Alpha oscillation mediates the interaction between suicide risk and symptom severity in Major Depressive Disorder.

Objective: The aim of our study was to explore the relationship between changes in neural oscillatory power in the EEG, the severity of depressive-anxiety symptoms, and the risk of suicide in MDD. Methods: 350 MDD patients' demographic and clinical data were collected, and their depressive and anxious symptoms were evaluated using HDRS-17 and HAMA-14, along with a suicide risk assessment using the Nurses' Global Assessment of Suicide Risk (NGASR). EEG data were captured, processed, and analyzed to study brain activity patterns related to MDD. The participants were divided based on suicide risk levels, and statistical analyses, including chi-square, t-tests, Pearson's correlations were used to explore the associations between brain activity, symptom severity, and suicide risk. Closely related variables were identified and ultimately the optimal model was screened using stepwise regression analysis with a forward strategy, and mediation effects were further used to determine the possible interactions between the variables in the regression model. Results: The regression model showed a significant effect of HDRS-17 and alpha power of Medial Occipital Cortex (MOC) on suicide risk, with elevated HDRS-17 increasing suicide risk and elevated alpha power decreasing suicide risk. Mediation effect analyses showed that MOC alpha power partially mediated the effect of depression level on suicide risk, and that an increase in depression severity may lead to a decrease in MOC alpha power, while a decrease in MOC alpha power may lead to an increase in suicide risk. Conclusion: The severity of depression directly increases suicide risk, whereas higher alpha power in the MOC serves as a protective factor, reducing this risk. Notably, MOC alpha power not only directly impacts suicide risk but also mediates the effects of both depression severity and anxiety levels on this risk. Limitations: The relatively small sample size of this study may limit the representativeness of the overall MDD patient population and the detailed analysis of different subgroups. This study did not delve into the relationship between the severity of cognitive symptoms in MDD patients and suicide risk.

Antidepressant class and concurrent rTMS outcomes in major depressive disorder: a systematic review and meta-analysis.

Background: Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). Findings: 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of -0.65 [-0.98, -0.31], p = 0.0002, I2 = 66.1%), higher response (OR = 0.97 [0.50, 1.44], p < 0.0001, I2 = 25.33%) and remission rates (OR = 1.04 [0.55, 1.52], p < 0.0001, I2 = 0.00%) than medication with sham rTMS. No additive benefit was found for SNRIs with rTMS (SMD of 0.10 [-0.14, 0.34], p = 0.42, I2 = 0.00%; OR = 0.12 [-0.39, 0.62], p = 0.64, I2 = 0.00%; OR = -0.31 [-0.90, 0.28], p = 0.86, I2 = 39.9%). The overall risk of bias for the included studies ranged from low to high, with 1 study having a high risk of bias. Interpretation: The combination of rTMS with SSRIs, but not SNRIs, significantly reduced depression severity, increasing response and remission rates. Some analyses demonstrated high heterogeneity, which was influenced by an SSRI trial with a high effect size. Overall, these results suggest that not all antidepressant combination therapies are alike, and SSRIs should be considered when initiating rTMS. Funding: Donald T. Stuss Young Investigator Research Innovation Award from the Sandra Black Centre for Brain Resilience & Recovery and the Harquail Centre for Neuromodulation through the Sunnybrook Foundation.

Neural signatures of default mode network subsystems in first-episode, drug-naive patients with major depressive disorder after 6-week thought induction psychotherapy treatment.

Evidence indicates that the default mode network (DMN) plays a crucial role in the neuropathology of major depressive disorder (MDD). However, the neural signatures of DMN subsystems in MDD after low resistance Thought Induction Psychotherapy (TIP) remain incompletely understood. We collected functional magnetic resonance imaging data from 20 first-episode, drug-naive MDD and 20 healthy controls (HCs). The DMN was segmented into three subsystems and seed-based functional connectivity (FC) was computed. After 6-week treatment, the significantly reduced FCs with the medial temporal lobe memory subsystem in MDD at baseline were enhanced and were comparable to that in HCs. Changed Hamilton Depression Rating Scale scores were significantly related with changed FC between the posterior cingulate cortex (PCC) and the right precuneus (PCUN). Further, changed serotonin 5-hydroxytryptamine levels were significantly correlated with changed FCs between the PCC and the left PCUN, between the posterior inferior parietal lobule and the left inferior temporal gyrus, and between the retrosplenial cortex and the right inferior frontal gyrus, opercular part. Finally, the support vector machine obtained an accuracy of 67.5% to distinguish between MDD at baseline and HCs. These findings may deepen our understanding of the neural basis of the effects of TIP on DMN subsystems in MDD.

Factors influencing the tendency of residual symptoms in patients with depressive disorders: a longitudinal study.

BACKGROUND: Residual symptoms of depressive disorders are serious health problems. However, the progression process is hardly predictable due to high heterogeneity of the disease. This study aims to: (1) classify the patterns of changes in residual symptoms based on homogeneous data, and (2) identify potential predictors for these patterns. METHODS: In this study, we conducted a data-driven Latent Class Growth Analysis (LCGA) to identify distinct tendencies of changes in residual symptoms, which were longitudinally quantified using the QIDS-SR16 at baseline and 1/3/6 months post-baseline for depressed patients. The association between baseline characteristics (e.g. clinical features and cognitive functions) and different progression tendencies were also identified. RESULTS: The tendency of changes in residual symptoms was categorized into four classes: "light residual symptom decline (15.4%)", "residual symptom disappears (39.3%)", "steady residual symptom (6.3%)" and "severe residual symptom decline (39.0%)". We observed that the second class displayed more favorable recuperation outcomes than the rest of patients. The severity, recurrence, polypharmacy, and medication adherence of symptoms are intricately linked to the duration of residual symptoms' persistence. Additionally, clinical characteristics including sleep disturbances, depressive moods, alterations in appetite or weight, and difficulties with concentration have been identified as significant factors in the recovery process. CONCLUSIONS: Our research findings indicate that certain clinical characteristics in patients with depressive disorders are associated with poor recovery from residual symptoms following acute treatment. This revelation holds significant value in the targeted attention to specific patients and the development of early intervention strategies for residual symptoms accordingly.

The interaction between TMEM161B (rs768705) and paranoid personality traits in relation to the risk of major depressive disorder: Results form a longitudinal study of 7642 Chinese freshmen.

BACKGROUND: Rs768705 (TMEM161B) is one of the identified single nucleotide polymorphisms related to major depressive disorder (MDD). Paranoid personality traits are independently associated with the risk of MDD. This study aimed to investigate the interaction effect between rs768705 (TMEM161B) and paranoid personality traits on the new-onset risk of MDD in Chinese freshmen. METHODS: A longitudinal study was conducted among 7642 Chinese freshmen without lifetime MDD at baseline in 2018. 158 new-onset MDD cases were ascertained in 2019. DNA samples were extracted to detect the genotype of rs768705. The diagnostic and statistical manual of mental disorders-IV criteria were used to determine MDD and personality disorder traits. Multiplicative interaction was assessed by logistic regression models. Tomas Andersson's method for calculating biological interactions was used to estimate the additive interaction. RESULTS: Rs768705(AG) (OR = 1.88, 95 % CI: 1.24-2.83) and paranoid personality traits (OR = 3.68, 95 % CI: 2.57-5.26) were significantly associated with the risk of MDD. The multiplicative interaction model with the product term of rs768705 and paranoid personality trait traits had a significant interaction effect (OR = 4.20, 95 % CI:1.62-10.91). There was also a significant additive interaction effect (RR = 7.08, 95 % CI:4.31-11.65) for the incidence of MDD. Seventy seven percent patients among new MDD cases were attributed to the additive interaction effect between rs768705 and paranoid personality traits. CONCLUSIONS: Rs768705 (AG) may interact with paranoid personality traits to increase the incidence of MDD among Chinese college students. Schools and psychosocial health organizations should pay more attention to individuals with paranoid personality traits for MDD intervention and prevention.

The emergence of antidepressant drugs targeting GABAA receptors: A concise review.

Depression is among the most common psychiatric illnesses, which imposes a major socioeconomic burden on patients, caregivers, and the public health system. Treatment with classical antidepressants (e.g. tricyclic antidepressants and selective serotonine reuptake inhibitors), which primarily affect monoaminergic systems has several limitations, such as delayed onset of action and moderate efficacy in a relatively large proportion of depressed patients. Furthermore, depression is highly heterogeneus, and its different subtypes, including post-partum depression, involve distinct neurobiology, warranting a differential approach to pharmacotherapy. Given these shortcomings, the need for novel antidepressants that are superior in efficacy and faster in onset of action is fully justified. The development and market introduction of rapid-acting antidepressants has accelerated in recent years. Some of these new antidepressants act through the GABAergic system. In this review, we discuss the discovery, efficacy, and limitations of treatment with classic antidepressants. We provide a detailed discussion of GABAergic neurotransmission, with a special focus on GABAA receptors, and possible explanations for the mood-enhancing effects of GABAergic medications (in particular neurosteroids acting at GABAA receptors), and ultimately, we present the most promising molecules belonging to this family which are currently used in clinical practice or are in late phases of clinical development.

Novel insight into astrocyte-mediated gliotransmission modulates the synaptic plasticity in major depressive disorder.

Major depressive disorder (MDD) is a form of glial cell-based synaptic dysfunction disease in which glial cells interact closely with neuronal synapses and perform synaptic information processing. Glial cells, particularly astrocytes, are active components of the brain and are responsible for synaptic activity through the release gliotransmitters. A reduced density of astrocytes and astrocyte dysfunction have both been identified the brains of patients with MDD. Furthermore, gliotransmission, i.e., active information transfer mediated by gliotransmitters between astrocytes and neurons, is thought to be involved in the pathogenesis of MDD. However, the mechanism by which astrocyte-mediated gliotransmission contributes to depression remains unknown. This review therefore summarizes the alterations in astrocytes in MDD, including astrocyte marker, connexin 43 (Cx43) expression, Cx43 gap junctions, and Cx43 hemichannels, and describes the regulatory mechanisms of astrocytes involved in synaptic plasticity. Additionally, we investigate the mechanisms acting of the glutamatergic, gamma-aminobutyric acidergic, and purinergic systems that modulate synaptic function and the antidepressant mechanisms of the related receptor antagonists. Further, we summarize the roles of glutamate, gamma-aminobutyric acid, d-serine, and adenosine triphosphate in depression, providing a basis for the identification of diagnostic and therapeutic targets for MDD.

Status and trends of TMS research in depressive disorder: a bibliometric and visual analysis.

Background: Depression is a chronic psychiatric condition that places significant burdens on individuals, families, and societies. The rapid evolution of non-invasive brain stimulation techniques has facilitated the extensive clinical use of Transcranial Magnetic Stimulation (TMS) for depression treatment. In light of the substantial recent increase in related research, this study aims to employ bibliometric methods to systematically review the global research status and trends of TMS in depression, providing a reference and guiding future studies in this field. Methods: We retrieved literature on TMS and depression published between 1999 and 2023 from the Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) databases within the Web of Science Core Collection (WoSCC). Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps. Results: A total of 5,046 publications were extracted covering the period from 1999 to 2023 in the field of TMS and depression. The publication output exhibited an overall exponential growth trend. These articles were published across 804 different journals, BRAIN STIMULATION is the platform that receives the most articles in this area. The literature involved contributions from over 16,000 authors affiliated with 4,573 institutions across 77 countries. The United States contributed the largest number of publications, with the University of Toronto and Daskalakis ZJ leading as the most prolific institution and author, respectively. Keywords such as "Default Mode Network," "Functional Connectivity," and "Theta Burst" have recently garnered significant attention. Research in this field primarily focuses on TMS stimulation patterns, their therapeutic efficacy and safety, brain region and network mechanisms under combined brain imaging technologies, and the modulation effects of TMS on brain-derived neurotrophic factor (BDNF) and neurotransmitter levels. Conclusion: In recent years, TMS therapy has demonstrated extensive potential applications and significant implications for the treatment of depression. Research in the field of TMS for depression has achieved notable progress. Particularly, the development of novel TMS stimulation patterns and the integration of TMS therapy with multimodal techniques and machine learning algorithms for precision treatment and investigation of brain network mechanisms have emerged as current research hotspots.

Smoking as a mediator in the association between major depressive disorder and schizophrenia on lung cancer risk: a bidirectional/multivariable and mediation Mendelian randomization study.

Background & Aims: 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. Methods: 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. Results: 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). Conclusions: 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.

Gender differences in risk factors for suicide attempts among young, first-episode and drug-naive major depressive disorder patients with anxiety symptoms.

Background: Suicide attempts and anxiety are common commodities in patients with major depressive disorder (MDD), and suicide attempts are often associated with anxiety symptoms. Studies have found gender differences in several aspects of MDD; however, gender differences in suicide attempts in young first-episode and drug-naive (FEDN) MDD patients with anxiety remain unknown. This study aimed to investigate potential gender differences in the prevalence of suicide attempts and associated risk factors among young FEDN MDD patients with anxiety in a Chinese Han population. Methods: A cross-sectional study was conducted on 1289 young patients with FEDN MDD. Demographics, clinical characteristics, and biochemical parameters of patients were collected. Results: Suicide attempters accounted for 23.80% and 26.12% of male and female FEDN MDD patients with anxiety, respectively, with no significant gender differences. Binary logistic regression analyses showed that anxiety, clinical global impression severity, and thyroid peroxidase antibody significantly predicted suicide attempts in both male and female FEDN MDD patients with anxiety, while body mass index significantly predicted suicide attempts only in males, and psychotic symptoms predicted suicide attempts only in females. Conclusion: The present study represents the first large-scale investigation of gender differences in the prevalence of suicide attempts and related risk factors among young FEND MDD patients with anxiety in the Chinese Han population. The results indicate that risk factors associated with suicide attempts vary by gender among young FEND MDD patients with anxiety, although a comparable rate of suicide attempts was observed in both female and male patients.

Resting-State Alpha Activity in the Frontal and Occipital Lobes and Assessment of Cognitive Impairment in Depression Patients.

Background: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals. Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated. Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05). Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.

The role of psilocybin in depressive disorders.

Depression is a serious psychiatric disorder with a high incidence of morbidity and mortality and psilocybin with psychotherapy has emerged as a promising potential in the treatment of depressive disorders. A review of psilocybin use in patients with depressive disorders is presented.A search was conducted investigating the use of psilocybin in patients with depressive disorders and treatment resistant depression via PubMed/MEDLINE, EMBASE, and Google Scholar in October 2023; all publication types were permitted and limited for English-language. Keyword search terms included: "psilocybin" or "psychedelics" and "depression", or "major depressive disorder", or "treatment-resistant depression". Controlled and uncontrolled clinical trials utilizing psilocybin with psychological support for major depressive disorder and treatment-resistant depression, as well as in patients with depression and cancer related anxiety have demonstrated immediate and sustained antidepressant and anxiolytic effects. Psilocybin has a favorable safety profile and was well-tolerated in clinical trials. Psilocybin's abuse potential is low and clinical research suggests the potential of psilocybin to produce rapid and lasting antidepressant effects up to 12 months post-treatment. Psilocybin may offer a valuable contribution as an option to the currently available pharmacological and psychotherapeutic agents for patients with major depressive disorders, treatment-resistant depression as well as for patients with depression and comorbid terminal cancer. Future studies are needed to demonstrate these findings and any synergistic interaction between psilocybin and the psychological support offered to patients during sessions.

Unveiling the interoception impairment in various major depressive disorder stages.

BACKGROUND: The intricate pathophysiological mechanisms of major depressive disorder (MDD) necessitate the development of comprehensive early indicators that reflect the complex interplay of emotional, physical, and cognitive factors. Despite its potential to fulfill these criteria, interoception remains underexplored in MDD. This study aimed to evaluate the potential of interoception in transforming MDD's clinical practices by examining interoception deficits across various MDD stages and analyzing their complex associations with the spectrum of depressive symptoms. METHODS: This study included 431 healthy individuals, 206 subclinical depression individuals, and 483 MDD patients. Depressive symptoms and interoception function were assessed using the PHQ-9 and MAIA-2, respectively. RESULTS: Interoception dysfunction occurred in the preclinical phase of MDD and further impaired in the clinical stage. Antidepressant therapies showed limited efficacy in improving interoception and might damage some dimensions. Interoceptive dimensions might predict depressive symptoms, primarily enhancing negative thinking patterns. The predictive model based on interoception was built with random split verification and demonstrated good discrimination and predictive performance in identifying MDD. CONCLUSIONS: Early alterations in the preclinical stage, multivariate associations with depressive symptoms, and good discrimination and predictive performance highlight the importance of interoception in MDD management, pointing to a paradigm shift in diagnostic and therapeutic approaches.

Combination of Transcranial Magnetic Stimulation and Ketamine in Treatment-Resistant Depression: A Systematic Review.

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.

Shared genetic architecture of cortical thickness alterations in major depressive disorder and schizophrenia.

BACKGROUND: Major depressive disorder (MDD) and schizophrenia (SCZ) are heritable brain disorders characterized by alterations in cortical thickness. However, the shared genetic basis for cortical thickness changes in these disorders remains unclear. METHODS: We conducted a systematic literature search on cortical thickness in MDD and SCZ through PubMed and Web of Science. A coordinate-based meta-analysis was performed to identify cortical thickness changes. Additionally, utilizing summary statistics from the largest genome-wide association studies for depression (Ncase = 268,615, Ncontrol = 667,123) and SCZ (Ncase = 53,386, Ncontrol = 77,258), we explored shared genomic loci using conjunctional false discovery rate (conjFDR) analysis. Transcriptome-neuroimaging association analysis was then employed to identify shared genes associated with cortical thickness alterations, and enrichment analysis was finally carried out to elucidate the biological significance of these genes. RESULTS: Our search yielded 34 MDD (Ncase = 1621, Ncontrol = 1507) and 19 SCZ (Ncase = 1170, Ncontrol = 1043) neuroimaging studies for cortical thickness meta-analysis. Specific alterations in the left supplementary motor area were observed in MDD, while SCZ exhibited widespread reductions in various brain regions, particularly in the frontal and temporal areas. The conjFDR approach identified 357 genomic loci jointly associated with MDD and SCZ. Within these loci, 55 genes were found to be associated with cortical thickness alterations in both disorders. Enrichment analysis revealed their involvement in nervous system development, apoptosis, and cell communication. CONCLUSION: This study revealed the shared genetic architecture underlying cortical thickness alterations in MDD and SCZ, providing insights into common neurobiological pathways. The identified genes and pathways may serve as potential transdiagnostic markers, informing precision medicine approaches in psychiatric care.

The adjustment disorder is not a wastebasket diagnosis: a grounded theory study of psychiatrists' and psychologists' clinical reasoning.

Background: the aim of this study is to understand the diagnostic process undertaken by psychiatrists and psychologists regarding adjustment disorder (AD) in their clinical practice and how they differentiate it from major depressive episode (MDE).Methods: A hermeneutic study using grounded theory techniques was carried out. Semi-structured interviews were conducted with twelve psychiatrists and eight psychologists in Colombia, and transcribed verbatim. Initial line-by-line coding was performed, followed by focused and axial coding to construct categories explaining the professionals' reasoning process.Results: The clinical reasoning of professionals regarding AD was understood through four major categories. (1) Difficulty in addressing the experience of stressful events, as there is a risk of pathologizing and medicalizing them. (2) Mental health diagnoses are necessary but not apodictic. (3) The diagnostic category of AD allows for the description of a fluctuating depressive and anxious syndrome occurring in reaction to a stressful event, whose abnormality criteria are based on intersubjective knowledge of the patient's life history and consequential reasoning regarding the need for professional support. (4) The AD label could potentially protect against overdiagnosis of MDE and overuse of antidepressants. Many clinicians in their practice thus subordinate the diagnosis of MDE to ensuring it is not AD, contrary to what is outlined in diagnostic manuals.Conclusion: This study allowed us to understand the clinical reasoning of psychiatrists and psychologists about AD as a diagnosis that inherently indicates the need to work on coping and intervene in the stressor and should be considered as a diagnostic possibility in the same hierarchy as MDE in reactive syndromes, rather than a residual category.

Clinicians use consequential and intersubjective reasoning to diagnose Adjustment Disorder (AD).Systemic pressures lead to overdiagnosis of Major Depressive Episode (MDE) and excessive antidepressant use.AD should be recognized as a valid non-residual diagnostic category.

Mendelian randomization of individual sleep traits associated with major depressive disorder.

BACKGROUND: Observational studies have shown that individual sleep traits habits are potential risk factors for major depression. However, it is not known whether there is a causal relationship between individual sleep traits habits such as continuous sleep duration, short sleep duration, short sleep duration, insomnia, nap during the day, snoring, and major depression. In this study, Mendelian randomization (MR) was used to predict major depressive disorder (MDD) in individuals sleep traits habits. METHODS: Data were obtained from the genome-wide association study (GWAS). Nine MR analysis methods were used: Inverse Variance Weighted (IVW) [fixed effects/multiplicative random effects], simple mode, simple mode, weighted mode, simple median, weighted median, penalised weighted median, and MR-Egger, MR Egger (bootstrap). IVW was used as the main analysis method for the MR analysis of two samples, and the other methods were used as supplements. RESULTS: The results obtained through the IVW method supported a causal relationship between sleep duration and decreased risk of MDD (odds ratio, ORivw: 0.998; 95 % CI: 0.996-0.999, P<0.001). Two-Sample MR, results showed that short sleep duration has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.179; 95 % CI: 1.108-1.255, P<0.001). However, there were no sufficient evidence supported that long sleep duration has a causal effect on the decreased risk of MDD (odds ratio, ORivw: 0.991; 95 % CI: 0.924-1.062, P = 0.793). A significant causal relationship between insomnia and increased risk of MDD was observed (OR: 1.233; 95 % CI: 1.214-1.253, P<0.001). Interestingly, our study also found that daytime napping has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.519; 95 % CI: 1.376-1.678, P<0.001). The present results did not show a significant causal relationship between snoring and the risk of MDD (ORivw: 1.000; 95 % CI: 0.998-1.002, P = 0.906). Obstructive sleep apnea (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) and morning person (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) have no causal effect on the increased risk of MDD. LIMITATIONS: The study could not ascertain whether there were genetic differences among different ethnicities, nations, and regions, as it only included participants of European ancestry. CONCLUSIONS: In summary, our research provides genetic evidence for the relationship between individual sleep traits (short sleep duration, insomnia, daytime napping) and the increased risk of MDD. Interventions targeting lifestyle factors may reduce the risk of MDD.

Helpful or harmful? The effect of a diagnostic label and its later retraction on person impressions.

Diagnostic labels for mental health conditions can inadvertently reinforce harmful stereotypes and exacerbate stigma. If a diagnosis is incorrect and a label is wrongly applied, this may negatively impact person impressions even if the inaccurate label is later corrected. This registered report examined this issue. Participants (N = 560) read a vignette about a hospital patient who was either diagnosed with schizophrenia, diagnosed with major depressive disorder, or not diagnosed with a mental health condition. The diagnostic labels were later retracted strongly, retracted weakly, or not retracted. Participants completed several stigma measures (desire for social distance, perceived dangerousness, and unpredictability), plus several inferential-reasoning measures that tested their reliance on the diagnostic label. As predicted, each mental health diagnosis elicited stigma, and influenced inferential reasoning. This effect was stronger for the schizophrenia diagnosis compared to the major depressive disorder diagnosis. Importantly, the diagnostic label continued to influence person judgments after a clear retraction (strong or weak), highlighting the limitations of corrections in reducing reliance on person-related misinformation and mental health stigma.

Identification of Pyroptosis-Related Molecular Subtypes and Diagnostic Model development in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent psychological disorder associated with inflammation, with complex pathological mechanisms. Pyroptosis has been suggested to contribute to inflammation in central nervous system diseases. Little research, however, has examined what role pyroptosis played in MDD. In the present study, the differential expression pyroptosis-related genes (DE-PRGs) in MDD were identified from the GEO database (GSE98793 and GSE19738). Then, consensus clustering analysis was used to evaluate differences in MDD molecular subtypes characteristics based on PRGs. The characteristic diagnostic biomarkers for MDD were identified by Weighted Correlation Network Analysis (WGCNA) and multiple machine learning algorithms. Three intersection genes (GZMA, AKR1C3, and CD52) were obtained, which are expected to become potential biomarkers for MDD with excellent reliability and accuracy. Subsequently, the immune infiltration characteristics result indicated that the development of MDD is mediated by immune-related function, where three DE-PRGs were strongly related to the immune infiltration landscape of MDD. The biological experiments in vitro further proved that three unique PRGs are emerging as important players in MDD diagnosis. Our research aimed to provide novel ideas and biomarkers targeting MDD.

Is Nasal Dysbiosis a Required Component for Neuroinflammation in Major Depressive Disorder?

Human microbiota is known to influence immune and cerebral responses by direct and/or indirect mechanisms, including hypothalamic-pituitary-adrenal axis signaling, activation of neural afferent circuits to the brain, and by altering the peripheral immune responses (cellular and humoral immune function, circulatory inflammatory cells, and the production of several inflammatory mediators, such as cytokines, chemokines, and reactive oxygen species). The inflammatory responses in the nasal mucosa (rhinitis) or paranasal sinuses (chronic rhinosinusitis) are dual conditions related with a greater risk for developing depression. In the nasal cavity, anatomic components of the olfactive function are in direct contact with the CNS through the olfactory receptors, neurons, and axons that end in the olfactory bulb and the entorhinal cortex. Local microbiome alterations (dysbiosis) are linked to transepithelial translocation of microorganisms and their metabolites, which disrupts the epithelial barrier and favors vascular permeability, increasing the levels of several inflammatory molecules (both cytokines and non-cytokine mediators: extracellular vesicles (exosomes) and neuropeptides), triggering local inflammation (rhinitis) and the spread of these components into the central nervous system (neuroinflammation). In this review, we discuss the role of microbiota-related immunity in conditions affecting the nasal mucosa (chronic rhinosinusitis and allergic rhinitis) and their relevance in major depressive disorders, focusing on the few mechanisms known to be involved and providing some hypothetical proposals on the pathophysiology of depression.