Depressive Symptoms In Major Depressive Disorder Research Articles

Understanding of Depressive Symptomatology across Major Depressive Disorder and Bipolar Disorder: A Network Analysis.

Background and Objectives: Depressive symptoms are prominent in both major depressive disorder (MDD) and bipolar disorder (BD). However, comparative research on the network structure of depressive symptoms in these two diagnostic groups has been limited. This study aims to compare the network structure of depressive symptoms in MDD and BD, providing a deeper understanding of the depressive symptomatology of each disorder. Materials and Methods: The Zung Self-Rating Depressive Scale, a 20-item questionnaire, was administered to assess the depressive symptoms in individuals with MDD (n = 322) and BD (n = 516). A network analysis was conducted using exploratory graph analysis (EGA), and the network structure was analyzed using regularized partial correlation models. To validate the dimensionality of the Zung SDS, principal component analysis (PCA) was adopted. Centrality measures of the depressive symptoms within each group were assessed, followed by a network comparison test between the two groups. Results: In both diagnostic groups, the network analysis revealed four distinct categories, aligning closely with the PCA results. "Depressed affect" emerged as the most central symptom in both MDD and BD. Furthermore, non-core symptoms, "Personal devaluation" in MDD and "Confusion" in BD, displayed strong centrality. The network comparison test did not reveal significant differences in the network structure between MDD and BD. Conclusions: The absence of significant differences in the network structures between MDD and BD suggests that the underlying mechanisms of depressive symptoms may be similar across these disorders. The identified central symptoms, including "Depressed affect", in both disorders and the distinct non-core symptoms in each highlight the complexity of the depressive symptomatology. Future research should focus on validating these symptoms as therapeutic targets and incorporate various methodologies, including non-metric dimension reduction techniques or canonical analysis.

Distorted thoughts as a mediator of depressive symptoms in patients with major depressive disorder: a longitudinal study

BackgroundDistorted thoughts are common in Major Depressive Disorder (MDD), and can impact patients’ perceptions of depression severity, and predict chronicity and treatment response. This study aimed to investigate whether distorted thoughts mediate depressive symptoms in MDD over a 6-month period.MethodThese are secondary results from a study that followed 119 patients diagnosed with moderate to severe MDD for 6 months. Diagnoses were confirmed by the Structured Interview for DSM-IV (SCID-CV). The analysis was composed of results from the Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), the second edition of the Beck Depression Inventory (BDI-II), and the Depression Thoughts Scale (DTS) collected at weeks 1, 8, 12 and 24.ResultsResults showed that the DTS mediated the relationship between depressive symptoms experienced approximately 3 months after starting antidepressant treatment.ConclusionCognitive distortions were linked as a mediator to depressive symptoms, highlighting the importance of early psychological interventions in patients with MDD who exhibit these distortions.Trial registrationNCT02268487.

Disrupted functional connectivity of the cerebellum with default mode and frontoparietal networks in young adults with major depressive disorder

Cerebellar dysconnectivity has repeatedly been documented in major depressive disorder (MDD). The cerebellum is composed of multiple functionally distinct subunits, and whether those subunits show similar or distinct dysconnectivity patterns with the cerebrum in MDD, is still unclear and needs to be further clarified. In this study, 91 MDD patients (23 male and 68 female) and 59 demographically matched healthy controls (22 male and 37 female) were enrolled to explore the cerebellar-cerebral dysconnectivity pattern in MDD by using the cutting-edge cerebellar partition atlas. Results showed that MDD patients exhibit decreased cerebellar connectivity with cerebral regions of default mode (DMN), frontoparietal networks (FPN), and visual areas. The dysconnectivity pattern was statistically similar across cerebellar subunits, with no significant diagnosis-by-subunit interactions. Correlation analyzes showed that cerebellar-dorsal lateral prefrontal cortex (DLPFC) connectivity is significantly correlated with anhedonia in MDD patients. Such dysconnectivity pattern was not affected by sex, which, however, should be further replicated in larger samples. These findings suggest a generalized disrupted cerebellar-cerebral connectivity pattern in MDD across all cerebellar subunits, which partially accounts for depressive symptoms in MDD, thus highlighting the pivotal role of the disrupted connectivity of cerebellum with DMN and FPN in the neuropathology of depression.

Gyrification patterns in first-episode, drug-naïve major depression: Associations with plasma levels of brain-derived neurotrophic factor and psychiatric symptoms.

Cortical structural changes in major depressive disorder (MDD) are usually studied using a voxel-based morphometry approach to delineate the cortical gray matter volume. Among cortical structures, gyrification patterns are considered a relatively stable indicator. In this study, we investigated differences in gyrification patterns between MDD patients and healthy controls (HCs) and explored the association of gyrification patterns with plasma brain-derived neurotrophic factor (BDNF) levels and depressive symptoms in MDD patients. We evaluated 79 MDD patients and 94 HCs and assessed depression severity in the patients using the 17-item Hamilton Depression Rating Scale (HAM-D). Blood samples of both groups were collected to measure plasma BDNF levels. Magnetic resonance imaging (MRI) data were obtained using three-dimensional fast-spoiled gradient-recalled acquisition. Differences in plasma BDNF levels between groups were examined using the Mann-Whitney U test. Principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted to investigate the gyrification patterns which were significantly different between the groups, i.e., those with variable importance in projection (VIP) scores of >1.5 and p-value < 0.05 in multiple regression analyses adjusted for age and sex. Finally, multiple regression analysis was performed on the selected gyrification patterns to examine their association with BDNF levels in the two groups and HAM-D in the patients. There were no significant differences in plasma BDNF levels between the groups. We found that 108 (71.0%) of 152 total local gyrification indices were MDD < HC. We identified 10 disease-differentiating factors based on critical gyrification features (VIP > 1.5 and p-value adjusted for age and sex < 0.05). However, we found no significant correlations between the 10 gyrification patterns and plasma BDNF levels and no interaction with group. Moreover, no significant correlations were observed between the local gyrification indices and HAM-D total scores. These results suggest that abnormal early cortical neurodevelopment may mediate vulnerability to MDD, independent of plasma BDNF levels and depressive symptoms.

Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder

BackgroundUnderstanding the neurobiology underlying bipolar disorder (BD) versus major depressive disorder (MDD) is crucial for accurate diagnosis and for driving the discovery of novel treatments. A promising target is the metabotropic glutamate receptor 5 (mGluR5), a modulator of glutamate transmission associated with synaptic plasticity. We measured mGluR5 availability in individuals with MDD and BD for the first time using positron emission tomography. MethodsIndividuals with BD (n = 17 depressed; n = 10 euthymic) or MDD (n = 17) and healthy control (HC) individuals (n = 18) underwent imaging with [18F]FPEB positron emission tomography to quantify mGluR5 availability in regions of the prefrontal cortex, which was compared across groups and assessed in relation to depressive symptoms and cognitive function. ResultsPrefrontal cortex mGluR5 availability was significantly different across groups (F6,116 = 2.18, p = .050). Specifically, mGluR5 was lower in BD versus MDD and HC groups, with no difference between MDD and HC groups. Furthermore, after dividing the BD group, mGluR5 was lower in both BD-depression and BD-euthymia groups versus both MDD and HC groups across regions of interest. Interestingly, lower dorsolateral prefrontal cortex mGluR5 was associated with worse depression in MDD (r = −0.67, p = .005) but not in BD. Significant negative correlations were observed between mGluR5 and working memory in MDD and BD-depression groups. ConclusionsThis work suggests that mGluR5 could be helpful in distinguishing BD and MDD as a possible treatment target for depressive symptoms in MDD and for cognitive alterations in both disorders. Further work is needed to confirm differentiating roles for mGluR5 in BD and MDD and to probe modulation of mGluR5 as a preventive/treatment strategy.

Differential Diagnosis of Major Depressive Disorder and Bipolar Disorder: Genetic and Hormonal Assessment and the Influence of Early-Life Stress.

Few studies have assessed biomarkers for the differentiation of major depressive disorder (MDD) and bipolar disorder (BD). However, some elements of depression such as hormones and receptors of the renin-angiotensin-adrenal system (RAAS), the hypothalamus-pituitary-adrenal (HPA) axis, and history of early-life stress (ELS) could be considered for differential diagnosis. Therefore, this study aimed to assess aldosterone and cortisol levels, MR and GR gene polymorphisms, and ELS as potential biomarkers for differentiating MDD and BD. This study presents a case-control design. Groups comprised samples for genetic, cortisol, and aldosterone analysis: healthy control (HC; n = 113/97/103), MDD (n = 78/69/67) and BD (n = 82/68/65) subjects. Furthermore, all subjects were assessed for diagnostic screening, the severity of depression, and history of ELS by applying MINI-PLUS, GRID-HDRS, and CTQ, respectively. In addition, genotype and allelic frequencies of GR (N363S, R22/23K and BclI) and MR (MI180V and -2G/C) polymorphisms were evaluated via PCR. Our findings demonstrate that basal aldosterone levels may be a biomarker for differentiating BD and MDD. Furthermore, ELS affects the HPA axis in BD, cortisol may be considered a biomarker for distinguishing BD and MDD, but only in the absence of ELS, and, finally, history of ELS and MR-2G/C variant alleles are factors that contribute to the severity of depressive symptoms in MDD and BD.

The role of leptin in indirectly mediating "somatic anxiety" symptoms in major depressive disorder.

BackgroundLeptin is a multifunctional hormone secreted from adipose tissue, which plays a core role in regulating energy intake and expenditure. Evidence has demonstrated that leptin receptors are located in brain areas involved in emotional processing, and major depressive disorder (MDD) is characterized by dysfunction of emotional processing. Taken together, these features suggest that leptin may play a potential role in the pathophysiology of MDD. However, the precise roles of leptin in modulating depressive symptoms in MDD remain unclear.MethodsParticipants [18 drug-naïve MDD patients, 15 unaffected first-degree relatives of MDD patients (FDR-MDD), and 40 healthy controls] completed clinical assessments and provided blood samples for measurement of leptin levels. We evaluated the effect of leptin on clinical status (MDD or FDR-MDD) and symptomatic dimensionalities of MDD using mediation analysis.ResultsWe found that leptin was increased in MDD patients and this only predicted “somatic anxiety” symptoms. Furthermore, leptin was a significant and indirect mediator of the association between clinical status (MDD or FDR-MDD) and “somatic anxiety” symptoms.ConclusionOur finding that leptin was a significant and indirect mediator of clinical status (MDD or FDR-MDD) and “somatic anxiety” symptoms suggests that leptin may indirectly affect somatic depressive symptoms in MDD. Our findings may provide a theoretical basis for novel clinical interventions in MDD.

A transdiagnostic meta-analysis of physical and social Anhedonia in major depressive disorder and schizophrenia spectrum disorders

Introduction: Anhedonia is a transdiagnostic construct conceptualized as physical or social, however, the extent to which these subtypes differ across psychotic and mood pathology remains poorly understood. We aimed to quantify the severity of physical and social anhedonia across Major Depressive Disorder (MDD) and Schizophrenia Spectrum Disorder (SSDs).Methods: We conducted meta-analyses of the Chapman Physical and Social Anhedonia Scales (PAS;SAS). We reviewed data from participants with MDD, and SSDs separately.Results: Our first meta-analysis (n = 8 studies, 409 participants) with MDD revealed elevated SAS and PAS in MDD compared to controls. Within-group differences were not significant. Depressive symptom severity moderated the between-group effect of PAS. Our second meta-analysis (n = 44 studies, 3352 participants) revealed elevated SAS and PAS in SSDs compared to controls. We detected a moderate difference between the SAS and PAS within the SSD group. Age moderated within-group differences of SAS and PAS.Discussion: People with SSD or MDD experience elevated SAS and PAS compared to controls. People with SSDs endorse greater challenges experiencing social rewards relative to physical rewards. People with MDD experience social and physical rewards similarly. The moderating role of depressive symptoms in MDD suggests that physical anhedonia is more state-like than social anhedonia.

Dysregulation of mitochondrial dynamics, mitophagy and apoptosis in major depressive disorder: Does inflammation play a role?

Recent studies have suggested that mitochondrial dysfunction and dysregulated neuroinflammatory pathways are involved in the pathophysiology of major depressive disorder (MDD). Here, we aimed to assess the differences in markers of mitochondrial dynamics, mitophagy, general autophagy, and apoptosis in peripheral blood mononuclear cells (PBMCs) of MDD patients (n = 77) and healthy controls (HCs, n = 24). Moreover, we studied inflammation engagement as a moderator of mitochondria dysfunctions on the severity of depressive symptoms. We found increased levels of Mfn-2 (p < 0.001), short Opa-1 (S-Opa-1) (p < 0.001) and Fis-1 (p < 0.001) in MDD patients, suggesting an increase in the mitochondrial fragmentation. We also found that MDD patients had higher levels of Pink-1 (p < 0.001), p62/SQSTM1 (p < 0.001), LC3B (p = 0.002), and caspase-3 active (p = 0.001), and lower levels of parkin (p < 0.001) compared with HCs. Moreover, we showed that that MDD patients with higher CRP levels had higher levels of Mfn-2 (p = 0.001) and LC3B (p = 0.002) when compared with MDD patients with low CRP. Another notable finding was that the severity of depressive symptoms in MDD is associated with changes in protein levels in pathways related to mitochondrial dynamics and mitophagy, and can be dependent on the inflammatory status. Overall, our study demonstrated that a disruption in the mitochondrial dynamics network could initiate a cascade of abnormal changes relevant to the critical pathological changes during the course of MDD and lead to poor outcomes.

Common Brain Networks Between Major Depressive-Disorder Diagnosis and Symptoms of Depression That Are Validated for Independent Cohorts.

Large-scale neuroimaging data acquired and shared by multiple institutions are essential to advance neuroscientific understanding of pathophysiological mechanisms in psychiatric disorders, such as major depressive disorder (MDD). About 75% of studies that have applied machine learning technique to neuroimaging have been based on diagnoses by clinicians. However, an increasing number of studies have highlighted the difficulty in finding a clear association between existing clinical diagnostic categories and neurobiological abnormalities. Here, using resting-state functional magnetic resonance imaging, we determined and validated resting-state functional connectivity related to depression symptoms that were thought to be directly related to neurobiological abnormalities. We then compared the resting-state functional connectivity related to depression symptoms with that related to depression diagnosis that we recently identified. In particular, for the discovery dataset with 477 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a brain network prediction model of depression symptoms (Beck Depression Inventory-II [BDI] score). The prediction model significantly predicted BDI score for an independent validation dataset with 439 participants from 4 different imaging sites. Finally, we found 3 common functional connections between those related to depression symptoms and those related to MDD diagnosis. These findings contribute to a deeper understanding of the neural circuitry of depressive symptoms in MDD, a hetero-symptomatic population, revealing the neural basis of MDD.

Disrupted Structural Brain Network Organization Behind Depressive Symptoms in Major Depressive Disorder.

Major depressive disorder (MDD) is a severe and devastating condition. However, the anatomical basis behind the affective symptoms, cognitive symptoms, and somatic-vegetative symptoms of MDD is still unknown. To explore the mechanism behind the depressive symptoms in MDD, we used diffusion tensor imaging (DTI)–based structural brain connectivity analysis to investigate the network difference between MDD patients and healthy controls (CN), and to explore the association between network metrics and patients’ clinical symptoms. Twenty-six patients with MDD and 25 CN were included. A baseline 24-item Hamilton rating scale for depression (HAMD-24) score ≥ 21 and seven factors (anxiety/somatization, weight loss, cognitive disturbance, diurnal variation, retardation, sleep disturbance, hopelessness) scores were assessed. When compared with healthy subjects, significantly higher characteristic path length and clustering coefficient as well as significantly lower network efficiencies were observed in patients with MDD. Furthermore, MDD patients demonstrated significantly lower nodal degree and nodal efficiency in multiple brain regions including superior frontal gyrus (SFG), supplementary motor area (SMA), calcarine fissure, middle temporal gyrus (MTG), and inferior temporal gyrus (ITG). We also found that the characteristic path length of MDD patients was associated with weight loss. Moreover, significantly lower global efficiency of MDD patients was correlated with higher total HAMD score, anxiety somatization, and cognitive disturbance. The nodal degree in SFG was also found to be negatively associated with disease duration. In conclusion, our results demonstrated that MDD patients had impaired structural network features compared to CN, and disruption of optimal network architecture might be the mechanism behind the depressive symptoms and emotion disturbance in MDD patients.

Quality of Life Impacts of Bright Light Treatment, Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome. This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression. Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores. The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.

The concurrent disturbance of dynamic functional and structural brain connectome in major depressive disorder: the prefronto-insular pathway

BackgroundRobust evidence has shown that abnormal function networks, particularly the salience network (SN), are observed in depressed patients. Although white matter structural connectivity may predict time-varying functional connectivity, including symptom phenotype, in psychiatric disorders, there is still a gap in elucidating the concurrent dynamic functional and structural connectivity profiles of the SN in depressed patients. MethodsWe measured static and dynamic functional connectivity (FC) of the SN using resting-state fMRI BOLD time series in 76 subjects (21 with major depressive disorder (MDD), 27 with bipolar depression (BD), and 28 healthy controls (HC)). Hamilton Depression Scale total score was used to measure depression severity. Furthermore, we investigated the concurrent structural connectivity using diffusion kurtosis imaging (DKI)-based tractography. ResultsOur findings suggested that in the presence of MDD, both structural and dynamic (but not static) FC were reduced in the SN, particularly affecting the left prefronto-insular pathways (L.aPFC-L.insula). MDD patients showed decreased connectivity variability within the SN compared with HC. The aberrant dynamic FC in the prefronto-insular pathways of the SN related to severity of depressive symptoms in MDD. Furthermore, compared with BD patients, those with MDD showed significantly decreased dynamic FC in the left prefronto-parietal system (L.aPFC-lateral parietal cortex). LimitationsThe generalizability of our findings is, to some extent, constrained by the small sample size. ConclusionsThe integrity of SN connectivity, particularly the prefronto-insular pathway, appears to be a crucial signature of MDD. The perturbed dynamic interaction of SN with prefrontal regions may underlie the clinical severity in depressed patients.

The problematic use of social networking sites associates with elevated symptoms in patients with major depressive disorder.

Although excessive use of social networking site (SNS) is related to undesired effects on healthy individual's psychological well-being, there is a huge gap in studies performed with individuals who suffer from various mental disorders. The main goal of this study is to examine the association between problematic utilization of SNSs and depressive symptoms across patients diagnosed with major depressive disorder (MDD). 111 patients diagnosed with MDD (diagnoses confirmed via the Structured Clinical Interview for DSM-5-Clinician Version (SCID-5/CV)) and 108 healthy controls (HCs) were recruited for the study. Montgomery-Asberg Depression Rating Scale (MADRS) and Bergen Social Media Addiction Scale (BSMAS) were administered by both MDD and HC groups. Group comparisons were estimated with multivariate analysis of covariance (MANCOVA) analyses. To identify the relationship between SNS addiction and depressive symptoms, the Pearson correlations were performed, and finally, we computed the multiple linear regression analyses to determine whether SNS addiction predicts depressive symptoms. The results revealed that MDD group is more addicted to SNS relative to HC. In addition, depressive symptoms were significantly predicted by 'relapse' subdimension and the overall score of SNS addiction in the MDD group. Our study illustrated the detrimental effects of excessive SNSs usage on depressive symptoms in MDD particularly for the individuals in 'relapse' state of SNS addiction. The mental health workers should consider the usage patterns of SNSs in patients diagnosed with MDD during their clinical observation and management.

Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L'humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse.

Objective:Addiction comorbidity is an important clinical challenge in mood disorders, but the best way of pharmacologically treating people with mood disorders and addictions remains unclear. The aim of this study was to assess the efficacy of pharmacological treatments for mood and addiction symptoms in people with mood disorders and addiction comorbidity.Methods:A systematic search of placebo-controlled randomized controlled trials investigating the effects of pharmacological treatments in people with bipolar disorder (BD) or major depressive disorder (MDD), and comorbid addictions was performed. Treatment-related effects on mood and addiction measures were assessed in a meta-analysis, which also estimated risks of participant dropout and adverse effects.Results:A total of 32 studies met systematic review inclusion criteria. Pharmacological therapy was more effective than placebo for improving manic symptoms (standardized mean difference [SMD] = −0.15; 95% confidence interval [95% CI], −0.29 to −0.02; P = 0.03) but not BD depressive symptoms (SMD = −0.09; 95% CI, −0.22 to 0.03; P = 0.15). Quetiapine significantly improved manic symptoms (SMD = −0.23; 95% CI, −0.39 to −0.06; P = 0.008) but not BD depressive symptoms (SMD = −0.07; 95% CI, −0.23 to 0.10; P = 0.42). Pharmacological therapy was more effective than placebo for improving depressive symptoms in MDD (SMD = −0.16; 95% CI, −0.30 to −0.03; P = 0.02). Imipramine improved MDD depressive symptoms (SMD = −0.58; 95% CI, −1.03 to −0.13; P = 0.01) but Selective serotonin reuptake Inhibitors (SSRI)-based treatments had no effect (SMD = −0.06; 95% CI, −0.30 to 0.17; P = 0.60). Pharmacological treatment improved the odds of alcohol abstinence in MDD but had no effects on opiate abstinence.Conclusions:Pharmacological treatments were significantly better than placebo in improving manic symptoms, MDD depressive symptoms, and alcohol abstinence but were not better for bipolar depression symptoms. Importantly, quetiapine was not more effective than placebo in improving bipolar depression symptoms nor were SSRI’s for the treatment of MDD depression. Our findings highlight the need for further high-quality clinical trials of treatments for mood disorders and comorbid addictions.

Impact of Atypical Antipsychotics as Adjunctive Therapy on Psychiatric Cost and Utilization in Patients with Major Depressive Disorder.

IntroductionPatients with major depressive disorder (MDD) incur high costs, despite established treatment options. Adding an atypical antipsychotic (AAP) to antidepressant therapy has shown to reduce depressive symptoms in MDD, but it remains unclear with which adjunctive AAP to initiate. As economic burden is one factor that can influence treatment selection, this study’s objective was to evaluate the impact of adjunctive AAP choice on psychiatric costs and healthcare utilization in MDD.Materials and MethodsThis retrospective cohort study analyzed de-identified data from: (1) IBM® MarketScan® Commercial (C), Medicare Supplemental (MS), and MarketScan Multi-State Medicaid (M) Databases, and (2) Optum® Clinformatics® Datamart. Adult MDD patients were included if they had: initiated adjunctive AAPs during study identification period (7/1/15-9/30/16 MarketScan C/MS, and Optum; 7/1/15-6/30/16 MarketScan M), and ≥12 months of continuous enrollment before (baseline) and after (follow-up) first treatment date. Models included generalized linear models (GLMs) for psychiatric costs (total inpatient and outpatient services, excluding outpatient pharmacy costs), and a two-part model (logistic regression for psychiatric hospitalizations, GLM for psychiatric hospitalization costs among hospitalized patients); models were adjusted for baseline characteristics.ResultsThe final study sample consisted of 10,325 patients (7657 aripiprazole, 1219 brexpiprazole, 827 lurasidone, 622 quetiapine). Using brexpiprazole as reference, lurasidone and quetiapine users had $1662 and $3894 higher psychiatric costs, respectively. Psychiatric costs were not statistically significantly different between aripiprazole and brexpiprazole (p>0.05). Quetiapine users had $15,159 (p<0.001) higher psychiatric hospitalization costs among those hospitalized, and higher odds of psychiatric hospitalization [2.11 (1.46–3.04); p<0.001] compared to brexpiprazole users. No statistically significant differences observed in psychiatric hospitalization risk comparing aripiprazole and lurasidone with brexpiprazole (p>0.05).ConclusionIn MDD, brexpiprazole users had significantly lower psychiatric costs than lurasidone and quetiapine users, and significantly lower psychiatric hospitalization risk than quetiapine users. Adjunctive AAP choice may impact subsequent healthcare costs and utilization in MDD.

Regional cerebral metabolism alterations affect resting-state functional connectivity in major depressive disorder.

18F-FDG positron emission tomography (PET) is a reliable technique to quantify regional neural glucose metabolism even with major depressive disorder (MDD) heterogeneous features. Previous study proposed that in the resting-state (RS), pairs of brain regions whose regional glucose metabolic rates were significantly correlated were functionally associated. This synchronicity indicates a neuronal metabolic and functional interaction in high energy efficient brain regions. In this study, a multimode method was used to identify the RS-FC patterns based on regional metabolism changes, and to observe its relationship with the severity of depressive symptoms in MDD patients. The study enrolled 11 medication-naive MDD patients and 14 healthy subjects. All participants received a static 18F-FDG PET brain scan and a resting-state functional magnetic resonance imaging (RS-fMRI) scan. SPM5 software was used to compare brain metabolism in MDD patients with that in healthy controls, and designated regions with a change in metabolism as regions of interest (ROIs). The glucose metabolism-based regional RS-FC Z values were compared between groups. Then group independent component analysis (ICA) was used to identify the abnormal connectivity nodes in the intrinsic function networks. Finally, the correlation between abnormal RS-FC Z values and the severity of depressive symptoms was evaluated. Patients with MDD had reduced glucose metabolism in the putamen, claustrum, insular, inferior frontal gyrus, and supramarginal gyrus. The metabolic reduction regions impaired functional connectivity (FC) to key hubs, such as the Inferior frontal gyrus (pars triangular), angular gyrus, calcarine sulcus, middle frontal gyrus (MFG), located in dorsolateral prefrontal cortex (DLPFC)/parietal lobe, salience network (SN), primary visual cortex (V1), and language network respectively. There was no correlation between aberrant connectivity and the severity of clinical symptoms. This research puts forward a possibility that focal neural activity alteration may share RS-FC dysfunction and be susceptible to hubs in the functional network in MDD. In particular, the metabolism and function profiles of the Inferior frontal gyrus (pars triangularis) should be emphasized in future MDD studies.

A Meta-Analysis of Memantine forDepression.

We conducted a systematic review and meta-analysis on whether memantine was beneficial for the treatment of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). The analysis included double-blind, randomized, placebo-controlled trials of memantine in MDD and BD. The primary outcome measures for efficacy and safety were response rate and all-cause discontinuation, respectively. Risk ratio (RR) and standardized mean difference with 95% confidence intervals (95% CI) were calculated. We identified six trials including 451 patients: MDD, four trials (n = 189), three of which studied memantine augmentation for antidepressants; BD, two trials (n = 262), both on memantine augmentation for mood stabilizers. The mean study duration was 8.33 weeks, and the mean age of patients was 39.9 years. Memantine was not superior to placebo with regard to response rate (RR = 0.92, 95% CI = 0.70-1.20, I2 = 72%), remission rate, improvement of depressive symptoms scale score, all-cause discontinuation (RR = 0.84, 95% CI = 0.60-1.18, I2 = 0%), discontinuation due to inefficacy and adverse events, or incidence of individual adverse events including decreased appetite, dizziness, nausea, and sedation. Although we conducted sensitivity analyses of the response rate to determine the reasons for the heterogeneity (diagnosis, age of patients, memantine dose, memantine augmentation, geographical region, and statistical population), we did not seek confounding factors. Memantine did not improve the treatment efficacy for depressive symptoms in MDD and BD patients. Long-term study of memantine for depression is required.

Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.

Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114–0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I2=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009–0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017–0.01144), P=0.044) and earlier publication year (β=−0.0735 (−0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.

Affective temperaments play an important role in the relationship between childhood abuse and depressive symptoms in major depressive disorder

Previous studies have shown that various factors, such as genetic and environmental factors, contribute to the development of major depressive disorder (MDD). The aim of this study is to clarify how multiple factors, including affective temperaments, childhood abuse and adult life events, are involved in the severity of depressive symptoms in MDD. A total of 98 participants with MDD were studied using the following self-administered questionnaire surveys: Patient Health Questionnaire-9 measuring the severity of depressive symptoms; Life Experiences Survey (LES) measuring negative and positive adult life events; Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A) measuring affective temperaments; and the Child Abuse and Trauma Scale (CATS) measuring childhood abuse. The data were analyzed using single and multiple regression analyses and structural equation modeling (SEM). The neglect score reported by CATS indirectly predicted the severity of depressive symptoms through affective temperaments measured by TEMPS-A in SEM. Four temperaments (depressive, cyclothymic, irritable, and anxious) directly predicted the severity of depressive symptoms. The negative change in the LES score also directly predicted severity. This study suggests that childhood abuse, especially neglect, indirectly increases the severity of depressive symptoms through increased scores of affective temperaments in MDD.