Daily stress reactivity and risk appraisal mediates childhood parental abuse predicting adulthood psychopathology severity: An 18-year longitudinal mediation analysis.

Identifying mechanisms of childhood abuse-adulthood psychopathology relations could facilitate preventive efforts, but most prior studies used cross-sectional or two-wave designs and did not test the effects of childhood maternal and paternal abuse separately. Our 18-year three-wave study thus determined if Wave 2 daily stress reactivity and risk appraisal severity mediated Wave 1 retrospectively-reported childhood maternal and paternal abuse on Wave 3 generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD), alcohol (AUD), and substance use disorder (SUD) self-rated symptom severity. Longitudinal structural equation modeling was employed, adjusting for Wave 1 psychopathology severity. Higher childhood maternal and paternal abuse consistently predicted greater future daily stress reactivity and risk appraisal, and these mediators subsequently predicted increased GAD, MDD, and PD, but not AUD and SUD severity. Daily stress reactivity and risk appraisal consistently mediated the pathways between childhood maternal and paternal abuse predicting heightened adulthood GAD, MDD, and PD (Cohen's d = 0.333-0.888) but not AUD and SUD severity. Mediation effect sizes were stronger for childhood maternal (24.5-83.0 %) than paternal (19.5-56.0 %) abuse as the predictor. The latent interaction between Wave 1 childhood maternal and paternal abuse did not moderate the effect of Wave 1 maternal or paternal abuse on any Wave 3 adulthood psychopathology severity through Wave 2 daily stress reactivity and risk appraisal. Our research emphasizes the urgent requirement for continuous evaluation and intervention initiatives in trauma-informed care, both in inpatient and outpatient treatment settings.

Molecular mechanisms underlying structural plasticity of electroconvulsive therapy in major depressive disorder.

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.

Too little or too much: nonlinear relationship between sleep duration and daily affective well-being in depressed adults.

BACKGROUND: In addition to having higher negative affect and lower positive affect overall, depressed individuals exhibit heightened affective reactivity to external stimuli than non-depressed individuals. Sleep may contribute to day-to-day fluctuations in depressed individuals, given that sleep disturbance is a common symptom of depression. Yet, little is known about changes in daily affect as a function of nightly sleep duration in depressed adults and non-depressed adults. The current study examined whether and how naturally-occurring sleep duration is associated with negative and positive affect, and how these associations differ between depressed vs. non-depressed adults. METHODS: Data were drawn from the second wave of the National Study of Daily Experiences (NSDE), a daily diary project of the Midlife in the United States (MIDUS) study. The sample of 2,012 adults (Mage=56.5; 57% female; 84% white) completed eight-day diary interviews via telephone on their daily experiences including nightly sleep duration and negative and positive affect. They also completed assessments of the Composite International Diagnostic Interview-Short form, and depressed status was determined based on DSM-III. Multilevel regression models with linear, quadratic, and cubic terms of sleep duration examined the nonlinear relationship between nightly sleep duration and daily affect. Interaction terms with depression status were added to examine differences between depressed and non-depressed adults. RESULTS: Depressed adults exhibited significant and greater fluctuations in daily affect as a function of nightly sleep duration than non-depressed adults. Specifically, the degree of decrease in positive affect and increase in negative affect was greater when depressed adults slept 2 or more hours less or longer than their usual sleep hours. Non-depressed adults exhibited relatively stable daily affect regardless of their nightly sleep hours. CONCLUSIONS: Sleep duration is nonlinearly associated with affect in daily lives of depressed adults, highlighting that both having too little sleep and excessive sleep are associated with adverse daily affective well-being. Implementing sleep interventions to promote an appropriate sleep duration may help improve daily affect among depressed adults.

Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis.

Background: Little is known about the prevalence of cellular senescence among immune cells (i.e., immune cells expressing senescence markers, iSCs) nor is there a gold-standard to efficiently measure iSCs. Major depressive disorder (MDD) in older adults has been associated with many hallmarks of senescence in whole blood, leukocytes, and plasma, supporting a strong connection between iSCs and MDD. Here, we investigated the prevalence and phenotype of iSCs in older adults with MDD. Using a single-cell phenotypic approach, circulating immune cells were examined for iSC biomarkers and their relationship to depression and inflammation. Results: PBMCs from older adults with MDD (aged 69.75 ± 5.23 years) and healthy controls (aged 71.25 ± 8.8 years) were examined for immune subset distribution and senescence biomarkers (i.e., lack of proliferation, senescence-associated heterochromatin foci (SAHF), and DNA damage). Dual-expression of SAHF and DNA damage was categorized by low, intermediate, and high expression. A significant increase in the number of high expressing total PBMCs (p = 0.01), monocytes (p = 0.008), a trending increase in the number of high expressing CD4 T cells (p = 0.06) was observed overall in those with MDD. There was also a significantly lower proportion of intermediate expressing cells in monocytes and CD4 T cells in MDD (p = 0.01 and p = 0.05, respectively). Correlation analysis revealed associations between iSCs and mRNA expression of factors related to SASP and immune cell function. Conclusion: MDD is associated with increased senescent cell biomarkers in immune cell populations delineated by distinct levels of SAHF and DNA damage. Inflammatory markers might serve as potent indicators of iSC burden in MDD.

MicroRNAs as Diagnostic Biomarkers and Predictors of Antidepressant Response in Major Depressive Disorder: A Systematic Review.

Despite the hardships of major depressive disorder (MDD), biomarkers for the diagnosis and pharmacological management of this condition are lacking. MicroRNAs are epigenetic mechanisms that could provide promising MDD biomarkers. Our aim was to summarize the findings and provide validation for the selection and use of specific microRNAs as biomarkers in the diagnosis and treatment of MDD. A systematic review was conducted using the PubMed/Medline, Cochrane, PsycINFO, Embase, and LILACS databases from March 2022 to November 2023, with clusters of terms based on "microRNA" and "antidepressant". Studies involving human subjects, animal models, and cell cultures were included, whereas those that evaluated herbal medicines, non-pharmacological therapies, or epigenetic mechanisms other than miRNA were excluded. The review revealed differences in the expression of various microRNAs when considering the time of assessment (before or after antidepressant treatment) and the population studied. However, due to the heterogeneity of the microRNAs investigated, the limited size of the samples, and the wide variety of antidepressants used, few conclusions could be made. Despite the observed heterogeneity, the following microRNAs were determined to be important factors in MDD and the antidepressant response: mir-1202, mir-135, mir-124, and mir-16. The findings indicate the potential for the use of microRNAs as biomarkers for the diagnosis and treatment of MDD; however, more homogeneous studies are needed.

The (cost-)effectiveness of early intervention (MBT-early) versus standard protocolized treatment (CBT) for emerging borderline personality disorder in adolescents (the EARLY study): a study protocol for a randomized controlled trial.

BACKGROUND: Although clinical guidelines prioritize the treatment of depression and anxiety in young persons, there is accumulating evidence that the presence of symptoms of borderline personality disorder (BPD) is associated with the limited effectiveness of these standard treatments. These findings stress the need for interventions addressing early-stage BPD in young people with presenting symptoms of anxiety and depressive disorders. The aim of this study is to investigate the (cost-)effectiveness of an early intervention programme for BPD (MBT-early) compared to first-choice psychological treatment for depression and anxiety according to Dutch treatment guidelines (CBT), in adolescents with either depression, anxiety, or both, in combination with early-stage BPD. METHODS: This study is a multi-centre randomized controlled trial. A total of 132 adolescents, presenting with either depression, anxiety, or both and significant BPD features will be randomized to either MBT-early or CBT. The severity of BPD, symptoms of depression and anxiety, personality, social and academic functioning, and quality of life will be assessed at baseline, end of treatment, and at 12-, 18-, and 24-month follow-up, along with medical costs and costs of productivity losses for cost-effectiveness analyses. DISCUSSION: This study will provide an empirical evaluation of the potential surplus value of early intervention in young people for whom treatment oriented at common mental disorders like anxiety and depression may be insufficient given their underlying personality problems. TRIAL REGISTRATION: Netherlands Trial Register, NL9569. Registered on June 15, 2021.

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

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

Feasibility, Acceptability, and Preliminary Efficacy of a Smartphone App-Led Cognitive Behavioral Therapy for Depression Under Therapist Supervision: Open Trial.

BACKGROUND: Major depressive disorder affects approximately 1 in 5 adults during their lifetime and is the leading cause of disability worldwide. Yet, a minority receive adequate treatment due to person-level (eg, geographical distance to providers) and systems-level (eg, shortage of trained providers) barriers. Digital tools could improve this treatment gap by reducing the time and frequency of therapy sessions needed for effective treatment through the provision of flexible, automated support. OBJECTIVE: This study aimed to examine the feasibility, acceptability, and preliminary clinical effect of Mindset for Depression, a deployment-ready 8-week smartphone-based cognitive behavioral therapy (CBT) supported by brief teletherapy appointments with a therapist. METHODS: This 8-week, single-arm open trial tested the Mindset for Depression app when combined with 8 brief (16-25 minutes) video conferencing visits with a licensed doctoral-level CBT therapist (n=28 participants). The app offers flexible, accessible psychoeducation, CBT skills practice, and support to patients as well as clinician guidance to promote sustained engagement, monitor safety, and tailor treatment to individual patient needs. To increase accessibility and thus generalizability, all study procedures were conducted remotely. Feasibility and acceptability were assessed via attrition, patient expectations and feedback, and treatment utilization. The primary clinical outcome measure was the clinician-rated Hamilton Depression Rating Scale, administered at pretreatment, midpoint, and posttreatment. Secondary measures of functional impairment and quality of life as well as maintenance of gains (3-month follow-up) were also collected. RESULTS: Treatment credibility (week 4), expectancy (week 4), and satisfaction (week 8) were moderate to high, and attrition was low (n=2, 7%). Participants self-reported using the app or practicing (either on or off the app) the CBT skills taught in the app for a median of 50 (IQR 30-60; week 4) or 60 (IQR 30-90; week 8) minutes per week; participants accessed the app on an average 36.8 (SD 10.0) days and completed a median of 7 of 8 (IQR 6-8) steps by the week 8 assessment. The app was rated positively across domains of engagement, functionality, aesthetics, and information. Participants' depression severity scores decreased from an average Hamilton Depression Rating Scale score indicating moderate depression (mean 19.1, SD 5.0) at baseline to a week 8 mean score indicating mild depression (mean 10.8, SD 6.1; d=1.47; P<.001). Improvement was also observed for functional impairment and quality of life. Gains were maintained at 3-month follow-up. CONCLUSIONS: The results show that Mindset for Depression is a feasible and acceptable treatment option for individuals with major depressive disorder. This smartphone-led treatment holds promise to be an efficacious, scalable, and cost-effective treatment option. The next steps include testing Mindset for Depression in a fully powered randomized controlled trial and real-world clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05386329; https://clinicaltrials.gov/study/NCT05386329?term=NCT05386329.

Brain alterations in adolescents with first-episode depression who have experienced adverse events: evidence from resting-state functional magnetic resonance imaging.

Introduction: Adverse life events constitute primary risk factors for major depressive disorder (MDD), influencing brain function and structure. Adolescents, with their brains undergoing continuous development, are particularly susceptible to enduring impacts of adverse events. Methods: We investigated differences and correlations among childhood trauma, negative life events, and alterations of brain function in adolescents with first-episode MDD. The study included 23 patients with MDD and 19 healthy controls, aged 10-19 years. All participants underwent resting-state functional magnetic resonance imaging and were assessed using the beck depression inventory, childhood trauma questionnaire, and adolescent self-rating life events checklist. Results: Compared with healthy controls, participants with first-episode MDD were more likely to have experienced emotional abuse, physical neglect, interpersonal relationship problems, and learning stress (all p' < 0.05). These adverse life events were significantly correlated with alterations in brain functions (all p < 0.05). Discussion: This study contributes novel evidence on the underlying process between adverse life events, brain function, and depression, emphasizing the significant neurophysiological impact of environmental factors.

Cannabis use and mood disorders: a systematic review.

Background: Problematic cannabis use is highly prevalent among people with mood disorders. This underscores the need to understand the effects of cannabis and cannabinoids in this population, especially considering legalization of recreational cannabis use. Objectives: We aimed to (1) systematically evaluate cross-sectional and longitudinal studies investigating the interplay between cannabis use, cannabis use disorder (CUD), and the occurrence of mood disorders and symptoms, with a focus on major depressive disorder (MDD) and bipolar disorder (BD) and; (2) examine the effects of cannabis on the prognosis and treatment outcomes of MDD and BD. Methods: Following PRISMA guidelines, we conducted an extensive search for English-language studies investigating the potential impact of cannabis on the development and prognosis of mood disorders published from inception through November 2023, using EMBASE, PsycINFO, PubMed, and MEDLINE databases. Results: Our literature search identified 3,262 studies, with 78 meeting inclusion criteria. We found that cannabis use is associated with increased depressive and manic symptoms in the general population in addition to an elevated likelihood of developing MDD and BD. Furthermore, we observed that cannabis use is linked to an unfavorable prognosis in both MDD or BD. Discussion: Our findings suggest that cannabis use may negatively influence the development, course, and prognosis of MDD and BD. Future well-designed studies, considering type, amount, and frequency of cannabis use while addressing confounding factors, are imperative for a comprehensive understanding of this relationship. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023481634.

Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

Temporal binding and sense of agency in major depression.

Background: Alterations in the experience of controlling oneself and one's environment are of high relevance to understanding the psychopathology of depression. This study investigated the relationship between Temporal Binding for action-event sequences, sense of agency, self-efficacy and symptom severity in Major Depressive Disorder. Method: We employed the Sense of Agency Scale (SoAS) and the General Self-Efficacy Scale (GSE) to assess explicit Sense of Agency and self-efficacy in a group of 42 persons diagnosed with Major Depressive Disorder (MDD) [20 identifying as female, 19 as male; mean age 37.8 years (± 13.3)] and 40 control persons without a psychiatric diagnosis (CG) [22 identifying as female, 20 as male; mean age 38.0 years ( ± 13.3)]. Depressive symptom severity was measured using the BDI-II. We additionally performed a temporal binding paradigm as a potential correlate to Sense of Agency. Participants partook in a time estimation task judging three intervals (250ms, 450ms, 650ms) while either observing or causing stimulus presentations. The underestimation of intervals following intentional actions causing stimulus presentations (compared to merely observing the stimulus presentation) is interpreted as temporal binding. Results: SoAS scores demonstrated an inverse correlation with depressive symptoms (CG: p=.032, R2=.113; MDD: p<.001, R2=.260) and a positive correlation with GSE scores (CG: p<.001, R2=.379; MDD: p<.001, R2=.254). We found distinct differences in temporal binding between healthy participants and the Major Depressive Disorder group without significant correlation between temporal binding and the SoAS or GSE scores. The data suggest group differences in time estimation particular pertaining to time intervals involving intentional action and increasingly complex multisensory stimuli. Discussion: We investigated parameters of subjective control, namely Sense of Agency and Self Efficacy. Here, we were able to reveal their inverse relationship with depressive symptoms in patients with major depressive disorder, highlighting a profound experience of loss of control with increasing symptom load. Deficits in experiencing control, particularly involving intentional motor actions (and more complex multisensory stimuli), appear to be more pronounced in Major Depressive Disorder, involving not only negative self-efficacy expectations but also an altered Sense of Agency and temporal binding. Temporal binding and SoAS scores did not correlate, adding to the growing evidence that the two measures may not be directly related. We propose that future research be directed at this contiguous relationship between Sense of Agency and Self Efficacy in Major Depressive Disorder.

Differential modulation of resting-state functional connectivity between amygdala and precuneus after acute physical exertion of varying intensity: indications for a role in affective regulation.

Introduction: Physical activity influences psychological well-being. This study aimed to determine the impact of exercise intensity on psychological well-being and alterations in emotion-related brain functional connectivity (FC). Methods: Twenty young, healthy, trained athletes performed a low- and high-intensity interval exercise (LIIE and HIIE) as well as a control condition in a within-subject crossover design. Before and after each condition, Positive And Negative Affect Scale (PANAS) was assessed as well as resting-state functional MRI (rs-fMRI). Voxel-wise FC was examined for bilateral amygdala seed region to whole-brain and emotion-related anatomical regions (e.g., insula, temporal pole, precuneus). Data analyses were performed using linear mixed-effect models with fixed factors condition and time. Results: The PANAS Positive Affect scale showed a significant increase after LIIE and HIIE and a significant reduction in Negative Affect after the control condition. In rs-fMRI, no significant condition-by-time interactions were observed between the amygdala and whole brain. Amygdala-precuneus FC analysis showed an interaction effect, suggesting reduced post-exercise anticorrelation after the control condition, but stable, or even slightly enhanced anticorrelation for the exercise conditions, especially HIIE. Discussion: In conclusion, both LIIE and HIIE had positive effects on mood and concomitant effects on amygdala-precuneus FC, particularly after HIIE. Although no significant correlations were found between amygdala-precuneus FC and PANAS, results should be discussed in the context of affective disorders in whom abnormal amygdala-precuneus FC has been observed.

Graded exercise with motion style acupuncture therapy for a patient with failed back surgery syndrome and major depressive disorder: a case report and literature review.

Effective treatment of failed back surgery syndrome (FBSS) remains challenging despite urgent medical attention requirements. Depression is a contributing factor to the development and poor prognosis of FBSS, and vice versa. We report the case of a patient with FBSS and major depressive disorder (MDD) treated with graded exercise combined with motion-style acupuncture therapy (MSAT). A 53-year-old male veteran who had undergone lumbar discectomy and laminectomy with instrumented fusion was admitted to the hospital with re-current back pain and radiative pain in the left leg. The effects of failed surgery triggered MDD as a comorbidity. After a six-week routine treatment without remarkable improvement, a three-week program of graded exercise with MSAT was applied. The numeric rating scale (NRS) and short form-36 (SF-36) were used to assess low back pain with radiating leg pain, and daily functioning levels, respectively. The voluntary walking distance of the patients was measured. To analyze the therapeutic effects and other applications of the intervention, we surveyed clinical trials using MSAT or graded exercise therapy (GET). Three weeks of graded exercise with MSAT reduced physical and mental functional disabilities (SF-36, physical component: 15.0 to 37.2, mental component: 21.9 to 30.1) as well as the intensity of low back pain and/or radiative leg pain (NRS: 50 to 30). Furthermore, as the therapeutic intensity gradually increased, there was a significant corresponding increase in daily walking distance (mean daily walking distance, the first week vs. baseline, second, and third week, 3.05 ± 0.56: 2.07 ± 0.79, 4.27 ± 0.96, and 4.72 ± 1.04 km, p = 0.04, p = 0.02, and p = 0.003, respectively). Three randomized controlled trials of GET were included, all showing statistically significant antidepressant effects in the diseased population. Graded exercise with MSAT may be an effective rehabilitative therapy for patients with FBSS and MDD who have impaired daily routines.

Associations between breakfast skipping and outcomes in neuropsychiatric disorders, cognitive performance, and frailty: a Mendelian randomization study.

BACKGROUND: Prior studies have identified a correlation between breakfast skipping and a heightened risk of mental health issues. This investigation aimed to employ a Two-Sample Mendelian Randomization (MR) approach to explore the potential causal links between breakfast skipping and various psychiatric, neurological disorders, cognitive performance, and frailty. METHODS: Utilizing data from genome-wide association studies within European demographics, this research scrutinized the association between breakfast habits and several neuropsychiatric conditions and physical health outcomes, including Alzheimer's disease (AD), Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), Major Depressive Disorder (MDD), Narcolepsy, Insomnia, cognitive performance, and frailty. In this MR analysis, the Inverse Variance Weighted (IVW) method was primarily utilized for evaluation. Outcomes were reported as Odds Ratios (OR) and regression coefficients (ß), and underwent validation through False Discovery Rate (FDR) corrections, thereby offering a rigorous evaluation of the effects of breakfast habits on both mental and physical health dimensions. RESULTS: Findings demonstrate a significant causal link between skipping breakfast and an increased risk of ADHD (OR = 2.74, 95%CI: 1.54-4.88, PFDR = 0.003) and MDD (OR = 1.7, 95%CI: 1.22-2.37, PFDR = 0.005). Conversely, no substantial causal associations were identified between breakfast skipping and AD, BD, narcolepsy, or insomnia (PFDR > 0.05). Moreover, a notable causal relationship was established between skipping breakfast and a reduction in cognitive performance (ß = -0.16, 95%CI: -0.29-0.04, PFDR = 0.024) and an increase in frailty (ß = 0.29, 95%CI: 0.12-0.45, PFDR = 0.003). CONCLUSION: The MR analysis reveals that skipping breakfast is associated with an increased risk of ADHD, MDD, decreased cognitive performance, and greater frailty, while showing no associations were found with AD, BD, narcolepsy, or insomnia. These findings warrant further investigation into the underlying mechanisms and emphasize the importance of regular breakfast consumption for mental and physical well-being.

The Potential Role of Aripiprazole Augmentation for Major Depressive Disorder with Anxious Distress in Naturalistic Treatment Setting.

Objective: : This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice. Methods: : Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved. Results: : The changes of primary endpoint HAMA (t = 5.731, -4.6, p = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, -3.4, p ＜ 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, -0.9, t = 1.821, p = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, -0.4, p ＜ 0.001) scores were also significantly improved during the study. No significant adverse events were observed. Conclusion: : This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Defining "High Recurrence" of Depressive Episodes for Predicting Diagnostic Conversion from Major Depressive Disorder to Bipolar Disorder: A 5-year Retrospective Study.

Objective: This study determined the threshold for recurrent depressive episodes that predicted conversion from major depressive disorder (MDD) to bipolar disorder (BD). Methods: We retrospectively reviewed the medical records of 296 patients diagnosed with MDD for a minimum of 5 years in two university hospitals. We examined their the Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses and detailed clinical information at the initial admission and yearly assessments after discharge to establish the threshold for recurrent depressive episodes indicating a risk of diagnostic conversion from MDD to BD. Optimal cut-offs were derived using receiver operating characteristic (ROC) curves. Results: ROC curve analysis revealed that more than four recurrent depressive episodes was indicative of potential diagnostic conversion from MDD to BD (area under the curve, 0.604; sensitivity, 0.353; specificity, 0.855; positive predictive value, 0.421; negative predictive value, 0.816). Conclusion: These findings suggest that the best predictor of conversion from MDD to BD is more than four recurrent depressive episodes. Our findings have the potential to enhance diagnostic accuracy and treatment efficiency. To validate our results, longitudinal prospective studies are necessary.

Auditory P50 Sensory Gating Alterations in Major Depressive Disorder and their Relationship to Clinical Symptoms.

Cognitive deficits in depression are pervasive and include impairments in attention and higher-order functions but the degree to which low-level sensory processes are affected is unclear. The present work examined event-related potential (P50 and N100) features of auditory sensory gating (i.e., the ability to inhibit P50/N100 responses to redundant stimuli) and their relationship to depressive symptoms, including ruminations and dysfunctional attitudes. In 18 patients with major depressive disorder (MDD) and 18 healthy volunteers, auditory sensory gating was measured using a paired-stimulus paradigm yielding ratio (rP50, rN100) and difference (dP50, dN100) gating indices, which reflected amplitude reductions from first (S1) to second (S2) stimulus. Patients with MDD exhibited diminished rP50 and dP50 gating scores and delayed S1-N100 latencies compared to healthy volunteers. These measures were positively associated with ruminative thoughts, negative attitudes and degree of depression. Study findings implicate aberrant sensory processing in depressed patients that is related to severity of maladaptive thinking.

Depressive symptom trajectories with prolonged rTMS treatment.

BACKGROUND: A prolonged repetitive transcranial magnetic stimulation (rTMS) treatment course could be beneficial for some patients experiencing major depressive episodes (MDE). We identified trajectories of rTMS response in depressive patients who received an extended rTMS treatment course and sought to determine which trajectories achieved the greatest benefit with a prolonged treatment course. METHOD: We applied group-based trajectory modeling to a naturalistic dataset of depressive patients receiving a prolonged course of sequential bilateral rTMS (up to 51 treatment sessions) to the dorsolateral prefrontal cortex. Trajectories of the PHQ-9 with extended treatment courses were characterized, and we explored the association between baseline clinical characteristics and group membership using multinomial logistic regression. RESULTS: Among the 324 study participants, four trajectories were identified: "linear response, extended course" (N = 73; 22.5%); "nonresponse" (N = 23; 7.1%); "slowed response" (N = 159; 49.1%); "rapid response, standard treatment length" (N = 69; 21.3%). Only the "linear response, extended course" group showed considerable clinical improvement after receiving additional rTMS treatments. Greater baseline depressive symptoms were associated with linear response and non-response. CONCLUSION: Our results confirmed the distinctive response trajectories in depressive patients receiving rTMS and further highlighted that prolonged rTMS treatment courses may be beneficial for a subset of patients with higher initial symptom levels and linear early treatment response.

Prevalence of major depressive disorder and post-traumatic stress disorder among first-time sleep center attendees.

BACKGROUND: Sleep disorders and psychiatric disorders stand in a bidirectional relationship. Sleep complaints are prominent in populations with psychiatric disorders, especially amongst people with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Consultations at sleep clinics offer opportunities to screen psychiatric disorders and to propose primary psychiatric care. METHODS: This descriptive study was conducted on 755 patients making their first visit to sleep clinic, with 574 seeking consultation for suspected obstructive sleep apnoea-hypopnoea syndrome (OSAHS), 139 for complaints of insomnia, and 42 for complaints of hypersomnia. The results of 387 screening scales for MDD (BDI-II) and 403 for TSPT (PCL-5) were compared according to the reason given for the consultation. RESULTS: In the whole group, 12.1 % of patients presented a positive MDD screening and 4.9 % for PTSD. Among patients presenting with insomnia, 19.8 % had a positive screening for MDD, as compared to 9.3 % in patients presenting with suspected OSAHS (p = 0.02). Regarding PTSD, 9.7 % of patients seeking consultation because of insomnia had a positive screening, compared to 2.9 % among patients with suspected OSAHS (p = 0.03). Among patients with a positive screening for MDD, 40.5 % were not receiving antidepressant or mood stabilizer treatment. CONCLUSION: Positive screening for MDD and PTSD are frequent in patients who attend sleep centers, especially amongst those presenting with insomnia. Nearly half of the patients with positive screening for MDD or PTSD were not receiving a dedicated pharmacological treatment. These figures emphasize systematic screening for psychiatric disorders in sleep clinics.