Linking head and heart health: the association between psychiatric outcomes for patients with major depressive disorder and myocardial ischemia - a systematic review.

INTRODUCTION: The development of depression after myocardial infarction is associated with a 2- to 2.5-fold increased risk of all-cause mortality, cardiovascular mortality, and cardiovascular events. The objective of this study was to investigate, through a broad search of the literature, whether major depression is associated with worse psychiatric outcomes in middle-aged patients with myocardial ischemia. METHODS: An extensive search for studies on the association between major depression and myocardial ischemia was conducted in the PubMed, Embase, PsycINFO, and Web of Science databases. Randomized clinical trials of middle-aged patients with myocardial ischemia and concomitant depressive symptoms were included. RESULTS: The 14 articles included in this systematic review did not confirm an association between myocardial ischemia and depression with worse psychiatric outcomes in middle-aged patients. However, worse cardiovascular outcomes have been observed in patients with depression after myocardial infarction. CONCLUSIONS: The findings of this study suggest that major depression increases cardiovascular risk in patients after acute myocardial infarction, possibly because of a more pronounced increase in inflammatory markers. REGISTRATION: This systematic review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) under the number CRD: 511650.

Associations between C-reactive protein and individual symptoms of depression in a lower-middle income country.

BACKGROUND: Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs). AIMS: We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms. METHOD: This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or <3 mg/L) and individual depressive symptoms measured using the Hamilton Depression Rating Scale. Descriptive statistics and regression were used to assess treatment response for inflammation-associated symptoms. RESULTS: High plasma CRP (≥3 mg/L) was detected in 87% (n = 146) of participants. Early night insomnia (odds ratio 2.33, 95% CI 1.16-5.25), early morning waking (odds ratio 2.65, 95% CI 1.29-6.38) and psychic anxiety (odds ratio 3.79, 95% CI 1.39-21.7) were positively associated, while gastrointestinal (odds ratio 0.38, 95% CI 0.14-0.86) and general somatic symptoms (odds ratio 0.34, 95% CI 0.14-0.74) were negatively associated with inflammation. Minocycline, but not simvastatin, improved symptoms positively associated with inflammation. CONCLUSIONS: The prevalence of inflammation in this LMIC sample with TRD was higher than that reported in high income countries. Insomnia and anxiety symptoms may represent possible targets for personalised treatment with immunomodulatory agents in people with elevated CRP. These findings require replication in independent clinical samples.

History of Peripartum Depression Moderates the Association Between Estradiol Polygenic Risk Scores and Basal Ganglia Volumes in Major Depressive Disorder.

BACKGROUND: The neurobiological differences between women who have experienced a peripartum episode and those who have only had episodes outside of this period are not well understood. METHODS: 64 parous female patients with major depressive disorder that have either a positive (n=30) or negative (n=34) history of peripartum depression (PPD) underwent MRI acquisition to obtain structural brain images. An independent two-sample t-test comparing patients with and without a history of PPD was performed using voxel-based morphometry analysis (VBM). Additionally, polygenic risk scores (PRSs) for estradiol were calculated and a moderation analysis was conducted between 3 estradiol PRSs and PPD history status on extracted cluster volumes using IBM SPSS PROCESS macro. RESULTS: The VBM analysis identified larger grey matter volumes in bilateral clusters encompassing the putamen, pallidum, caudate, and thalamus in patients with PPD history compared to patients without a history. The moderation analysis identified a significant interaction of 2 estradiol PRSs and PPD history on grey matter cluster volumes with a positive effect in PPD women and a negative effect in women with no history of PPD. CONCLUSIONS: Our findings demonstrate that women who have experienced a peripartum episode are neurobiologically distinct from women who have no history of PPD in a cluster within the basal ganglia, an area important for motivation, decision-making, and emotional processing. Furthermore, we show that the genetic load for estradiol has a differing effect in this area based on PPD status which supports the claim that PPD is associated with sensitivity to sex steroid hormones.

Differential effects of lifetime stressors on major depressive disorder severity: a longitudinal community-based cohort study.

BACKGROUND: Stressors across the lifespan are associated with the onset of major depressive disorder (MDD) and increased severity of depressive symptoms. However, it is unclear how lifetime stressors are related to specific MDD subtypes. The present study aims to examine the relationships between MDD subtypes and stressors experienced across the lifespan while considering potential confounders. METHODS: Data analyzed were from the Zone d'Épidémiologie Psychiatrique du Sud-Ouest de Montréal (N = 1351). Lifetime stressors included childhood maltreatment, child-parent bonding, and stressful life events. Person-centered analyses were used to identify the clusters/profiles of the studied variables and multinomial logistic regression analyses were performed to examine the relationships between stressors and identified MDD subtypes. Intersectional analysis was applied to further examine how distal stressors interact with proximal stressors to impact the development of MDD subtypes. RESULTS: There was a significant association between proximal stressors and melancholic depression, whereas severe atypical depression and moderate depression were only associated with some domains of stressful life events. Additionally, those with severe atypical depression and melancholic depression were more likely to be exposed to distal stressors such as childhood maltreatment. The combinations of distal and proximal stressors predicted a greater risk of all MDD subtypes except for moderate atypical depression. CONCLUSIONS: MDD was characterized into four subtypes based on depressive symptoms and severity. Different stressor profiles were linked with various MDD subtypes. More specific interventions and clinical management are called to provide precision treatment for MDD patients with unique stressor profiles and MDD subtypes.

Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection.

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD.

Neurophysiological activity following gains and losses among young adults with non-suicidal self-injury: An ERP study.

OBJECTIVE: Non-suicidal self-injury (NSSI) is an increasingly concerning issue that is linked to a range of mental health problems. However, little is known about the potential neurophysiological mechanisms underlying risk decision-making in Major depressive disorder (MDD) patients with NSSI-the present study aimed to fill this important literature gap. METHODS: A total of 81 MDD patients (with NSSI: n = 40, without NSSI: n = 41) and 44 matched healthy controls (HC) underwent a modified version of the Iowa Gambling Task (IGT) while an electroencephalogram was recorded. Feedback-related negativity (FRN) and P300 were examined during the feedback stage of the risky decision-making process. RESULTS: Behavioural findings revealed that individuals diagnosed with MDD displayed a greater tendency to make risky decisions compared to the control group. Furthermore, MDD patients with NSSI demonstrated a significantly more negative ΔFN (i.e., the difference in neural response to losses compared to gains) than those without NSSI. Further, NSSI patients showed a larger difference ΔFN (loss minus gain), which was associated with enhanced impulsivity. CONCLUSIONS: Collectively, the findings suggest that there is an altered processing of risky decision-making in the electrophysiology of patients with MDD who engage in NSSI. The ΔFN may serve as a psychophysiological marker indicating risk for NSSI.

Sex differences in insomnia and hypersomnia complaints during major depressive episode: Results from a national sample.

BACKGROUND: Sex differences in sleep disturbances during major depressive episodes (MDE) have been suggested. This study compares the prevalence, sociodemographic characteristics, and psychiatric comorbidity associated with sleep complaints specific to each sex among adults with MDE. These findings are crucial for precise diagnosis, personalized treatment, and improved clinical outcomes. METHODS: In a large nationally representative prospective survey, we used multi-adjusted logistic regression models including sociodemographic characteristics, psychiatric comorbidity, and depression severity to examine whether associations differ between men and women. RESULTS: Among women, 93.3 % reported at least one type of sleep complaints (i.e., trouble falling asleep, early morning awakening or hypersomnia) while 91.0 % of men did, with respectively 78.3 % and 77.2 % of insomnia complaints, and 46.2 % and 41.3 % of hypersomnia complaints. Women with sleep complaints were more likely to be black, with lower individual incomes, have histrionic personality disorder or a specific phobia. Conversely, men with sleep complaints were more likely to have a lifetime diagnosis of mania spectrum disorder, generalized anxiety disorder, drug use disorder, as well as dependent and schizotypal personality disorders. Surprisingly, being "never married" has emerged as a protective factor against sleep complaints in women, while posing as a risk factor in men compared to other marital statuses. Differences and specificities were also noted concerning subtypes of insomnia and hypersomnia complaints. LIMITATIONS: The cross-sectional design means the associations found do not imply causality. CONCLUSIONS: These findings provide insights into the complex relationship between sleep and depression in men and women, highlighting the need for personalized interventions.

Exploring cariprazine as a treatment option for varied depression symptom clusters.

Major depressive disorder (MDD) is among the most prevalent psychiatric conditions and a leading cause of disability worldwide. MDD presents a diverse range of symptoms that significantly impact personal, societal, and economic dimensions. Despite the availability of numerous antidepressant treatments (ADTs) targeting different molecular mechanisms, a substantial proportion of patients experience inadequate response, presenting a considerable challenge in MDD management. As a result, adjunctive strategies, particularly involving atypical antipsychotics, are often employed to enhance treatment efficacy. Cariprazine, a D2/D3 partial agonist, is distinguished from other atypical antipsychotics by its selective action on the D3 receptor and its modulation of 5-HT1A, 5-HT2A, and alpha 1B receptors. This distinctive pharmacological profile warrants investigation into its potential effectiveness and tolerability across various symptom domains of MDD, including pleasure, interest, and motivation; mood and suicidality; sleep and appetite; fatigue; psychomotor activity and anxiety; and cognitive function. Preliminary evidence from animal studies and clinical trials suggests that cariprazine may improve motivation, anhedonia, and cognitive function symptoms. Cariprazine shows promise in alleviating mood-related symptoms, though its impact on anxiety and its effects on agitation and psychomotor retardation remains uncertain. Cariprazine may be particularly beneficial for patients with MDD exhibiting anhedonia, cognitive deficits, and possibly fatigue and hypersomnia. Evaluating cariprazine's efficacy across these symptom domains could reveal patterns that support more personalized treatment approaches for depression. Further research is essential to elucidate the role of cariprazine as an adjunctive therapy for adults with major depressive disorder who have an inadequate response to antidepressant monotherapy.

The therapeutic alliance in blended versus face-to-face cognitive behavioral therapy for adolescents and young adults with a depressive disorder.

Introduction: A depressive disorder during adolescence is a serious and disabling disorder, which has a high impact on the development of adolescents. Blended treatment, combining online and face-to-face sessions, is effective and can reduce some of the barriers for adolescents to use mental health care. There is a lack of knowledge about whether therapeutic alliance is established in blended treatment for adolescents and young adults suffering from a depressive disorder. This study examines whether the quality of the therapeutic alliance differs when cognitive behavior therapy (CBT) is delivered in combination with online intervention (b-CBT) compared to solely face-to-face (FtF-CBT) and the extent to which a stronger therapeutic alliance is associated with better treatment outcome. Methods: A pragmatic quasi-experimental design was used. Data collected within two separate studies were combined. A total of 85 participants (80 % female), aged 13-22 (mean = 16.63, SD = 1.92) were recruited within mental health care institutions and diagnosed with a depressive disorder (using K-SADS). Assessments were done at pre-treatment (T0), after five weeks (T1), after ten weeks (T2), post-treatment (T3) and one to four weeks after treatment (T4) and included measures of depressive symptomatology (CDI-2). The therapeutic alliance was measured at T1, T2 and T3 by the TASC. t-tests for independent samples were used to test differences in therapeutic alliance rates between b-CBT and FtF-CBT at post-treatment. A linear growth model for depressive symptoms based on five time points with Latent Growth Curve Analysis (LGCA) was used to test whether the therapeutic alliance is associated with depressive symptoms. Results: No differences in therapeutic alliance between b-CBT and FtF-CBT were found on either client-rated or therapist-rated therapeutic alliance. For both intervention groups, no significant association between the therapeutic alliance and depressive outcome was found. Discussion: This study shows that providing part of CBT using an online environment does not have a negative impact on the therapeutic alliance. In contrast to earlier research, no association was found between the therapeutic alliance and therapy outcome in neither the b-CBT nor the FtF-CBT intervention.

Psilocybin for major depressive disorder: a systematic review of randomized controlled studies.

Objectives: The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD). Methods: A systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs). Results: Five RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2-13%) and the control group (4-21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache. Conclusion: Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs.

Treatment for Depression in Patients Who Have Suffered from Early Life Stress.

BACKGROUND: People with Major Depressive Disorder (MDD) are far more likely to suffer from Early Life Stress (ELS) than the average population. This typically increases severity of symptoms, and often leads to treatment resistance. This study set out to examine which treatments work best to treat depression in patients who have suffered from ELS, as well as possible interactions between ELS and antidepressant effects in therapies. METHOD: A literature review was conducted in July 2020 using the databases Embase, PsychInfo, and MEDLINE. The search looked for clinical trials treating MDD with psychotherapies and pharmacotherapies with patients who suffered from ELS. Data regarding demographics, comorbidities, measurement tools, and outcomes (generally response rates and remission) were extracted. The data was compared according to treatment types. RESULTS: Cognitive Behavioural Therapy (CBT) had the best evidence for treating MDD in people with ELS. There was some mixed evidence for Interpersonal Therapy, SSRIs, and SNRIs as suitable treatments for MDD. There was also very promising but limited evidence for Cognitive Behavioural Analysis of System Therapy and combination treatments (pharmacotherapy and psychotherapy together). Nefazodone (a SARI) had the weakest evidence. CONCLUSIONS: CBT was the most effective treatment for MDD with ELS. However, more research needs to be conducted to ascertain a proper hierarchy of treatments, particularly with combination treatments.

Iodine Deficiency as a Risk Factor for Postpartum Depressive Disorder in Women.

Nutritional support is considered as one of the components of disease-modifying therapy for postpartum depressive disorder. Such nutrients include iodine, which is an important trace element in the development and functioning of the central nervous system. The brief review presents updated knowledge about the relationship of iodine deficiency with the development and severity of postpartum depressive disorders in women, based on the analysis and generalization of the results of domestic and international studies.

Efficacy of racemic ketamine or esketamine monotherapy for reducing suicidal ideation in uni- or bipolar depression: a systematic review and meta-analysis.

The current systematic review and meta-analysis examined the effect of racemic ketamine or esketamine on suicidal ideation in individuals with uni- or bipolar depression. We searched the MEDLINE, Embase, Central, PsycINFO, and Web of Science databases to identify randomized controlled trials that examined the effect of racemic ketamine or esketamine monotherapy on suicidal ideation (SI) in individuals with uni- or bipolar depression. The two monotherapies were compared; the primary outcome was the rate of remission of SI, and the secondary outcome was the SI score. The risk ratio was used as an effect size measure for binary variables, while the standardized mean difference was used as an effect size measure for continuous variables. Our meta-analysis included 13 randomized controlled trials involving 1,1109 individuals with uni- or bipolar depression. Patients receiving racemic ketamine monotherapy had a significantly higher acute SI remission rate than those receiving placebo or midazolam (RR = 2.06, 95% CI 1.47 to 2.91, P < 0.0001). Racemic ketamine also led to significantly lower SI scores than placebo or midazolam (SMD = -0.36, 95% CI -0.71 to -0.01, P = 0.04). The evidence for the treatment of SI with esketamine was inconsistent. The pooled effect sizes for long-term anti-SI effects did not reveal significant differences between therapies. Our study indicated the efficacy of racemic ketamine monotherapy for rapidly and transiently reducing SI in individuals with uni- or bipolar depression, but the efficacy of racemic ketamine monotherapy against long-term suicidal ideation remains unclear. There is not -sufficient evidence to support the anti-suicidal effects of esketamine monotherapy.Protocol registration: Prospero registration number: CRD42023434380.

Association between TNF-α & IL-6 level changes and remission from depression with duloxetine treatment.

PURPOSE/AIM OF THE STUDY: The pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment. MATERIALS AND METHODS: MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks. RESULTS: Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks. Conclusions: These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment.

Identifying genetic variants associated with side effects of antidepressant treatment: A systematic review.

Major Depressive Disorder (MDD) is one of the most prevalent neurobiological disorders globally. Antidepressant medications are the first-line treatment for managing symptoms. However, over time, pharmacotherapy has been linked to several challenges, primarily due to the wide array of side effects that often reduce patient adherence to treatment. The literature suggests that these side effects may be influenced by polymorphisms in genes related to the pharmacokinetics and pharmacodynamics of antidepressants. Thus, this systematic review aimed to identify studies that investigated the association between genetic variants and side effects resulting from antidepressant treatment in individuals with MDD. Original articles indexed in the electronic databases Cochrane Library, EMBASE, MEDLINE via PubMed, and Scopus were identified. A total of 55 studies were included in the review, and data regarding the outcomes of interest were extracted. Due to the exploratory nature of the review, a narrative/descriptive synthesis of the results was performed. The risk of bias was evaluated using the Joanna Briggs Institute's tools, tailored to the design of each study. Polymorphisms in 35 genes were statistically associated with the development of side effects. A subsequent Protein-Protein Interaction Network analysis helped elucidate the key biological pathways involved in antidepressant side effects, with a view toward exploring the potential application of pharmacogenetic markers in clinical practice.

Antidepressants account for the causal effect of major depressive disorder on type 2 diabetes.

BACKGROUND: Patients with major depressive disorder (MDD) face an elevated risk of type 2 diabetes (T2D). However, the contribution of the disease itself versus the side effects of antidepressants to this increased risk remains unclear. OBJECTIVE: This study aimed to investigate the overall and independent effects of MDD and exposure to antidepressants on T2D risk. METHODS: Summary genome-wide association study datasets were utilized for the Mendelian randomization (MR) and multivariable MR (MVMR) analyses, including ones for MDD (N = 500,199), antidepressants (N = 175,161), and T2D (N = 933,970). Bayesian colocalization analysis was used to reveal shared genetic variation between MDD, antidepressants, and T2D. RESULTS: We found that both MDD (OR: 1.15, CI: 1.03-1.30, P = 0.016) and antidepressants (OR: 1.37, CI: 1.22-1.53, P = 2.75E-08) have overall causal effects on T2D. While T2D was associated with the risk of antidepressant use (OR: 1.08, CI: 1.06-1.11, P = 8.80E-10), but not with the risk of MDD (OR: 1.00, CI: 0.98-1.01, P = 0.661). Our MVMR analysis showed that the use of antidepressants is associated with higher risks of T2D (OR: 1.21, CI: 1.07-1.37, P = 7.19E-04), while MDD is not linked to the risk of T2D (OR: 1.01, CI: 0.86-1.18, P = 0.799). Colocalization analysis identified two shared genetic loci between antidepressants and T2D. CONCLUSIONS: The elevated T2D risk in MDD patients is chiefly caused by antidepressant use. These findings emphasize the importance of considering the impact of antidepressants on metabolic health in individuals with MDD.

Integration patterns of functional brain networks can predict the response to abdominal acupuncture in patients with major depressive disorder.

Abdominal acupuncture has definite efficacy for major depressive disorder (MDD). Our study examined how abdominal acupuncture regulates the integration within and between brain networks of MDD patients by neuroimaging and whether this functional integration can predict the efficacy. Forty-six female MDD patients were randomly divided into a fluoxetine + real acupuncture group (n = 22) and a fluoxetine + sham acupuncture group (n = 24). The differences in functional magnetic resonance imaging data in the intra- and inter-network functional connectivity (FC) of the default mode network (DMN), affective network (AN), salience network (SN), and cognitive control network (CCN) between the two groups were analyzed. The FCs in brain regions with the inter-group differences and support vector regression were used to predict the efficacy of abdominal acupuncture. Our results showed: that the intra- and inter-network FCs of DMN, AN, SN, and CCN could be changed by abdominal acupuncture. Using the baseline FCs within AN and DMN or AN-DMN as characteristics, combined with support vector regression, could better predict the efficacy of acupuncture. Our study suggests that abdominal acupuncture could treat MDD by regulating the integration of the functional networks DMN, AN, SN, and CCN. The baseline FCs within the DMN and AN or between them could be used as neural markers for predicting the efficacy of abdominal acupuncture.

The burden of mental health issues in Behçet's disease: implications for patient quality of life.

INTRODUCTION: Depression and anxiety are among the most prevalent mental health conditions in Brazil. Both are associated with poor quality of life (HRQoL) and challenges in disease management for chronic illnesses, including Behçet's disease (BD). This study aimed to evaluate depression, anxiety, and HRQoL in BD patients from a non-endemic area. RESEARCH DESIGN AND METHODS: This case-control study included adult BD patients from Brazilian tertiary center and healthy controls (HC). All patients fulfilled the ISG and ICBD diagnostic criteria. Depression, anxiety and quality of life were assessed using BDI, HADS, SF-36, and physical capacity with the HAQ. RESULTS: We enrolled 58 BD patients (60% female, mean age 46.1) and 96 HC (74% female, mean age 44). High rates of depression and anxiety were observed in BD patients, correlating with disease activity, younger age, absence of a partner, shorter disease duration, and lower income. BD patients showed significant HRQoL restrictions, particularly in physical and emotional roles, compared to HC. Longer disease duration was correlated with better HRQoL. CONCLUSION: High rates of depression and anxiety were observed in BD patients, negatively impacting HRQoL, particularly in those with higher disease activity. Further study and clinical attention are warranted to enhance patient care and outcomes.

Identification of multimodal brain imaging biomarkers in first-episode drugs-naive major depressive disorder through a multi-site large-scale MRI consortium data.

BACKGROUND: Major depressive disorder (MDD) is a severe and common mental illness. The first-episode drugs-naive MDD (FEDN-MDD) patients, who have not undergone medication intervention, contribute to understanding the biological basis of MDD. Multimodal Magnetic Resonance Imaging can provide a comprehensive understanding of brain functional and structural abnormalities in MDD. However, most MDD studies use single-modal, small-scale MRI data. And several multimodal studies of MDD are limited to simple linear combinations of functional and structural features. METHODS: We screened a large sample of FEDN-MDD patients and healthy controlsmultimodal MRI data. Extracting the fractional amplitude of low-frequency fluctuations (fALFF) feature from functional magnetic resonance imaging and the gray matter volume (GMV) feature from structural magnetic resonance imaging. The mCCA-jICA method was used to integrate these two modal features to investigate the functional-structural co-variation abnormalities in MDD. To validate the stability of the extracted functional-structural covariant abnormalities features, we apply them to identify FEDN-MDD patients. RESULTS: The results show that compared to healthy controls, FEDN-MDD patients exhibit joint group-discriminative independent component and modality-specific group-discriminative independent component, suggesting functional-structural covariant abnormalities in MDD patients. Using lightGBM classifier, we achieve a classification accuracy of 99.84 %. LIMITATION: We use GMV and fALFF for multimodal fusion shows promise, but requires further validation with other datasets and exploration of additional multimodal features. CONCLUSIONS: This may indicate that multimodal fusion features can effectively explore information between different modalities and can accurately identify FEDN-MDD patients, suggesting their potential as multimodal brain imaging biomarkers for MDD.

Protocol for a randomized controlled trial: exercise-priming of CBT for depression (the CBT+ trial).

BACKGROUND: Depression is a leading cause of disability worldwide, and treatments could be more effective. Identifying methods to improve treatment success has the potential to reduce disease burden dramatically. Preparing or "priming" someone to respond more effectively to psychotherapy (e.g., cognitive behavioral therapy [CBT]) by preceding sessions with aerobic exercise, a powerful neurobiological activator, could enhance the success of the subsequently performed therapy. However, the success of this priming approach for increasing engagement of working mechanisms of psychotherapy (e.g., increased working alliance and behavioral activation) has yet to be formally tested. METHODS: The CBT + trial will be a parallel-arm randomized controlled trial that will recruit 40 adult participants with DSM-5 diagnosed depression (verified with clinical interview) via referrals, mass emails, local flyers, and social media posts. Participants will be randomized to an ActiveCBT or CalmCBT condition. The ActiveCBT group will receive an 8-week CBT intervention primed with 30 min of moderate-intensity aerobic exercise (cycling on a stationary bike at a 13 rating of perceived exertion). The CalmCBT group will receive the same 8-week CBT intervention while resting for 30 min before CBT (i.e., cycling vs no cycling is the only difference). The primary outcome measures will be mean working alliance (assessed with the client version of the Working Alliance Inventory-Short Revised) and mean behavioral activation (self-reported Behavioral Activation for Depression Scale) recorded at each of the 8 therapy sessions. Secondary outcomes include evaluation of state anhedonia and serum brain-derived neurotrophic factor before the active/calm conditions, between the condition and therapy, and after the therapy. Additional exploratory analyses will evaluate group differences in algorithm-generated ratings of therapist-participant interactions via the Lyssn platform. DISCUSSION: The novel approach of priming CBT with moderate-intensity aerobic exercise evaluated in a randomized controlled trial (CBT + trial) has the potential to demonstrate the usefulness of exercise as an augmentation strategy that improves working mechanisms of therapy and overall treatment outcomes for adults with depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT06001346 . Registered on August 21, 2023.