Bidirectionality of LF when the movie makes you sad: Effects of negative emotions on heart rate variability among patients with major depression.

OBJECTIVES: Heart rate variability (HRV) reflects the capacity to adapt to internal and environmental changes. Decreased HRV may indicate inadequate adaptive capacity. This study aims to investigate the relationship between the heart and brain's adaptive abilities, both at rest and when negative emotions are stimulated in depression. SUBJECTS AND METHODS: The study included 30 patients (20 female, 10 male) with major depression (mean age = 29.8 ± 7.8) and 30 healthy controls, all of whom had similar characteristics in terms of age and gender, selected through convenience sampling. The patients were drug-free at the time of the assessment. Holter recordings were obtained while subjects watched videos stimulating anger, fear, sadness, and a neutral video, and at rest, HRV parameters were calculated. To control for interindividual variability and account for paired sampling, linear mixed effects models were employed. RESULTS: Watching the 'sadness video' led to an increase in low frequency band (LF) [LF change (Control vs depression); Difference:-620.80 df:107 t:-2.093 P:0.039] and LF/high frequency band ratio (LF/HF) [LF/HF change (control vs depression group); Difference:-1.718 df:105 t:-2.374 P:0.020] in the depression group. The video led to a decrease in LF and LF/HF in the controls. Although the differences between the conditions and interactions with the group were significant, the effects were independent of depression severity. CONCLUSION: In depression, brain's regulatory effect on the heart differed from controls in the sadness condition, possibly due to increased arousal levels in subjects with depression and their inability to suppress sympathetic activity when a state of sadness is stimulated.

Can the DEX/CRH test or markers of oxidative stress distinguish work-related stress from major depressive disorder and normal controls?

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC). Also, we explored if the cortisol response of those patients interacted with robust markers of oxidative stress. Thirty inpatients with MDD and 23 outpatients with ED were recruited. Plasma cortisol and ACTH were sampled during a DEX-CRH test. The main outcome measure, area under the curve (AUC) for cortisol and ACTH, was compa-red between MDD vs. ED participants and a historical HC group. Secondary markers of oxidative stress urinary 8-oxodG and 8-oxoGuo; quality of sleep and psychometrics were obtained. Cortisol concentrations were higher in MDD and ED participants compared to HC, and no differences in AUC cortisol and ACTH were found between ED vs. MDD. Compared to ED, MDD participants had higher stress symptom severity and a lower sense of well-being. No differences in oxidative stress markers or quality of sleep between the groups were found. The result indicates that the patients with ED, like patients with MDD, are non-suppressors in DEX-CRH test and not hypocortisolemic as suggested.

What CBT Modules Work Best for Whom? Identifying Subgroups of Depressed Youths by Their Differential Response to Specific Modules.

Prior research suggests that the effects of specific cognitive-behavioral therapy (CBT) modules on symptom outcomes can be estimated. We conducted a study utilizing idiographic and nomothetic methods to clarify which CBT modules are most effective for youth depression, and for whom they are most effective. Thirty-five youths received modular CBT for depression. Interrupted time series models estimated whether the introduction of each module was associated with changes in internalizing symptoms, whereby significant symptom reduction would suggest a therapeutic response to the module. Regression models were used to explore whether participant characteristics predicted subgroups of youths based on their estimated response to certain types (e.g., cognitive) of modules, and whether group membership was associated with posttreatment outcomes. Thirty youths (86%) had at least one module associated with a significant change in internalizing symptoms from premodule delivery to postmodule delivery. The specific modules associated with these changes varied across youths. Behavioral activation was most frequently associated with symptom decreases (34% of youths). No participant characteristics predicted estimated response to module type, and group membership was not significantly associated with posttreatment outcomes. Youths display highly heterogeneous responses to treatment modules, indicating multiple pathways to symptom improvement for depressed youths.

Association of cancer and schizophrenia, major depression and bipolar disorder: A Mendelian randomization study.

BACKGROUND: Schizophrenia, bipolar disorder and major depression have been reported to be associated with some cancers. However, the magnitude of the causal relationship between them remains unclear. This study aims to explore the potential association between three major mental diseases and the risk of some cancers. METHODS: We performed the two-sample Mendelian randomization(MR) analysis using publicly available genome-wide association studies (GWAS) statistics to investigate the causal relationship between these three mental diseases and some common types of cancers, including breast cancer, ovarian cancer, lung cancer, colorectal cancer, bladder cancer, prostate cancer, thyroid cancer, pancreatic cancer, malignant melanoma and glioma. We obtained genetic association estimates for schizophrenia, bipolar disorder and depression from the Psychiatric Genomics Consortium.The genetic association estimates for cancers were obtained from the UK Biobank, the MRC-IEU consortium and the GliomaScan consortium. RESULTS: After correction for heterogeneity and horizontal pleiotropy, we detected suggestive evidence for the association between thyroid cancer and genetically predicted schizophrenia (OR = 1.543, 95% CI: 1.023-2.328, P = 0.039), and thyroid cancer and major depression (OR = 3.573, 95% CI: 1.068-11.953, P = 0.039). No evidence of causal effects of schizophrenia, major depression and bipolar disorder on other types of cancers. CONCLUSIONS: Our findings suggest the association of schizophrenia and major depression and the development of thyroid cancer.

Longitudinal Association between Stressful Life Events and Suicidal Ideation in Adults with Major Depression Disorder: The Mediating Effects of Insomnia Symptoms.

Stressful life events (SLEs) and suicidal ideation (SI) are prevalent in persons with major depression disorder (MDD). Less is known about the underlying role of insomnia symptoms in the association between SLEs and SI. This three-wave prospective cohort study sought to investigate the longitudinal association among SLEs, insomnia symptoms, and SI in persons with MDD. The study population included 511 persons with MDD (mean [SD] age, 28.7 [6.7] years; 67.1% were females). Generalized estimated equations (GEEs) were utilized to explore prospective association among exposure of SLEs, insomnia symptoms, and SI. Additionally, a structural equation model (SEM) was employed to estimate the longitudinal mediating effect of insomnia symptoms in the relationship between SLEs and SI. Our study demonstrated that cumulative SLEs were determined to be longitudinally associated with SI in persons with MDD. We further observed that the association between SLEs and SI was significantly mediated by insomnia symptoms. Clinicians assessing persons with MDD, especially those with the history of SLE, could carefully evaluate and promptly treat insomnia symptoms as part of personalized assessment of their depressive illness, thereby achieving early prevention and intervention for suicidal behaviors in persons with MDD.

T cell activation and lowered T regulatory cell numbers are key processes in severe major depressive disorder: Effects of recurrence of illness and adverse childhood experiences.

BACKGROUND: Major depressive disorder (MDD) is characterized by increased T helper (Th)1 polarization, T cell activation (e.g., CD71+ and CD40L+), and cannabinoid receptor type 2 bearing CD20+ B cells; and lower T regulatory (Treg) numbers. AIMS: To delineate the effects of adverse childhood experiences (ACEs) and recurrence of illness (ROI) on activated T and CB2-bearing B populations, and Tregs, including FoxP3 + CD152+, FoxP3 + GARP+, and FoxP3 + CB1+ cells. METHODS: We measured ROI, ACEs, the number of activated T cells, Tregs, and CD20 + CB2+ B cells, in 30 MDD patients and 20 healthy controls. RESULTS: A larger part of the variance in the depression phenome (40.8 %) was explained by increased CD20 + CB2+ and activated T cells, and lowered Tregs. ROI and lifetime suicidal behaviors were significantly and positively associated with CD20 + CB2+, CD3 + CD71+, CD3 + CD40L+, CD4 + CD71+, CD4 + CD40L+, and CD4HLADR+ numbers. ROI was significantly correlated with CD8 + CD40L+ numbers. The sum of ACEs was significantly associated with CD20 + CB2+, CD3 + CD40L+, CD4 + 40 L+ numbers, T cell activation (positively) and Treg (inversely) indices. One replicable latent vector could be extracted from activated T cells, lifetime and current suicidal behaviors, number of depressive episodes, and severity of depression, and 48.8 % of its variance was explained by ACEs. CONCLUSIONS: ACE-induced activation of T effector and cytotoxic cells and B cells with autoimmune potential, coupled with lowered Treg numbers are a key component of depression. The findings indicate that increasing ROI, the phenome of depression and suicidal behaviors, are caused by autoimmune processes, which are the consequence of ACEs and increasing sensitization of immune responses.

Factors Associated with High Parent- and Youth-Rated Irritability Score in Early-Onset Mood Disorders: A Cross-Sectional Study with the Affective Reactivity Index (ARI).

Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated with low versus high parent- and self-rated irritability using the affective reactivity index (ARI) in a sample of 289 adolescents diagnosed with a bipolar or a major depressive disorder. Bivariate analyses were followed by multilinear logistic regression model. Factors significantly and independently associated with high versus low parent-rated ARI score were: more severe emotional dysregulation and bipolar disorders diagnosis. Factors significantly and independently associated with high versus low self-rated ARI score were: lower children depression rating scale (CDRS-R) difficulty of having fun item score, greater children depression inventory (CDI-2) self-report score, more severe emotional dysregulation, and greater CDRS-R appetite disturbance item score. High parent-rated irritability was strictly related with a bipolar disorder diagnosis, whereas high youth-rated irritability was related to depressive phenotype characterized by appetite/food-intake dysregulation, mood lability, and less anhedonia and apathy.

The impact of family-genetic risk scores on social functioning in individuals affected with six major psychiatric and substance use disorders in a Swedish National Sample.

To examine whether the level of genetic risk in psychiatric disorders impacts the social functioning of affected individuals, we examine the relationship between genetic risk factors for major depression (MD), anxiety disorders (AD), bipolar disorder (BD), non-affective psychosis (NAP), alcohol use disorder (AUD), and drug use disorder (DUD) in disordered individuals and five adverse social outcomes: unemployment, residence in areas of social deprivation, social welfare, early retirement, and divorce. We examine all cases with registration for these disorders from 1995 to 2015 in individuals born in Sweden. Genetic risk was assessed by the family genetic risk score (FGRS) and statistical estimates by Cox proportional hazard models. High genetic risk was significantly and modestly associated with poorer social outcomes in 23 of 30 analyses. Overall, genetic risk for MD, AD, AUD, and DUD impacted social functioning more strongly in affected individuals than did genetic risk for BD and NAP. Social welfare had the strongest associations with genetic risk, and residence in areas of high deprivation had the weakest. In individuals suffering from psychiatric and substance use disorders, high levels of genetic risk impact not only clinical features but also diverse measures of social functioning.

Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.

Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis.

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy. Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study. Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38). Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.

Technical Report: Efficacy and Safety of Low-Intensity Transcranial Magnetic Stimulation in the Remission of Depressive Symptoms in Patients With Treatment-Resistant Depression in Mexico.

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that induces action potentials in the stimulated cortical area and has been approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). The prevalence of MDD in Mexico almost tripled after the COVID-19 pandemic. In this study, we evaluated the safety and therapeutic effects of low-intensity TMS (Li-TMS) - characterized by inducing electric currents below the action potential threshold on the cerebral cortex - in 41 subjects diagnosed with treatment-resistant depression (TRD). A Li-TMS device dispensed repetitive magnetic pulses at 30 mT for 60 minutes during 20 sessions (once daily from Monday to Saturday) with the theta burst pattern. Our results suggest that Li-TMS is a safe therapy with antidepressant effects, demonstrated by the decrease in Beck Depression Inventory (BDI) scores and lessening of depressive symptoms.

Genetically predicted major depression causally increases the risk of temporomandibular joint disorders.

Objective: Observational studies have reported that mental disorders are comorbid with temporomandibular joint disorder (TMD). However, the causal relationship remains uncertain. To clarify the causal relationship between three common mental illnesses and TMD, we conduct this Mendelian Randomization (MR) study. Methods: The large-scale genome-wide association studies data of major depression, bipolar disorder and schizophrenia were retrieved from the Psychiatric Genomics Consortium. The summary data of TMD was obtained from the Finn-Gen consortium, including 211,023 subjects of European descent (5,668 cases and 205,355 controls). The main approach utilized was inverse variance weighting (IVW) to evaluate the causal association between the three mental disorders and TMD. Five sensitivity analyses including MR-Egger, Maximum Likelihood, Weighted median, MR. RAPS and MR-PRESSO were used as supplements. We conducted heterogeneity tests and pleiotropic tests to ensure the robustness. Results: As shown by the IVW method, genetically determined major depression was associated with a 1.65-fold risk of TMD (95% CI = 1.10-2.47, p < 0.05). The direction and effect size remained consistent with sensitivity analyses. The odds ratios (ORs) were 1.51 (95% CI = 0.24-9.41, p > 0.05) for MR-Egger, 1.60 (95% CI = 0.98-2.61, p > 0.05) for Weighted median, 1.68 (95% CI = 1.19-2.38, p < 0.05) for Maximum likelihood, 1.56 (95% CI = 1.05-2.33, p < 0.05) for MR. RAPS, and 1.65 (95% CI = 1.10-2.47, p < 0.05) for MR-PRESSO, respectively. No pleiotropy was observed (both P for MR-Egger intercept and Global test >0.05). In addition, the IVW method identified no significant correlation between bipolar disorder, schizophrenia and TMD. Conclusion: Genetic evidence supports a causal relationship between major depression and TMD, instead of bipolar disorder and schizophrenia. These findings emphasize the importance of assessing a patient's depressive status in clinical settings.

Large Individual Differences in Functional Connectivity in the Context of Major Depression and Antidepressant Pharmacotherapy.

Clinical studies of major depression (MD) generally focus on group effects, yet interindividual differences in brain function are increasingly recognized as important and may even impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g., related to MD diagnosis and treatment response). Functional MRI data from 107 participants (63 female, 44 male) were collected at baseline, 2, and 8 weeks during which patients received pharmacotherapy (escitalopram, N = 68) and controls (N = 39) received no intervention. The unique contributions of different sources of variation were examined by calculating how much variance in functional connectivity was shared across all participants and sessions, within/across groups (patients vs controls, responders vs nonresponders, female vs male participants), recording sessions, and individuals. Individual differences and common connectivity across groups, sessions, and participants contributed most to the explained variance (>95% across analyses). Group differences related to MD diagnosis, treatment response, and biological sex made significant but small contributions (0.3-1.2%). High individual variation was present in cognitive control and attention areas, while low individual variation characterized primary sensorimotor regions. Group differences were much smaller than individual differences in the context of MD and its treatment. These results could be linked to the variable findings and difficulty translating research on MD to clinical practice. Future research should examine brain features with low and high individual variation in relation to psychiatric symptoms and treatment trajectories to explore the clinical relevance of the individual differences identified here.

Impact of subjective sleep quality on objective measures of neurocognitive dysfunction in patients with major depressive disorder.

Background: Sleep disturbances are prevalent in major depressive disorder (MDD). MDD and sleep disturbances are both linked to cognitive impairments. Studies exploring the mechanisms and impact of sleep disturbances on neurocognitive functioning in depressed patients are lacking and proper assessment and therapeutic interventions for sleep disturbances are not part of clinical management of MDD. Aim: We investigated the association between subjective sleep quality and neurocognitive dysfunction in patients with MDD. Materials and Methods: Patients with moderate MDD episode were matched and assigned to two groups with poor and good sleep quality. We used Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. To measure frontotemporally mediated cognitive functioning, following tests were administered: Wisconsin Card Sorting Test (WCST) and degraded continuous performance test (CPT-DS). Two-tailed independent samples t tests or Mann-Whitney U tests and Pearson's correlation coefficient were performed for the statistical analysis of sleep latency, sleep duration, overall sleep quality, CPT d' value, WCST correct answers, errors, and perseverative errors. Results: Participants with MDD and poor sleep quality performed worse on cognitive tests compared to patients with MDD and good sleep quality. Scores of subjective sleep on PSQI positively correlated with WCST errors (r (60) =0.8883 P = .001) and negatively correlated with WCST correct answers (r (60) = -.869 P = .001) and measures of CPT-DS d' value (r (60) = -.9355 P = .001). Conclusions: Poor sleep quality, notably sleep duration and sleep latency, worsens the neurocognitive impairments of MDD patients. As these impairments are found to be associated with treatment outcomes, sleep disturbances should be additionally assessed and treated in MDD episode.

TanhReLU -based convolutional neural networks for MDD classification.

Major Depression Disorder (MDD), a complex mental health disorder, poses significant challenges in accurate diagnosis. In addressing the issue of gradient vanishing in the classification of MDD using current data-driven electroencephalogram (EEG) data, this study introduces a TanhReLU-based Convolutional Neural Network (CNN). By integrating the TanhReLU activation function, which combines the characteristics of the hyperbolic tangent (Tanh) and rectified linear unit (ReLU) activations, the model aims to improve performance in identifying patterns associated with MDD while alleviating the issue of model overfitting and gradient vanishing. Experimental results demonstrate promising outcomes in the task of MDD classification upon the publicly available EEG data, suggesting potential clinical applications.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces depression-like phenotype.

The etiology of major depressive disorder (MDD) remains poorly understood. Our previous studies suggest a role for the aryl hydrocarbon receptor (AhR) in depression. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant, with a high AhR binding affinity, and an established benchmark for assessing AhR activity. Therefore, this study examined the effect of TCDD on depression-like behaviors. Female mice were fed standard chow or a high-fat diet (HFD) for 11 weeks, and their weight was recorded. Subsequently, they were tested for baseline sucrose preference and splash test grooming. Then, TCDD (0.1 µg/kg/day) or vehicle was administered orally for 28 days, and mice were examined for their sucrose preference and performances in the splash test, forced swim test (FST), and Morris water maze (MWM) task. TCDD significantly decreased sucrose preference, increased FST immobility time, and decreased groom time in chow-fed mice. HFD itself significantly reduced sucrose preference. However, TCDD significantly increased FST immobility time and decreased groom time in HFD-fed mice. A small decrease in bodyweight was observed only at the fourth week of daily TCDD administration in chow-fed mice, and no significant effects of TCDD on bodyweights were observed in HFD-fed mice. TCDD did not have a significant effect on spatial learning in the MWM. Thus, this study demonstrated that TCDD induces a depression-like state, and the effects were not due to gross lethal toxicity. This study further suggests that more studies should examine a possible role for AhR and AhR-active environmental pollutants in precipitating or worsening MDD.

Cognitive Behavioral Therapy and Hypnosis in the Treatment of Major Depressive Disorder: A Randomized Control Trial.

We investigated whether adding hypnosis to CBT (CBTH) improved treatment outcomes for MDD with a two-armed, parallel-treated, randomized-controlled trial using anonymous self-report and clinician-blinded assessments. Expectancy, credibility, and attitude to hypnosis were also examined. Participants (n = 66) were randomly allocated to 10-weekly sessions of group-based CBT or CBTH. LMM analyses of ITT and Completer data at post-treatment, six-month and 12-month follow-up showed that both treatments were probably efficacious but we did not find significant differences between them. Analyses of remission and response to treatment data revealed that the CBTH Completer group significantly outperformed CBT at 12-month follow-up (p = .011). CBTH also displayed significantly higher associations between credibility, expectancy and mood outcomes up to 12-month follow-up (all p < .05 or better), while attitude to hypnosis showed one significant association (r = -0.57, p < .05). These results suggest that hypnosis shows promise as an adjunct in the treatment of MDD but a larger sample size is required to fully test its merits.

Comparison of Dutch healthy eating and healthy eating indexes and anthropometry in patients with major depression with health subjects: a case-control study.

Background: Diseases and disorders related to mental health are spreading like other chronic diseases all around the world. Considering the role of food in the prevention and treatment of these disorders, including major depression, investigating the relationship between different food patterns and this disorder is of particular importance. The aim of this study was to compare Dutch healthy eating and healthy eating indexes and anthropometry in patients with major depression with healthy individuals. Methods: In this case-control study, the final analysis was performed on 67 men and 111 women with an age range of 20-30 years. Height (cm), weight (kg), food frequency questionnaire (FFQ), physical activity (MET-min/week), demographic and PHQ-9 questionnaires were taken from all participants. In the following, all the food ingredients and their components were extracted and used to calculate HEI-2015 and DHD. Statistical analysis was performed using SPSS software with independent t-test, logistic regression and chi-square. Results: It was found that people with major depression in this study were mostly women and occupied. The average HEI-2015 in healthy people and those with major depression was 58 and 54.3, respectively. Also, the average DHD in these people was 60.5 and 55, respectively. HEI-2015 and DHD had a significant negative correlation with depression score (r = -0.16, p-value = 0.03) (r = -0.19, p-value = 0.01). Also, in the logistic regression model, before and even after adjusting confounders, HEI-2015 and DHD had a reduced odds ratio in people suffering from major depression. The two groups did not differ significantly in terms of the average factors of height, weight and body mass index (BMI). Conclusion: It seems that HEI2015 and DHD have a significant relationship in reducing major depression. However, due to the small number of studies in this regard, especially in the field of DHD, the need for more studies seems necessary.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis.

BACKGROUND: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target. OBJECTIVE: The aim of this study was to gather blinded data exploring the efficacy of applying DBS to the BNST in patients with highly refractory depression. METHOD: Eight patients with chronic severe treatment-resistant depression underwent DBS to the BNST. A randomised, double-blind crossover study design with fixed stimulation parameters was followed and followed by a period of open-label stimulation. RESULTS: During the double-blind crossover phase, no consistent antidepressant effects were seen with any of the four stimulation parameters applied, and no patients achieved response or remission criteria during the blinded crossover phase or during a subsequent period of three months of blinded stimulation. Stimulation-related side effects, especially agitation, were reported by a number of patients and were reversible with adjustment of the stimulation parameters. CONCLUSIONS: The results of this study do not support the application of DBS to the BNST in patients with highly resistant depression or ongoing research utilising stimulation at this brain site. The blocked randomised study design utilising fixed stimulation parameters was poorly tolerated by the participants and does not appear suitable for assessing the efficacy of DBS at this location.