Background: Research suggests that male-specific psychotherapy approaches for major depressive disorder (MDD) that consider traditional masculinity ideologies (TMI) may achieve improved treatment efficacy and reduced therapy dropout. However, studies examining male-specific psychotherapy for MDD or specific therapy aspects remain lacking. Methods: An anonymous online study on men\'s mental health examined 152 self-reporting mentally distressed cisgender men (Mage = 25.5 ± 9.1) from German-speaking countries of Europe. After completing baseline assessments (T1) of state self-esteem, state shame, positive/negative affect, depressive symptoms, and TMI, men were randomly assigned to read either a male-specific (MSP) or a cognitive behavioral therapy-oriented (CBT) psychoeducation text for MDD. Immediately afterwards, participants rated its usefulness and completed follow-up assessments (T2). Results: Men in the MSP condition showed a stronger decrease in shame and negative affect as compared to men in the CBT-psychoeducation condition. Furthermore, in the MSP condition, prototypical depression symptoms tended to increase as compared to the CBT-psychoeducation, whereas male-typical externalizing depression symptoms tended to decrease. Conclusion: MSP for MDD may help depressed men feel less ashamed about their MDD and experience less negative affect about their condition than CBT-psychoeducation. Furthermore, MSP for MDD may elicit a shift from male-typical externalizing depression symptoms to prototypical depression symptoms.

UNASSIGNED: Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment for drug-resistant major depressive disorder (MDD) patients. Since the success rate of rTMS treatment is about 50%-55%, it is essential to predict the treatment outcome before starting based on electroencephalogram (EEG) signals, leading to identifying effective biomarkers and reducing the burden of health care centers.
UNASSIGNED: To this end, pretreatment EEG data with 19 channels in the resting state from 34 drug-resistant MDD patients were recorded. Then, all patients received 20 sessions of rTMS treatment, and a reduction of at least 50% in the total beck depression inventory (BDI-II) score before and after the rTMS treatment was defined as a reference. In the current study, effective brain connectivity features were determined by the direct directed transfer function (dDTF) method from patients\' pretreatment EEG data in all frequency bands separately. Then, the brain functional connectivity patterns were modeled as graphs by the dDTF method and examined with the local graph theory indices, including degree, out-degree, in-degree, strength, out-strength, in-strength, and betweenness centrality.
UNASSIGNED: The results indicated that the betweenness centrality index in the Fp2 node and the δ frequency band are the best biomarkers, with the highest area under the receiver operating characteristic curve value of 0.85 for predicting the rTMS treatment outcome in drug-resistant MDD patients.
UNASSIGNED: The proposed method investigated the significant biomarkers that can be used to predict the rTMS treatment outcome in drug-resistant MDD patients and help clinical decisions.

BACKGROUND: Persons with Major Depressive Disorder (MDD), notably treatment-resistant depression (TRD), are differentially affected by type 2 diabetes mellitus and associated morbidity. Ketamine is highly efficacious in the treatment of adults living with MDD, notably TRD. Herein, we sought to determine the effect of ketamine on metabolic parameters in animal stress paradigms and human studies.
METHODS: We performed a comprehensive search on PubMed, OVID, and Scopus databases for primary research articles from inception to May 5, 2024. Study screening and data extraction were performed by two reviewers (S.W. and G.H.L.). Both preclinical and clinical studies were included in this review.
RESULTS: Results from the preclinical studies indicate that in experimental diabetic conditions, ketamine does not disrupt glucose-insulin homeostasis. Within adults with MDD, ketamine is associated with GLUT3 transporter upregulation and differentially affects metabolomic signatures. In adults with TRD, ketamine induces increased brain glucose uptake in the prefrontal cortex. Available evidence suggests that ketamine does not adversely affect metabolic parameters.
CONCLUSIONS: There are a paucity of clinical studies evaluating the effects of ketamine on glucose-insulin homeostasis in adults with MDD.
CONCLUSIONS: Our results indicate that ketamine is not associated with significant and/or persistent disruptions in metabolic parameters. Available evidence indicates that ketamine does not adversely affect glucose-insulin homeostasis. These results underscore ketamine\'s efficacy and safety as an antidepressant treatment that is not associated with metabolic disturbances commonly reported with current augmentation therapies.

Early-life adversity (ELA) is characterized by exposure to traumatic events during early periods of life, particularly involving emotional, sexual and/or physical adversities during childhood. Mental disorders are strongly influenced by environmental and lifestyle-related risk factors including ELA. However, the molecular link between ELA and the risk of an adult mental disorder is still not fully understood. Evidence is emerging that long-lasting changes in the epigenetic processes regulating gene expression, such as DNA methylation, play an important role in the biological mechanisms linking ELA and mental disorders. Based on a recent study, we analyzed the DNA methylation of a specific CpG site within the gene PXDN-cg10888111-in blood in the context of ELA across a set of psychiatric disorders, namely Borderline Personality Disorder (BPD), Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD), and its potential contribution to their pathogenesis. We found significant hypermethylation in mentally ill patients with high levels of ELA compared to patients with low levels of ELA, whereas cg10888111 methylation in healthy control individuals was not affected by ELA. Further investigations revealed that this effect was driven by the MDD cohort. Providing a direct comparison of cg10888111 DNA methylation in blood in the context of ELA across three mental disorders, our results indicate the role of PXDN regulation in the response to ELA in the pathogenesis of mental disorders, especially MDD. Further studies will be needed to validate these results and decipher the corresponding biological network that is involved in the transmission of ELA to an adult mental disorder in general.

Major depressive disorder (MDD) is a leading cause of disability worldwide. While traditional pharmacological treatments are effective for many cases, a significant proportion of patients do not achieve full remission or experience side effects. Nutritional interventions hold promise as an alternative or adjunctive approach, especially for treatment-resistant depression. This review examines the potential role of nutrition in managing MDD through addressing biological deficits and modulating pathways relevant to its pathophysiology. Specifically, it explores the ketogenic diet and gut microbiome modulation through various methods, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Numerous studies link dietary inadequacies to increased MDD risk and deficiencies in nutrients like omega-3 s, vitamins D and B, magnesium, and zinc. These deficiencies impact neurotransmitters, inflammation, and other biological factors in MDD. The gut-brain axis also regulates mood, stress response, and immunity, and disruptions are implicated in MDD. While medications aid acute symptoms, nutritional strategies may improve long-term outcomes by preventing relapse and promoting sustained remission. This comprehensive review aims to provide insights into nutrition\'s multifaceted relationship with MDD and its potential for developing more effective integrated treatment approaches.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment in major depressive disorder (MDD). However, intermittent theta-burst stimulation (iTBS) and rTMS protocols using 10 Hz stimulation frequency might differ in their effect on neuroplasticity and on clinical symptoms. This study compares the effect of iTBS and a novel 10 Hz-rTMS with shortened single session duration, on motor excitability and neuroplasticity and on clinical symptoms in MDD.
METHODS: 30 patients with MDD received either iTBS or the novel 10 Hz-rTMS daily over three weeks to the left dorsolateral prefrontal cortex. Before and after the interventions, motor excitability, short-latency intracortical inhibition and long-term-potentiation-like plasticity in the motor cortex and clinical symptoms were measured by use of transcranial magnetic stimulation.
RESULTS: After the intervention, the level of neuroplasticity increased and clinical symptoms of depression were reduced in both groups, though both effects were significantly stronger after the novel 10 Hz-rTMS. Importantly, the changes in neuroplasticity and clinical symptoms were correlated: the stronger neuroplasticity increased, the stronger was the improvement of clinical symptoms.
CONCLUSIONS: Short intervention period of 3 weeks. Clinical symptoms were measured by self-assessment only and are therefore preliminary.
CONCLUSIONS: The novel 10 Hz-rTMS is more effective in increasing neuroplasticity in MDD and potentially also in reducing clinical symptoms than iTBS. This might be due to a differential mode of action on neuroplasticity and to the stimulation frequency of 10 Hz (within the alpha range) being more suitable to reset the brain\'s activity and to support neuroplastic changes.

BACKGROUND: Childhood trauma (CT) and family functioning exert significant influences on the course and long-term outcome of major depressive disorder (MDD) and bipolar disorder (BD) patients. Hence, we examined the intricate relationship between CT, family function, and the severity of depressive episodes in MDD and BD patients.
METHODS: 562 patients with depressive episodes (336 MDD and 226 BD) and 204 healthy controls (HCs) were included in this retrospective study. The 17-item Hamilton Depression Rating Scale (HAMD-17), Childhood Trauma Questionnaire (CTQ), and Family Adaptability and Cohesion Evaluation Scale (FACES II-CV) were assessed. Pearson correlation analysis and mediation analysis were performed.
RESULTS: CT had both a direct and indirect impact on depression severity in MDD and BD groups. In MDD, family adaptability mediated the impact of all CT subtypes on depression severity (Effect = 0.113, [0.030, 0.208]). In BD, family cohesion played a mediating role between emotional neglect (EN) and HAMD-17 scores (Effect = 0.169, [0.008, 0.344]). Notable differences were observed in onset age, illness duration, episode frequency, family history, and CT subtypes between MDD and BD (P < 0.05).
CONCLUSIONS: This study has several limitations including recall bias, lack of objective family functioning measures, small sample size, and cross-sectional design.
CONCLUSIONS: Family functioning mediated the impact of CT on depressive symptoms severity in MDD and BD patients. MDD patients with a history of CT exhibited reduced family adaptability, while BD patients with a history of EN had weaker familial emotional bonds. Our findings highlighted the importance of family-focused preventive interventions in mitigating the long-term effects of CT.

UNASSIGNED: Major depressive disorder and schizophrenia have been hypothesized to be closely associated with cancer. However, the associations between these psychiatric conditions and the development of lung cancer remain uncertain. This study aimed to explore the causal relationship among major depressive disorder, schizophrenia, and the risk of lung cancer.
UNASSIGNED: Two-sample bidirectional/multivariable and mediation Mendelian randomization (MR) analyses were conducted. Genome-wide summary data on major depressive disorder (N=500,199) and schizophrenia (N=127,906) were utilized. Data on the risk of lung cancer (overall, adenocarcinoma, and squamous cell) were collected from a cohort of individuals of European ancestry (N=27,209). Three smoking-related behaviors (smoking initiation, pack years of smoking, and cigarettes smoked per day) were included in the multivariable and mediation MR analyses.
UNASSIGNED: Patients with schizophrenia had a significantly greater risk of developing lung cancer (odds ratio (OR) = 1.144, 95% confidence interval (95% CI): 1.048-1.248, P = 0.003). The number of cigarettes smoked per day partially mediated the relationship between schizophrenia and the overall risk of lung cancer (OR = 1.185, 95% CI: 1.112-1.264, P = 0.021, proportion of mediation effect: 61.033%). However, there is no reliable evidence indicating an association between major depressive disorder and the risk of lung cancer (overall, adenocarcinoma, and squamous cell cancer).
UNASSIGNED: The findings indicated an association between schizophrenia and an increased risk of lung cancer, with smoking served as a partial mediator. When smoking was included in the regression analysis, the explanatory power of schizophrenia diagnosis was reduced, suggesting that smoking may be an important causal contributor to lung cancer in this population. Given the high prevalence of smoking among individuals with schizophrenia, these results underscore the need for further research to explore the underlying mechanisms of smoking\'s impact. Consequently, greater emphasis should be placed on monitoring the respiratory health of individuals with schizophrenia and implementing early interventions to address smoking-related behaviors.

Treatment-resistant depression (TRD) is a significant challenge in psychiatric practice, affecting a substantial proportion of patients with major depressive disorder (MDD). Traditional treatment modalities often fall short, necessitating the exploration of alternative therapies. This literature review examines the combined use of Transcranial Magnetic Stimulation (TMS) and ketamine in treating TRD. The objective of this study is to evaluate the efficacy, safety, and potential synergies of combining TMS and ketamine in the treatment of TRD. A comprehensive literature search was conducted using PubMed and Google Scholar databases from 2014 to 2024. The search terms included combinations of \"Transcranial Magnetic Stimulation,\" \"Ketamine,\" \"Depression,\" \"Major Depressive Disorder,\" \"Treatment-Resistant Depression,\" and \"Combination.\" After screening for relevance and applying inclusion and exclusion criteria, six studies were selected for review, including three case reports, a retrospective study, a pilot study, and a review study. The selected studies demonstrated that the combination of TMS and ketamine resulted in substantial and sustained improvement in depressive symptoms for patients with TRD. Case reports and retrospective studies highlighted significant reductions in depression severity and improvements in psychosocial functioning. The combination therapy showed a higher efficacy compared to monotherapies of either TMS or ketamine alone. Notably, adverse effects were generally mild and transient, with no severe adverse events reported in most studies. In conclusion, the combination of TMS and ketamine presents a promising treatment modality for patients with TRD, offering significant improvements in depressive symptoms and better outcomes compared to traditional monotherapies. However, the heterogeneity in study designs and small sample sizes underline the need for larger, randomized controlled trials to establish standardized protocols and further validate these findings.

BACKGROUND: Major Depressive Disorder (MDD) affects 350 million people worldwide. Electroconvulsive therapy (ECT) is effective, yet research on cognitive assessments post-treatment is lacking. This study systematically reviews and meta-analyzes the effectiveness of cognitive assessment tools post-ECT to optimize MDD treatment.
METHODS: Following PRISMA guidelines, this review was pre-registered on PROSPERO (CRD42023470318). Searches were conducted across nine databases up to November 12, 2023. Quality assessment for Randomized Controlled Trials (RCTs) and quasi-experimental studies was performed using the Cochrane risk of bias tool, JBI critical appraisal tools, and the Jadad scale. Meta-analyses for short-term and long-term cognitive function involved 24 and 18 tools, respectively.
RESULTS: Thirty studies (20 RCTs and 10 quasi-experimental) involving 2462 MDD patients were evaluated. Results indicated no significant differences in overall short-term and long-term cognitive functions post-ECT. Short-term analysis showed impairments in memory, learning, and verbal abilities but improvements in attention and processing speed. Long-term analysis revealed enhancements in memory, learning, verbal, and visuospatial abilities compared to baseline. Based on GRADE classification, we recommend 11 tools for assessing acute cognitive function and 10 tools for chronic cognitive impairment. These tools demonstrated high reliability and validity, supporting their clinical use.
CONCLUSIONS: These findings provide critical evidence for future ECT clinical guidelines in managing MDD. The recommended tools can aid clinicians in adjusting ECT regimens, identifying early cognitive changes, and improving therapeutic outcomes in MDD treatment.