Comorbid Major Depressive Disorder Research Articles

Brain single-cell transcriptomics highlights comorbidity-related cell type-specific changes of Parkinson’s disease with major depressive disorder after paraquat exposure

Paraquat (PQ), a commonly used herbicide, is a potent environmental neurotoxin associated with Parkinson’s disease (PD) and major depressive disorder (MDD). While the involvement of various brain cell types in the etiology of each disorder is well recognized, the specific cell subtypes implicated in the comorbidity of PD and MDD, especially under PQ neurotoxicity, remain poorly understood. In this study, we used single-cell RNA sequencing (scRNA-seq) to analyze brain tissues from mice with PQ-induced PD with MDD. By integrating genomic data with scRNA-seq profiles, we identified differences in cellular heterogeneity related to the pathogenesis of PD and MDD under PQ exposure. Our analysis of risk enrichment in genes with cell type-specific expression patterns revealed that astrocytes are predominantly linked to the comorbidity of PQ-induced PD and MDD. Furthermore, we identified a specific astrocyte subtype that plays a major role in the comorbidity-related changes observed in PQ-induced PD and MDD. This subtype appears to interact with and potentially transform into MDD-specific and PD-specific subtypes. Additionally, pathways related to chemical synaptic function and neuro-projection development were involved in all key stages of PD and MDD co-occurrence. We also identified RNF7 and MTCH2 as shared diagnostic hub genes for PD and MDD, which changed significantly in astrocytes following PQ exposure. These genes may serve as potential markers for astrocyte-specific prognostic diagnosis of PQ-induced PD with MDD. In summary, this study provides the first scRNA-seq profile of comorbidity in a PQ-exposed model. It highlights the heterogeneity of astrocytes in comorbidity and elucidates potential mechanisms underlying the co-occurrence of PD and MDD. These findings emphasize the need for further research into the pathogenesis of PD comorbid with MDD and offer novel insights into PQ neurotoxicity.

A comparative study of comorbidities, symptom profiles, and childhood trauma in PTSD and non-PTSD trauma patients at Oslo University Hospital

Purpose To explore the differences in mental health symptom profiles, trauma profiles, childhood trauma and comorbidities in patients with PTSD and those without PTSD. Materials and methods A cross-sectional study was carried out on 110 adult patients with trauma backgrounds attending a mental health outpatient clinic in Southern Oslo, Norway. In addition to self- report questionnaires, several standardized validated diagnostic tools were used to assess mental disorders. Multiple linear regression models were used to assess the association between trauma history, the mental health symptom profile of the patients, and PTSD diagnosis. Bivariate logistic regression was used to examine if childhood trauma/adversities were associated with PTSD. Results Patients diagnosed with PTSD had significantly higher rates of comorbid major depressive disorder, panic disorder, agoraphobia disorder, and social phobia compared to those without PTSD. We also found a positive association between PTSD diagnosis and all the different mental health symptoms domains of the Symptom Checklist-90-Revised instrument. When adjusted for age, gender, education, smoking habits, immigration, relationship, and employment status, these associations persisted with varying effects. We did not find any association between PTSD and childhood trauma/adversities, however, sexual abuse trended towards an association. Conclusion Adult trauma patients with PTSD may have more comorbid disorders and mental health symptoms. Childhood trauma may be less critical for the PTSD diagnosis in this group. In clinical practice, personalized treatment plans addressing both the symptom burden and its comorbidities may be beneficial.

Standardized weighted low-resolution electromagnetic tomography study of the amygdala activity in patients with comorbid major depressive disorder and anxiety symptoms

Major depressive disorder (MDD) often coexists with anxiety disorders or symptoms, as identified by previous functional magnetic resonance imaging (fMRI) studies. These studies have found abnormal amplitudes of low-frequency fluctuations (ALFF) in the amygdala, which serve as traits and state markers of MDD. This study used standardized weighted low-resolution electromagnetic tomography (swLORETA) technology to explore amygdala markers in patients with comorbid MDD and anxiety. Participants included patients with MDD comorbid with anxiety symptoms (MDD group) and healthy controls (HC group) who completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). EEG data collected under resting state, happiness recall, and depressive recall tasks were converted into current-source density (CSD) values using swLORETA to assess amygdala activation. The results indicated higher beta2, beta3, and high beta levels in both the left and right amygdalae during the resting state in the MDD group than in the HC group. Similarly, elevated levels of beta2, beta3, and high beta were observed in the left and right amygdalae of the MDD group during happiness and depressive recall tasks. These findings support the presence of hyperactivity in the amygdala under resting state and emotional tasks in patients with comorbid MDD and anxiety symptoms.

Safety and efficacy of targeting the supplementary motor area with double-cone deep transcranial magnetic stimulation vs figure-eight coil in treatment of obsessive-compulsive disorder with comorbid major depressive disorder

Background and objectiveThe Supplementary Motor Area (SMA), a relatively large brain structure predominantly located along the interhemispheric fissure, is an established target for repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Obsessive-Compulsive Disorder (OCD). We investigated the feasibility, safety, and efficacy of targeting SMA using a double-cone “deep” TMS coil compared to conventional figure-eight coil for treatment of OCD with comorbid Major Depressive Disorder (MDD). MethodsSixty-two patients with treatment-resistant OCD and comorbid MDD participated in the study. All patients received high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) with a figure-eight coil (MagVenture B70), followed by 1 Hz rTMS over the bilateral SMA using either the B70 (N = 25) or double-cone deep coil (MagVenture DB80) (n = 23) for 36 treatment sessions. Weekly clinical assessments were conducted. ResultsSubjects overall had significant reductions in OCD and depressive symptom severity at the primary endpoint. Subjects stimulated at SMA with the double-cone deep coil had statistically significantly lesser reductions in overall OCD and depression symptom severity compared to the figure-eight group. The intensity of stimulation at SMA was significantly greater with the double-cone deep than figure-eight coil and e-field modeling showed that it affected broader regions beyond SMA (off-target stimulation). There was no significant difference in reported tolerability between groups. ConclusionsSMA stimulation using either a double-cone deep or conventional figure-of-eight coil was safe and was associated with a significant reduction in comorbid OCD and depression symptoms, but the higher intensities of stimulation with the double-cone deep coil used in this study were significantly less clinically beneficial than figure-eight coil stimulation.

Acceptance and Commitment Therapy (ACT) and Self-Compassion for Generalized Anxiety Disorder and Comorbid Major Depressive Disorder: A Case Study

The current case describes the implementation of Acceptance and Commitment Therapy (ACT) and self-compassion interventions with a 37-year-old Queer Hispanic woman “Cynthia” (pseudonym). Cynthia presented to a university training clinic, reporting pervasive difficulties with anxiety, an associated pattern of depressive episodes, and a trauma history. The therapist conceptualized Cynthia’s presenting problems through an ACT-based psychological flexibility framework. Functional analysis indicated intolerance of uncertainty, fusion to self-critical thoughts, and experientially avoidant behaviors (e.g., pervasive worry) contributed to Cynthia’s anxiety. Values clarification, as well as mindfulness- and acceptance-based interventions, were met with gains in quality-of-life scores and decreases in worry scores as treatment progressed. Additionally, self-compassion interventions were implemented to address pervasive self-criticism and feelings of low self-worth. Across 37 sessions, from pre-to-post treatment, Cynthia’s quality of life scores increased by 62.5%, and worry decreased by 52.8%. These results provide support for using ACT and self-compassion interventions for anxiety and co-occurring depression with a Queer, Hispanic woman.

The unique face of comorbid anxiety and depression: Increased frontal, insula and cingulate cortex response during Pavlovian fear-conditioning

BackgroundDysregulation of fear processing through altered sensitivity to threat is thought to contribute to the development of anxiety disorders and major depressive disorder (MDD). However, fewer studies have examined fear processing in MDD than in anxiety disorders. The current study used propensity matching to examine the hypothesis that comorbid MDD and anxiety (AnxMDD) shows greater neural correlates of fear processing than MDD, suggesting that the co-occurrence of AnxMDD is exemplified by exaggerated defense related processes. Methods195 individuals with MDD (N = 65) or AnxMDD (N = 130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. Visual images paired with threat (conditioned stimuli: CS+) were compared to stimuli not paired with threat (CS-). ResultsMDD and AnxMDD showed significantly different patterns of activation for CS+ vs CS- in the dorsal anterior insula/inferior frontal gyrus (partial eta squared; ηp2 = 0.02), dorsolateral prefrontal cortex (ηp2 = 0.01) and dorsal anterior/mid cingulate cortex (ηp2 = 0.01). These differences were driven by greater activation to the CS+ in AnxMDD versus MDD. LimitationsLimitations include the cross-sectional design, a scream US rather than shock and half the number of MDD as AnxMDD participants. ConclusionsAnxMDD showed a pattern of increased activation in regions identified with fear processing. Effects were consistently driven by threat, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, self-relevant processing and executive functioning in comorbid anxiety and depression, thereby highlighting potential treatment targets for this prevalent and treatment resistant group.

Prevalence of autoimmune diseases in functional neurological disorder: influence of psychiatric comorbidities and biological sex

BackgroundFunctional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared with men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging...

Healthcare resource utilisation and suicidal ideation amongst adolescents in the US with posttraumatic stress disorder, major depressive disorder, and substance use disorders using electronic health records

BackgroundWhile PTSD is commonly associated with multiple comorbidities, studies have yet to quantify the impact of these comorbidities on key clinical outcomes and HCRU. This study explored risks of emergency room (ER) visits, inpatient admissions (IA), suicidal ideation (SI), and treatment follow-up duration (FU), amongst PTSD patients with comorbid MDD and/or SUD. MethodsUsing real-world data (RWD) generated by electronic health records accessed from the NeuroBlu database, a cohort of adolescent patients (12-17 yrs) was examined over a one-year study period following PTSD diagnosis. Results5794 patients were included in the cohort. Compared to patients with only PTSD (n = 3061), those with comorbid MDD (n = 1820) had greater odds of ER (4.5 times), IA (1.6 times), and FU (4.3 times). Those with comorbid SUD (n = 653) had greater odds of IA (4.5 times), shorter FU (34 days), and lower odds of ER (0.5 times). Both comorbidities (n = 260) had greater odds of ER (3.8 times), IA (2.6 times), SI (3.6 times), and shorter FU (12 days). LimitationsThese RWD had a high proportion of missingness. Health records of patients who changed service providers could not be accounted for in this study. ConclusionsBoth MDD and SUD substantially elevated the risk of HCRU and suicidal ideation for PTSD patients.

Dihydroergotamine and Bromocriptine: Potential Drugs for the Treatment of Major Depressive Disorder and Alzheimer's Disease Comorbidity.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease that is characterized by memory loss and cognitive impairment. Evidence shows that depression is a common co-occurrence in AD patients, and major depressive disorder (MDD) is considered a risk factor for AD. The crosstalk between the biological procedures related to the two disorders makes it very difficult to treat the comorbid conditions caused by them. Considering the common pathophysiological mechanisms underlying AD and MDD, antidepressant drugs may have beneficial therapeutic effects against their concurrence. In this study, we aimed to explore the potential drug candidates for the prevention and treatment of the comorbidity of AD and MDD. First, we screened the potential drugs for treating MDD by evaluating the distances of drug targets to MDD-related genes on the human protein-protein interaction network (PPIN) via a network-based algorithm. Then, the drugs were further screened to identify those that may be effective for AD treatment by analyzing their affinities with tau protein and Aβ42 peptide via molecular docking. Furthermore, the most stable binding modes were identified via molecular dynamics simulations, and the regulatory effects of drug candidates on genes involved in the pathogenesis of AD and MDD were analyzed. A total of 506 MDD-related genes were retrieved, and 831 drug candidates for MDD treatment were screened via the network-based approach. The results from molecular docking and molecular dynamics simulations indicated dihydroergotamine had the lowest binding affinity with tau protein and bromocriptine could form the most stable binding mode with Aβ42 peptide. Further analyses found that both dihydroergotamine and bromocriptine could regulate the expression of genes involved in the pathogenesis of AD and/or MDD in the brain. The exact mechanisms of the two drugs in treating AD and MDD, as well as their comorbidity, are still unclear, and further exploration is needed to evaluate their roles and mechanisms, both in vitro and in vivo. This study revealed that dihydroergotamine and bromocriptine may be the potential drug candidates for the treatment of the comorbidity of AD and MDD, and the therapeutic effects may be achieved by inhibiting the accumulation and aggregation of Aβ42 and tau protein and regulating the expression of disease-related genes in the brain.

Potential Shared Mitochondrial-Related Gene Signatures and Molecular Mechanisms Between Polycystic Ovary Syndrome (PCOS) and Major Depressive Disorder (MDD): Evidence from Transcriptome Data and Machine Learning.

Polycystic ovary syndrome (PCOS) is strongly associated with major depressive disorder (MDD), but the shared pathophysiological mechanisms between them are ambiguous, and the aim of this study was to explore the shared genetic features and associated pathways between these two disorders. MDD-related genes and mitochondrial function genes were downloaded from the GeneCards database. Weighted gene co-expression network analysis of Merge Cohort (GSE80432 and GSE34526) was performed to identify PCOS-related genes. Overlaps between PCOS-related genes, MDD-related genes, and mitochondrial function genes were defined as mitochondrial function-related shared genes. Functional enrichment analysis and protein-protein interaction (PPI) network analysis were performed on the shared genes. Functional genes were then identified using Last Absolute Shrinkage and Selection Operator Regression (LASSO), and a support vector machine (SVM-RFE) was constructed to measure the accuracy of the calculations. Finally, the results were tested using the whole blood datasets GSE54250 (for PCOS) and GSE98793 (for MDD) as external validation sets. A total of 498 PCOS-related genes, 5909 MDD-related genes, and 7232 mitochondrial function genes were acquired, and totally, 40 shared genes were obtained from the overlap of the above three. The shared mitochondrial function genes were enriched for biological processes mainly involving cholesterol biosynthetic process, lipid metabolic process, triglyceride biosynthetic process, response to drug phosphatidic acid biosynthetic process, and endoplasmic reticulum membrane. Based on LASSO regression and SVM-RFE model, NPAS2 and NTS were identified as characteristic genes shared by two disorders. According to two external validation sets for PCOS and MDD, NPAS2 was finally identified as a key shared gene. Our analysis identified a mitochondrial functional gene-NPAS2-as the most critical candidate for linking PCOS and MDD. The present findings may provide new insights into the diagnosis and treatment of PCOS and MDD comorbidities.

Evaluation of serum zonulin and occludin levels in obsessive-compulsive disorder and the effect of major depressive disorder comorbidity.

The aim of this study is to determine whether the levels of zonulin and occludin, tight junctions (TJ) proteins in the intestinal epithelium, will differ between obsessive compulsive disorder (OCD) patients and healthy controls. We also intended to investigate whether these would vary in OCD patients with and without major depressive disorder (MDD) comorbidity and in comparison with healthy controls. Sixty patients diagnosed with OCD and 30 healthy controls were included in the study. The cases were administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HDRS). The patients were divided into two subgroups based on their HDRS scores and presence of MDD comorbidity. Zonulin and occludin levels were measured using the ELISA method. The research was carried out between April 2021 and October 2021. Zonulin and occludin levels were significantly higher in the OCD patient group than in the control group (p<0.001). The levels of both were also significantly higher in the OCD patients with MDD comorbidity (OCD+MDD) compared to those without MDD (OCD-MDD) (p<0.001). Zonulin and occludin levels also rose significantly as disease severity increased in the OCD patient group (respectively; p<0.001, p=0.001). The levels of both increased in line with the severity of depression based on HDRS scores in the OCD+MDD group (p<0.001). A positive correlation was determined between the duration of OCD and zonulin and occludin levels. Evaluation of the entire OCD group revealed a moderate positive correlation between Y-BOCS and HDRS scores and zonulin and occludin. Zonulin and occludin levels in this research were significantly higher in the patients with OCD than in the healthy controls. That elevation was positively correlated with disease duration and severity, and the increase was significantly more pronounced in OCD with MDD comorbidity. These findings point to a possible disorder in the intestinal barrier and blood-brain barrier in OCD patients.

Social sharing and expressive suppression in major depressive disorder and borderline personality disorder: An experience sampling study

AbstractMajor depressive disorder (MDD) and borderline personality disorder (BPD) are characterized by disturbed patterns of emotional and interpersonal functioning, which might imply altered use of emotion regulation in interpersonal contexts. In the current study, we examined how individuals with MDD and/or BPD differ from healthy controls in (1) their overall daily life use of expressive suppression and social sharing and (2) their tendency to adjust the use of these strategies to the emotional context (i.e., preceding negative and positive affect). Thirty‐four individuals with MDD, 20 individuals with BPD, 19 individuals with comorbid MDD and BPD, and 40 healthy controls participated in a week of experience sampling during which they reported their use of expressive suppression, social sharing, and experienced negative and positive affect. The results indicated that all clinical groups reported more expressive suppression and social sharing in their daily lives than healthy controls. Group differences remained when controlling for differences in mean experienced affect, except for increased suppression for MDD and increased sharing for BPD and comorbid MDD and BPD, which seemed related to these participants' overall higher levels of negative affect. Additionally, associations between within‐person fluctuations in negative or positive affect and subsequent strategy use were equally strong for clinical and control participants, indicating that clinical groups did not differentially adjust the use of suppression and sharing to the emotional context. In conclusion, individuals with MDD and/or BPD showed increased use of suppression and sharing in daily life, which might contribute to, or follow from their emotional and interpersonal difficulties.

Whole-Genome Metagenomic Analysis of the Oral Microbiota in Patients with Obstructive Sleep Apnea Comorbid with Major Depressive Disorder.

Obstructive sleep apnea (OSA) patients commonly experience high rates of depression. This study aims to examine the oral microbiota characteristics of OSA and those with comorbid major depressive disorder (OSA+MDD) patients. Participants were enrolled from Aug 2022 to Apr 2023. Polysomnography, psychiatrist interviews, and scales were used to diagnose OSA and MDD. Oral samples were collected from participants by rubbing swabs on buccal mucosa, palate, and gums. Oral microbiota was analyzed via whole-genome metagenomics and bioinformatic analysis followed sequencing. Venous blood was drawn to detect plasma inflammatory factor levels. The study enrolled 33 OSA patients, 28 OSA+MDD patients, and 28 healthy controls. Significant differences were found in 8 phyla, 229 genera, and 700 species of oral microbiota among the three groups. Prevotellaceae abundance in the OSA and OSA+MDD groups was significantly lower than that in healthy controls. Linear discriminant analysis effect size (LEfSe) analysis showed that Streptococcaceae and Actinobacteria were the characteristic oral microbiota of the OSA and OSA+MDD groups, respectively. KEGG analysis indicates 30 pathways were changed in the OSA and OSA+MDD groups compared with healthy controls, and 23 pathways were changed in the OSA group compared with the OSA+MDD group. Levels of IL-6 in the OSA+MDD group were significantly higher than in the healthy group, correlating positively with the abundance of Schaalia, Campylobacter, Fusobacterium, Alloprevotella, and Candidatus Nanosynbacter in the oral, as well as with Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores. Significant differences in oral microbiota populations and gene function were observed among the three groups. OSA patients were characterized by a decreased abundance of Prevotellaceae and an increased abundance of Streptococcaceae. OSA+MDD patients had an increased abundance of Actinobacteria. IL-6 might regulate the relationship between depression and the oral microbiota in OSA+MDD patients.

Depression in a Case of Mauriac Syndrome

Mauriac syndrome is a rare complication of poorly controlled type 1 diabetes mellitus and is characterized by hepatomegaly with altered liver enzymes, delayed puberty, growth retardation, and cushingoid features, seen in children. Being a chronic condition, warranting frequent hospitalization, and invasive testing and management, one should always look out for the possibility of comorbid depression, enabling timely diagnosis and treatment. Here, we report the case of 14-year-old male with Mauriac Syndrome having comorbid major depressive disorder being well maintained on escitalopram.

Development and validation of a machine learning model for prediction of comorbid major depression disorder among narcolepsy type 1

BackgroundMajor depression disorder (MDD) forms a common psychiatric comorbidity among patients with narcolepsy type 1 (NT1), yet its impact on patients with NT1 is often overlooked by neurologists. Currently, there is a lack of effective methods for accurately predicting MDD in patients with NT1. ObjectiveThis study utilized machine learning (ML) algorithms to identify critical variables and developed the prediction model for predicting MDD in patients with NT1. MethodsThe study included 267 NT1 patients from four sleep centers. The diagnosis of comorbid MDD was based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). ML models, including six full models and six compact models, were developed using a training set. The performance of these models was compared in the testing set, and the optimal model was evaluated in the testing set. Various evaluation metrics, such as Area under the receiver operating curve (AUC), precision-recall (PR) curve and calibration curve were employed to assess and compare the performance of the ML models. Model interpretability was demonstrated using SHAP. ResultIn the testing set, the logistic regression (LG) model demonstrated superior performance compared to other ML models based on evaluation metrics such as AUC, PR curve, and calibration curve. The top eight features used in the LG model, ranked by feature importance, included social impact scale (SIS) score, narcolepsy severity scale (NSS) score, total sleep time, body mass index (BMI), education years, age of onset, sleep efficiency, sleep latency. ConclusionThe study yielded a straightforward and practical ML model for the early identification of MDD in patients with NT1. A web-based tool for clinical applications was developed, which deserves further verification in diverse clinical settings.

Comparative analysis of resting-state EEG functional connectivity in depression and obsessive-compulsive disorder

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) are psychiatric disorders that often co-occur. We aimed to investigate whether their high comorbidity could be traced not only by clinical manifestations, but also at the level of functional brain activity. In this paper, we examined the differences in functional connectivity (FC) at the whole-brain level and within the default mode network (DMN). Resting-state EEG was obtained from 43 controls, 26 OCD patients, and 34 MDD patients. FC was analyzed between 68 cortical sources, and between-group differences in the 4–30 Hz range were assessed via the Network Based Statistic method. The strength of DMN intra-connectivity was compared between groups in the theta, alpha and beta frequency bands. A cluster of 67 connections distinguished the OCD, MDD and control groups. The majority of the connections, 8 of which correlated with depressive symptom severity, were found to be weaker in the clinical groups. Only 3 connections differed between the clinical groups, and one of them correlated with OCD severity. The DMN strength was reduced in the clinical groups in the alpha and beta bands. It can be concluded that the high comorbidity of OCD and MDD can be traced at the level of FC.

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

Borderline personality disorder (BPD) is diagnosed in 10-30% of patients with major depressive disorder (MDD), and the frequency of MDD among individuals with BPD reaches over 80%. The comorbidity of MDD and BPD is associated with more severe depressive symptoms and functional impairment, higher risk of treatment resistance and increased suicidality. The effectiveness of ketamine usage in treatment resistant depression (TRD) has been demonstrated in numerous studies. In most of these studies, individuals with BPD were not excluded, thus given the high co-occurrence of these disorders, it is possible that the beneficial effects of ketamine also extend to the subpopulation with comorbid TRD and BPD. However, no protocols were developed that would account for comorbidity. Moreover, psychotherapeutic interventions, which may be crucial for achieving a lasting therapeutic effect in TRD and BPD comorbidity, were not included. In the article, we discuss the results of a small number of existing studies and case reports on the use of ketamine in depressive disorders with comorbid BPD. We elucidate how, at the molecular and brain network levels, ketamine can impact the neurobiology and symptoms of BPD. Furthermore, we explore whether ketamine-induced neuroplasticity, augmented by psychotherapy, could be of use in alleviating core BPD-related symptoms such as emotional dysregulation, self-identity disturbances and self-harming behaviors. We also discuss the potential of ketamine-assisted psychotherapy (KAP) in BPD treatment. As there is no standard approach to the application of ketamine or KAP in individuals with comorbid TRD and BPD, we consider further research in the field as imperative. The priorities should include development of dedicated protocols, distinguishing subpopulations that may benefit most from such treatment and investigating factors that may influence its effectiveness and safety.

Dropout in a clinical trial for comorbid PTSD and MDD among US service members: Are pretreatment characteristics predictive?

Objective Despite effective treatment options for posttraumatic stress disorder (PTSD), many patients do not complete therapy. This includes U.S. active duty service members, yet factors linked to attendance in this population remain understudied and dropout remains difficult to predict. Additionally, most studies have not examined samples with PTSD and co-occurring major depressive disorder (MDD) despite high rates of comorbidity. Method The current study explored predictors of dropout among service members with comorbid PTSD and MDD (N = 94) randomized to cognitive processing therapy enhanced with behavioral activation (BA + CPT) or CPT as part of a clinical trial. Results Using the Fournier approach, only two predictors were associated with lower dropout risk among over 20 examined: shorter duration between pretreatment assessment and Session 1 (p = .041) and past 3-month PTSD treatment engagement (p = .036). Conclusion Results suggest the possible utility of early momentum in starting therapy and leveraging recent treatment to improve attendance. However, this study also highlights the possible limitations of commonly assessed pretreatment factors in predicting attendance and current challenges in measuring dropout risk. Strategies to improve prediction, such as shifting focus to assess modifiable factors and processes more proximal to dropout during treatment, may be needed. Trial registration: ClinicalTrials.gov identifier: NCT02874131.

Association between abnormal default mode network homogeneity and sleep disturbances in major depressive disorder

BackgroundSleep disturbance is a common comorbidity of major depressive disorder (MDD). However, network homogeneity (NH) changes of the default mode network (DMN) in MDD with sleep disturbances are unclear.AimsThe purpose...

Epistasis in neurotransmitter receptors linked to posttraumatic stress disorder and major depressive disorder comorbidity in traumatized Chinese.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) comorbidity occurs through exposure to trauma with genetic susceptibility. Neuropeptide-Y (NPY) and dopamine are neurotransmitters associated with anxiety and stress-related psychiatry through receptors. We attempted to explore the genetic association between two neurotransmitter receptor systems and the PTSD-MDD comorbidity. Four groups were identified using latent profile analysis (LPA) to examine the patterns of PTSD and MDD comorbidity among survivors exposed to earthquake-related trauma: low symptoms, predominantly depression, predominantly PTSD, and PTSD-MDD comorbidity. NPY2R (rs4425326), NPY5R (rs11724320), DRD2 (rs1079597), and DRD3 (rs6280) were genotyped from 1,140 Chinese participants exposed to earthquake-related trauma. Main, gene-environment interaction (G × E), and gene-gene interaction (G × G) effects for low symptoms, predominantly depression, and predominantly PTSD were tested using a multinomial logistic model with PTSD-MDD comorbidity as a reference. The results demonstrated that compared to PTSD-MDD comorbidity, epistasis (G × G) NPY2R-DRD2 (rs4425326 × rs1079597) affects low symptoms (β = -0.66, OR = 0.52 [95% CI: 0.32-0.84], p = 0.008, pperm = 0.008) and predominantly PTSD (β = -0.56, OR = 0.57 [95% CI: 0.34-0.97], p = 0.037, pperm = 0.039), while NPY2R-DRD3 (rs4425326 × rs6280) impacts low symptoms (β = 0.82, OR = 2.27 [95% CI: 1.26-4.10], p = 0.006, pperm = 0.005) and predominantly depression (β = 1.08, R = 2.95 [95% CI: 1.55-5.62], p = 0.001, pperm = 0.001). The two G × G effects are independent. NPY and dopamine receptor genes are related to the genetic etiology of PTSD-MDD comorbidity, whose specific mechanisms can be studied at multiple levels.