. ConclusionsComorbid AUD may interact with predictors of antidepressant response in MDD and using venlafaxine or bupropion may be less effective. Addressing this comorbidity requires unique assessment and treatment approaches.

Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II)

PurposeTo assess the effect of esketamine nasal spray on patient-reported outcomes (PROs) in patients with major depressive disorder having active suicidal ideation with intent (MDSI).MethodsPatient-level data from two phase 3 studies (ASPIRE I; ASPIRE II) of esketamine + standard of care (SOC) in patients (aged 18–64 years) with MDSI, were pooled. PROs were evaluated from baseline through end of the double-blind treatment phase (day 25). Outcome assessments included: Beck Hopelessness Scale (BHS), Quality of Life (QoL) in Depression Scale (QLDS), European QoL Group-5-Dimension-5-Level (EQ-5D-5L), and 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Changes in BHS and QLDS scores (baseline to day 25) were analyzed using a mixed-effects model for repeated measures (MMRM).ResultsPooled data for esketamine + SOC (n = 226; mean age: 40.5 years, 59.3% females) and placebo + SOC (n = 225; mean age: 39.6 years, 62.2% females) were analyzed. Mean ± SD change from baseline to day 25, esketamine + SOC vs placebo + SOC (least-square mean difference [95% CI] based on MMRM): BHS total score, − 7.4 ± 6.7 vs − 6.8 ± 6.5 [− 1.0 (− 2.23, 0.21)]; QLDS score, − 14.4 ± 11.5 vs − 12.2 ± 10.8 [− 3.1 (− 5.21, − 1.02)]. Relative risk (95% CI) of reporting perceived problems (slight to extreme) in EQ-5D-5L dimensions (day 25) in esketamine + SOC vs placebo + SOC: mobility [0.78 (0.50, 1.20)], self-care [0.83 (0.55, 1.27)], usual activities [0.87 (0.72, 1.05)], pain/discomfort [0.85 (0.69, 1.04)], and anxiety/depression [0.90 (0.80, 1.00)]. Mean ± SD changes from baseline in esketamine + SOC vs placebo + SOC for health status index: 0.23 ± 0.21 vs 0.19 ± 0.22; and for EQ-Visual Analogue Scale: 24.0 ± 27.2 vs 19.3 ± 24.4. At day 25, mean ± SD in domains of TSQM-9 scores in esketamine + SOC vs placebo + SOC were: effectiveness, 67.2 ± 25.3 vs 56.2 ± 26.8; global satisfaction, 69.9 ± 25.2 vs 56.3 ± 27.8; and convenience, 74.0 ± 19.4 vs 75.4 ± 18.7.ConclusionThese PRO data support the patient perspective of the effect associated with esketamine + SOC in improving health-related QoL in patients with MDSI.Trial registration: ClinicalTrials.gov Identifier: ASPIRE I, NCT03039192 (Registration date: February 1, 2017); ASPIRE II, NCT03097133 (Registration date: March 31, 2017).

Comparison of behavioral activation-enhanced cognitive processing therapy and cognitive processing therapy among U.S. service members: A randomized clinical trial

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) frequently co-occur and can cause significant impairment. Data are lacking as to whether interventions targeting both PTSD and MDD may improve treatment outcomes among individuals with this comorbidity compared with existing evidence-based PTSD treatments alone. This randomized trial compared the effectiveness of cognitive processing therapy (CPT) enhanced with behavioral activation (BA+CPT) versus CPT among 94 service members (52 women and 42 men; age M = 28.5 years) with comorbid PTSD and MDD. The primary outcome was clinician-administered depression symptom severity on the Montgomery-Åsberg Depression Rating Scale (MADRS) from pretreatment through 3-month follow-up. Intent-to-treat analyses using multilevel models showed statistically and clinically significant decreases in MADRS scores for both conditions over time, with no significant differences between BA+CPT and CPT. Secondary depression and PTSD symptom outcomes followed a similar pattern of results. For diagnostic MDD and PTSD outcomes using available data, no statistically significant differences between treatments emerged at posttreatment or 3-month follow-up. Sessions attended, dropout rate, and treatment satisfaction did not significantly differ between treatments. Outcomes were comparable for both treatments, suggesting that BA+CPT and CPT were similarly effective psychotherapy options for comorbid PTSD and MDD.