Abnormalities in the fatty acid composition of the postmortem entorhinal cortex of patients with schizophrenia,bipolar disorder,and major depressive disorder

Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n−3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n−6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n−3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n−6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions.     

Fatty acid composition in the postmortem amygdala of patients with schizophrenia, bipolar disorder, and major depressive disorder

Previous studies with postmortem brain tissues showed abnormalities in n-3 polyunsaturated fatty acids (PUFAs) in the orbitofrontal cortex of individuals with schizophrenia and mood disorders. However, in the hippocampus, we were not able to find any significant differences in PUFAs except for small differences in n-6 PUFAs. In the present study we investigated levels of PUFAs in the amygdala of postmortem brains from patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD) compared with those of unaffected controls. Amygdala samples from patients with schizophrenia (n = 15), bipolar disorder (n = 15), or MDD (n = 15), and controls matched for age, sex, and five other confounding factors (n = 15) were analyzed for fatty acid composition by gas chromatography. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we were unable to find any significant differences in major PUFAs. The relative compositions of docosahexaenoic acid (DHA), the major n-3 PUFA, were 10.0 ± 1.1%, 10.0 ± 1.3%, 9.3 ± 1.3%, and 9.7 ± 1.1%, respectively, in patients with schizophrenia, bipolar disorder, and MDD and unaffected controls (not significantly different). The corresponding relative compositions of arachidonic acid (AA), the major n-6 PUFA, were 9.0 ± 0.8%, 9.2 ± 0.5%, 9.4 ± 0.7%, and 9.4 ± 0.7%, respectively (not significantly different). Significant differences were found in some of the other fatty acids. In particular, we found a 6.5% increase in palmitic acid and 6.2% decrease in oleic acid in patients with MDD compared to controls. With regard to schizophrenia, there was an 8.0% decrease in docosatetraenoic acid compared to controls. In conclusion, the changes in DHA and/or AA seen in orbitofrontal cortex and hippocampus were not observed in amygdala. These changes may be specific to particular brain regions.     

Alterations in white matter network dynamics in patients with schizophrenia and bipolar disorder

Emerging evidence suggests white matter network abnormalities in patients with schizophrenia (SZ) and bipolar disorder (BD), but the alterations in dynamics of the white matter network in patients with SZ and BD are largely unknown. The white matter network of patients with SZ (n = 45) and BD (n = 47) and that of healthy controls (HC, n = 105) were constructed. We used dynamics network control theory to quantify the dynamics metrics of the network, including controllability and synchronizability, to measure the ability to transfer between different states. Experiments show that the patients with SZ and BD showed decreasing modal controllability and synchronizability and increasing average controllability. The correlations between the average controllability and synchronizability of patients were broken, especially for those with SZ. The patients also showed alterations in brain regions with supercontroller roles and their distribution in the cognitive system. Finally, we were able to accurately discriminate and predict patients with SZ and BD. Our findings provide novel dynamic metrics evidence that patients with SZ and BD are characterized by a selective disruption of brain network controllability, potentially leading to reduced brain state transfer capacity, and offer new guidance for the clinical diagnosis of mental illness.     

Shared and Specific Patterns of Structural Brain Connectivity Across Affective and Psychotic Disorders

BackgroundAltered brain structural connectivity has been implicated in the pathophysiology of psychiatric disorders including schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). However, it is unknown which part of these connectivity abnormalities are disorder specific and which are shared across the spectrum of psychotic and affective disorders. We investigated common and distinct brain connectivity alterations in a large sample (N = 1743) of patients with SZ, BD, or MDD and healthy control (HC) subjects.MethodsThis study examined diffusion-weighted imaging-based structural connectome topology in 720 patients with MDD, 112 patients with BD, 69 patients with SZ, and 842 HC subjects (mean age of all subjects: 35.7 years). Graph theory–based network analysis was used to investigate connectome organization. Machine learning algorithms were trained to classify groups based on their structural connectivity matrices.ResultsGroups differed significantly in the network metrics global efficiency, clustering, present edges, and global connectivity strength with a converging pattern of alterations between diagnoses (e.g., efficiency: HC > MDD > BD > SZ, false discovery rate–corrected p = .028). Subnetwork analysis revealed a common core of edges that were affected across all 3 disorders, but also revealed differences between disorders. Machine learning algorithms could not discriminate between disorders but could discriminate each diagnosis from HC. Furthermore, dysconnectivity patterns were found most pronounced in patients with an early disease onset irrespective of diagnosis.ConclusionsWe found shared and specific signatures of structural white matter dysconnectivity in SZ, BD, and MDD, leading to commonly reduced network efficiency. These results showed a compromised brain communication across a spectrum of major psychiatric disorders.     

Transdiagnostic time‐varying dysconnectivity across major psychiatric disorders

Dynamic functional connectivity (DFC) analysis can capture time‐varying properties of connectivity. However, studies on large samples using DFC to investigate transdiagnostic dysconnectivity across schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are rare. In this study, we used resting‐state functional magnetic resonance imaging and a sliding‐window method to study DFC in a total of 610 individuals (150 with SZ, 100 with BD, 150 with MDD, and 210 healthy controls [HC]) at a single site. Using k‐means clustering, DFCs were clustered into three functional connectivity states: one was a more frequent state with moderate positive and negative connectivity (State 1), and the other two were less frequent states with stronger positive and negative connectivity (State 2 and State 3). Significant 4‐group differences (SZ, BD, MDD, and HC groups; q < .05, false‐discovery rate [FDR]‐corrected) in DFC were nearly only in State 1. Post hoc analyses (q < .05, FDR‐corrected) in State 1 showed that transdiagnostic dysconnectivity patterns among SZ, BD and MDD featured consistently decreased connectivity within most networks (the visual, somatomotor, salience and frontoparietal networks), which was most obvious in both range and extent for SZ. Our findings suggest that there is more common dysconnectivity across SZ, BD and MDD than we previously expected and that such dysconnectivity is state‐dependent, which provides new insights into the pathophysiological mechanism of major psychiatric disorders.     

Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression

White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = −1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.     

HTR2A−1438A/G polymorphism influences the risk of schizophrenia but not bipolar disorder or major depressive disorder: A meta‐analysis

The incidence of psychiatric disorders has been shown to have a strong genetic component, and we conducted this study to investigate whether the ?1438A/G polymorphism of the HTR2A gene was associated with susceptibility to schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using data obtained from a total 27 studies that investigated an association between the HTR2A ?1438A/G polymorphism and SZ (15), BD (7), and MDD (4). We failed to observe an association between the HTR2A ?1438A/G polymorphism and BD and MDD, and we found contrary results with regard to SZ. Our results showed that the ?1438A/G polymorphism was a risk factor for SZ, especially in Caucasians (allele model: OR, 1.12; 95% CI, 1.05–1.20; I² = 17.3%; dominant model: OR, 1.14; 95% CI, 1.03–1.27; I² = 15.3%; recessive model: OR, 1.20; 95% CI, 1.06–1.37; I² = 0.0%; codominant model 1: OR, 1.16; 95% CI, 1.01–1.32; I² = 0.0%). We found that the association of the HTR2A ?1438A/G polymorphism with SZ depends on the ethnic origin of the study population, and this genetic variant does not modify the susceptibility to BD or MDD. © 2013 Wiley Periodicals, Inc.     

A comparative diffusion tensor imaging study of corpus callosum subregion integrity in bipolar disorder and schizophrenia

Structural magnetic resonance imaging (MRI) studies have provided evidence for corpus callosum (CC) white matter abnormalities in bipolar disorder (BD) and schizophrenia (SZ). These findings include alterations in shape, volume, white matter intensity and structural integrity compared to healthy control populations. Although CC alterations are implicated in both SZ and BD, no study of which we are aware has investigated callosal subregion differences between these two patient populations. We used diffusion tensor imaging (DTI) to assess CC integrity in patients with BD (n=16), SZ (n=19) and healthy controls (HC) (n=24). Fractional anisotropy (FA) of CC subregions was measured using region of interest (ROI) analysis and compared in the three groups. Significant group differences of FA values were revealed in five CC subregions, including the anterior genu, middle genu, posterior genu, posterior body and anterior splenium. FA values of the same subregions were significantly reduced in patients with SZ compared with HC. FA values were also significantly reduced in patients with BD compared to the HC group in the same subregions, excepting the middle genu. No significant difference was found between patient groups in any region. Most of the alterations in CC subregions were present in both the BD and SZ groups. These results imply an overlap in potential pathology, possibly relating to risk factors common to both disorders. The one region that differed between patient groups, the middle genu area, may serve as an illness marker and is perhaps involved in the different cognitive impairments observed in BD and SZ.     

Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder,schizophrenia, and healthy subjects

Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression.     

Associations between major psychiatric disorder polygenic risk scores and blood-based markers in UK biobank

Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors, and are associated with peripheral abnormalities. The relationships between such genetic architectures and blood-based markers are, however, unclear.We investigated relationships between polygenic risk scores (PRS) for these disorders and peripheral markers in the UK Biobank cohort. We calculated polygenic risk scores for n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) UK Biobank cohort subjects. We then examined associations between disorder PRS and 58 inflammatory/immune, hematological, bone, cardiovascular, hormone, liver, renal and diabetes-associated blood markers using two generalized linear regression models: ‘minimally adjusted’ controlling for variables such as age and sex, and ‘fully adjusted’ including additional lifestyle covariates: BMI, alcohol and smoking status, and medication intake.There were 38/58 MDD PRS, 32/58 SCZ PRS, and 20/58 BD PRS-blood marker associations detected for our minimally adjusted model. Of these, 13/38 (MDD PRS), 14/32 (SCZ PRS), and 10/20 (BD PRS) associations remained significant after controlling for lifestyle factors. Many were disorder-specific, with 8/13 unique MDD PRS associations identified. Several disorder-specific associations for MDD and SCZ were immune-related, with mostly positive and negative associations identified for MDD and SCZ PRS respectively.This study suggests that MDD, SCZ and BD have both shared and distinct peripheral markers associated with disorder-specific genetic risk. The results also implicate inflammatory dysfunction in MDD and SCZ, albeit with differences in patterns between the two conditions, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.     

Effect of preexisting borderline personality disorder on clinical and EEG sleep correlates of depression

Two groups of depressed patients were studied: (1) The first group comprised 15 inpatients who were diagnosed as predominantly “borderline personality disorders” based on DSM-III and psychometric test criteria; these patients were also clinically depressed. (2) The second group consisted of 18 inpatients who met Research Diagnostic Criteria (RDC) for major depressive disorder (MDD) but who failed to meet the above criteria for borderline personality disorder. Subsequent to the selection of patients for study, an independent diagnostic evaluation revealed that MDD patients with borderline personality disorder had higher ratings than nonborderline MDD patients on items from the Schedule for Affective Disorders and Schizophrenia such as total anxiety, anger, schizotypal features, miscellaneous psychopathology, and alcohol and drug abuse. A further breakdown of miscellaneous psychopathology items revealed greater subjective anger, self-pity, and demandingness in borderline patients. A comparison of RDC subtypes in the two groups revealed a significant increase in bipolar II diagnoses in the borderline MDD group. Electroencephalographic (EEG) sleep studies carried out in a subsample of MDD borderline (n=8) and primary MDD nonborderline (n=11) patients revealed no significant differences between the two groups. Thus, in contrast to the EEG sleep findings reported for secondary depression with other antecedent psychiatric disorders, the present study indicated that a preexisting diagnosis of borderline personality disorder in MDD patients did not alter the characteristics short latency of rapid eye movement (REM) sleep and the sleep continuity disturbances reported in primary MDD. These data confirm earlier reports by Akiskal (1981), Carroll et al. (1981), and McNamara et al. (1982) concerning the phenomenological and EEG sleep profiles of borderline patients.     

Functional outcome in major psychiatric disorders and associated clinical and psychosocial variables: A potential cross-diagnostic phenotype for further genetic investigations?

Objectives. Functional outcome has recently become of interest for cross-diagnostic subphenotype approaches in psychiatric genetics. Therefore, it is crucial to know about clinical, demographic and psychosocial variables that correlate with long-term functioning. Unfortunately, there is a lack of studies that directly compare the importance of correlates for functional outcome between different disorders. Methods. Applying regression models to samples of patients with schizophrenia (SZ, n = 238), bipolar disorder (BD, n = 533) and major depressive disorder (MDD, n = 398), we compared the magnitude of association of potential correlates with functional outcome, measured by the Global Assessment of Functioning (GAF) score. Results. Shared correlates for worse functional outcome were poor premorbid functioning, insidious illness onset and poor premorbid work or social adjustment in all three disorders, and negative symptomatology in SZ and BD. Disorder-specific correlates for SZ were longer duration of illness, lower functioning during episodes and being life-time single, for BD substance abuse and suicidality, and for MDD premorbid unemployment and having a premorbid personality disorder. Conclusions. We found different patterns of correlates for long-term functioning in SZ, BD and MDD. Knowledge of these patterns may improve the quality of genetic investigations focussing on functional outcome.     

Brief report: Overgeneral autobiographical memory in adolescent major depressive disorder

The current study examined whether overgeneral autobiographical memory (OGM) bias serves as a state-like marker of major depressive disorder (MDD) in adolescence or whether it would also be observed in currently nondepressed adolescents with a history of MDD. We examined differences in OGM to positive and negative cue words between adolescents (aged 11–18 years) with current MDD (n = 15), remitted MDD (n = 25), and no history of any depressive disorder (n = 25). Youth and their parents were administered a structured diagnostic interview and adolescents completed the autobiographical memory test. Compared to never depressed adolescents, adolescents with current or remitted MDD recalled less specific memories in response to positive and negative cue words. The difference between the two MDD groups was small and nonsignificant. These findings suggest that OGM is not simply a state-like marker in currently depressed adolescents, but is also evident in adolescents with remitted MDD, indicating that it may represent a trait-like vulnerability that increases risk for relapse.     

A Comparative Multimodal Meta-analysis of Anisotropy and Volume Abnormalities in White Matter in People Suffering From Bipolar Disorder or Schizophrenia

Schizophrenia (SZ) and bipolar disorder (BD) share some similarities in terms of genetic-risk genes and abnormalities of gray-matter structure in the brain, but white matter (WM) abnormalities have not been studied in depth. We undertook a comparative multimodal meta-analysis to identify common and disorder-specific abnormalities in WM structure between SZ and BD. Anisotropic effect size-signed differential mapping software was used to conduct a comparative meta-analysis of 68 diffusion tensor imaging (DTI) and 34 voxel-based morphometry (VBM) studies comparing fractional anisotropy (FA) and white matter volume (WMV), respectively, between patients with SZ (DTI: N = 1543; VBM: N = 1068) and BD (DTI: N = 983; VBM: N = 518) and healthy controls (HCs). The bilateral corpus callosum (extending to the anterior and superior corona radiata) showed shared decreased WMV and FA in SZ and BD. Compared with BD patients, SZ patients showed remarkable disorder-specific WM abnormalities: decreased FA and increased WMV in the left cingulum, and increased FA plus decreased WMV in the right anterior limb of the internal capsule. SZ patients showed more extensive alterations in WM than BD cases, which may be the pathophysiological basis for the clinical continuity of both disorders. The disorder-specific regions in the left cingulum and right anterior limb of the internal capsule provided novel insights into both disorders. Our study adds value to further understanding of the pathophysiology, classification, and differential diagnosis of SZ and BD.     

An fMRI study of cognitive reappraisal in major depressive disorder and borderline personality disorder

BackgroundOne common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations.MethodsWe contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity.ResultsWhen compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal.ConclusionsThis study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders.     

Serum testosterone levels in bipolar and unipolar depressed female patients and the role of medication status

Abstract

Objective: to compare testosterone levels between female depressed patients and female bipolar patients.

Methods: Sixty-one female patients with major depressive disorder (MDD) (n?=?23) or bipolar disorder (BD) (n?=?38) between 18 and 45?years old were included in the study. Participants were evaluated during a depressive or manic episode with the Hamilton depression rating scale (HDRS) or Young mania rating scale (YMRS), respectively. No patients in the MDD group were taken valproate while in the BD group 14 (36.84%) were taken valproate. Total testosterone (TT) and free testosterone (FT) levels were quantified during the early follicular phase of the cycle, with radioimmunoassay or solid phase enzyme-linked immunoassay. Data were collected from May 2016 to February 2017.

Results: Mean TT serum levels were significantly higher in BD patients in comparison to MDD patients. Although age and diagnosis were related to TT levels, however when we added valproate use in the analysis, only the relation between TT and valproate use remained significant.

Conclusions: In this sample, TT levels were related to valproate use in patients with BD. More studies regarding the role of testosterone in affective symptoms should be conducted to clarify the relation between testosterone, affective disorders, and medication.

• Keypoints

• We observed that testosterone levels were significant higher in bipolar women compared to women with MDD.

• The use of valproate could be associated with the testosterone levels in female patients with BD.

• Evaluation of women suffering BD should include a testosterone levels determination, particularly when they are taking valproate.

     

Thalamo-cortical functional connectivity in schizophrenia and bipolar disorder

The thalamus is a highly connected subcortical structure that relays and integrates sensory and cortical information, which is critical for coherent and accurate perceptual awareness and cognition. Thalamic dysfunction is a classical finding in schizophrenia (SZ), and resting-state functional MRI has implicated somatomotor and frontal lobe thalamic dysconnectivity. However, it remains unclear whether these findings generalize to different psychotic disorders, are confined to specific thalamic sub-regions, and how they relate to structural thalamic alterations. Within-thalamic and thalamo-cortical functional connectivity was assessed using resting-state functional MRI data obtained from patients with SZ (n = 96), bipolar disorder (BD, n = 57), and healthy controls (HC, n = 280). Further, we used thalamic sub-regions as seeds to investigate specific cortical connectivity patterns, and performed structural analyses of thalamic volume and shape. Results showed reduced within-thalamic connectivity and thalamo-frontoparietal coupling in SZ and increased thalamo-somatomotor connectivity in BD. One thalamic sub-region showed increased sensory connectivity in SZ and eight sub-regions showed reductions with frontal and posterior areas. Reduced gray matter and shape abnormalities were found in frontal-projecting regions in both SZ and BD, but did not seem to explain reduced functional connectivity. Aberrant thalamo-cortical connectivity patterns in SZ and BD supports the notion of the thalamus as a key structure in the functional connectome across the psychosis spectrum, and the frontal and somatomotor anatomical distribution is in line with the characteristic cognitive and perceptual symptoms in psychotic disorders.     

Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder

Background

Major depressive disorder (MDD) is a debilitating mental illness and a major cause of lost productivity worldwide. MDD patients often suffer from lifelong recurring episodes of increasing severity, reduced therapeutic response, and shorter remission periods, suggesting the presence of a persistent and potentially progressive pathology.