Major Depressive Disorder Research Articles

Optimizing anesthesia depth to enhance seizure quality during electroconvulsive therapy in major depressive disorder

This editorial evaluated the findings of a comprehensive study focused on the effects of anesthesia depth on seizure parameters during electroconvulsive therapy (ECT) in patients with major depressive disorder. The study utilized quantitative consciousness and quantitative nociceptive indices for monitoring sedation, hypnosis, and nociceptive responses. The analysis included 193 ECT sessions across 24 patients, revealing significant impacts of anesthesia depth on electroencephalography (EEG) seizure parameters. Key findings include that lighter anesthesia resulted in longer EEG seizure duration and higher post-ictal suppression index, without increasing complications. These insights emphasize the importance of optimal anesthesia management to improve therapeutic outcomes in ECT.

Correlation between self-efficacy, parental parenting patterns, and severe depression in adolescents

BACKGROUND Adolescence is a critical period marked by significant psychological changes. This study explores how self-efficacy and parental parenting styles may influence the risk of severe depression among teens. The hypothesis is that higher self-efficacy and authoritative parenting patterns will be negatively correlated with severe depression in adolescents. AIM To investigate the correlation between self-efficacy, parenting patterns and major depression in adolescents, and to provide guidance for mental intervention. METHODS Using a cross-sectional survey design, the data were collected through a questionnaire survey. Patients with major depression and healthy adolescents in the hospital control group were selected as the study objects. The General Self-Efficacy Scale, the Parenting Style Evaluation Scale, and the Beck Depression Inventory were used as research instruments. Data input and statistical analysis were performed, including descriptive statistics, correlation analysis, through SPSS software. RESULTS The study found that depressed patients had significantly lower self-efficacy than healthy controls, and parenting style was significantly associated with depressive symptoms in terms of emotional warmth and understanding, punishment severity, and denial. Specifically, parental emotional warmth and understanding were significantly negatively associated with depressive symptoms, while parental punishment severity and denial were significantly positively associated with depressive symptoms. Self-efficacy showed a significant negative correlation with depressive symptoms, indicating that higher self-efficacy had lower depressive symptoms. CONCLUSION Adolescent major depressive disorder patient was significantly associated with their parenting style and self-efficacy. Higher self-efficacy is associated with decreased depressive symptoms, so improving adolescent self-efficacy and improving parenting style are important.

Agomelatine bears promising potential in treating bipolar depression- a systematic review.

The controversy of antidepressant use in bipolar depression remains controversial. Agomelatine (AGO) is an effective antidepressant in major depressive disorder (MDD), but its application in bipolar depression was little discussed. We aimed to provide a comprehensive systematic review of clinical evidence from studies examining the efficacy and safety of AGO for bipolar depression. We conducted a systematic review about AGO trials for the treatment of bipolar patients. We searched PubMed, MEDLINE, Embase, and Cochrane for relevant studies published since each database's inception. We synthesised evidence regarding efficacy (mood and rhythm) and tolerability across studies. We identified 6 studies including 272 participants (44% female). All studies used 25-50 mg AGO per day for treatment combined or not combined with mood stabilisers (MS). Across all 6 studies, there were improvements in depression evaluated by depression rating scores and response rate over time. The response rates varied from 43% to 91% within 6-12 weeks. Although AGO was found of better efficacy in bipolar depression compared to recurrent depression, its efficacy remains controversial. Most studies have shown AGO to be effective after just about a week. AGO was reasonably well tolerated both in acute and extension period, without obvious risk in inducing mood switching. AGO is promising in treating bipolar depression with significant efficacy and well tolerability. However, more strictly designed and large-sample trials are needed in further research with homogeneity within intervention and treatment groups.

Effects of childhood trauma on sustained attention in major depressive disorder: the mediating role of brain activity and functional connectivity

BackgroundSustained attention deficits were reported more significant in patients with major depressive disorder (MDD) than in healthy controls (HCs), and are pivotal in both the development and aggravation of depression. Childhood trauma is also common in MDD and the exposure to childhood trauma may impede sustained attention and increase the treatment resistance in MDD. However, the underlying neuro-mechanisms link the childhood trauma to sustained attention deficits in MDD remain unclear.MethodsWe collected resting-state functional magnetic resonance imaging data, and measured childhood trauma severity using the Childhood Trauma Questionnaire and sustained attention using the Continuous Performance Test, Identical Pairs version. After excluding subjects with significant head movement, 45 MDDs and 54 HCs were included in the analysis. We compared fractional amplitude of low-frequency fluctuation (fALFF) between the groups, conducted whole-brain correlation analysis between the fALFF and sustained attention in the MDD group, and defined significant regions as the regions of interest for the seed-to-whole brain functional connectivity (FC) analysis. We further performed mediation analyses to investigate the relationships among the childhood trauma, fALFF and FC values, and the level of sustained attention in the MDD group.ResultsCompared with HCs, MDDs exhibited higher fALFF in the right middle frontal gyrus and left inferior frontal gyrus, and lower fALFF in the bilateral insular cortex, left medial orbital superior frontal gyrus and left angular gyrus (ANG.L). Whole-brain correlation analysis showed that impaired sustained attention was associated with increased fALFF in the left postcentral gyrus (PoCG.L), and FC of PoCG.L-left precentral gyrus (PreCG.L) and ANG.L-right superior temporal gyrus (STG.R) in the MDD group. Furthermore, mediation analyses showed that the fALFF in PoCG.L, and FC of PoCG.L-PreCG.L and ANG.L-STG.R mediated the relationship between the childhood trauma and sustained attention in the MDD group.ConclusionThe fALFF in PoCG.L, and FC of PoCG.L-PreCG.L and ANG.L-STG.R might be potential neural substrate in the association between the childhood trauma and poor sustained attention in the MDDs, and might serve as potential intervention targets for the treatment of sustained attention deficits in MDDs with childhood trauma history.

Using hierarchical drift diffusion models to elucidate computational mechanisms of reduced reward sensitivity in adolescent major depressive disorder

BackgroundAnhedonia—a core symptom of major depressive disorder (MDD)—is closely related to diminished reward sensitivity. Nonetheless, the psychopathological and computational mechanism underlying anhedonia in young patients with MDD remains unclear. Therefore, this study aims to investigate reward sensitivity in adolescents and young adults with MDD using computational modelling.MethodsOverall, 70 patients with MDD and 54 age- and sex-matched healthy controls (HC) completed a probabilistic reward task (PRT) to assess their general behavioral inclination towards more frequently reinforced stimuli (i.e., “response bias”). Bayesian hierarchical drift diffusion modeling (HDDM) was employed to determine changes in reward sensitivity and computational process during decision-making.ResultsAdolescents with depression showed a trend toward reduced response bias compared to those in HC. HDDM analysis revealed wider decision thresholds in both adolescents and young adults with MDD group. Adolescents with MDD exhibited significantly lower drift rates and reduced starting point bias compared to those in HC. Higher anhedonia levels were linked to lower drift rates and wider decision thresholds. Additionally, increased discriminability correlated with higher drift rates, while higher response bias was linked to larger starting points.ConclusionsOur findings suggest that reduced reward sensitivity and slower evidence accumulation during reward learning may serve as potential indicators of anhedonia in adolescents with MDD. These findings provided crucial insights into the dysregulated positive affect model, underscoring a dysfunctional reward system as a key factor in anhedonia developmental psychopathology in depression.

The effect of depression on non-suicidal self-injury and psychological status in adolescents with unipolar and bipolar disorders

ObjectiveTo investigate the effects of depression on non-suicidal self-injury (NSSI) and related psychological conditions in adolescents with unipolar disorder (UD) and bipolar disorder (BD), and to provide a basis for accurate prevention and intervention of NSSI behaviors in adolescents.MethodsThis cross-sectional study collected data from adolescents aged 12–18 years with depressive episodes who exhibited NSSI behaviors and attended the psychiatric outpatient clinic of Huangshi City Psychiatric Specialized Hospital from 2018 to 2023. Depressive episodes were clinically diagnosed by two psychiatrists according to the ICD-10.ResultsIn terms of NSSI behavioral patterns and severity, adolescents with UD displayed more frequent behaviour of intentionally burning themselves with cigarettes and had more instances of self-inflicted suicidal thoughts that were not carried out compared to those with BD, and the differences between the two groups were statistically significant (P < 0.05). For psychological status, Nurses′ Global Assessment of Suicide Risk (NGASR) scores were significantly higher in adolescents with BD than in those with UD (P < 0.05). There was a significant negative correlation between anxiety scores and the frequency of NSSI in adolescents with BD (P < 0.05); that is, the more anxious the adolescents with BD, the lower the frequency of NSSI. The NGASR scores of adolescents with UD and BD were significantly and positively correlated with the frequency of NSSI occurrences (P < 0.05); higher NGASR scores of adolescents with UD and BD corresponded with higher frequencies of NSSI.ConclusionThe differences in NSSI behaviors between adolescents with UD and those with BD were statistically significant in terms of self-injury method and severity. Adolescents with UD experienced more severe consequences related to NSSI behaviors. Regarding psychological conditions, adolescents with BD are at a higher risk of suicide. An inverse relationship was observed between anxiety severity and the frequency of NSSI in adolescents with BD; severe anxiety was associated with lower NSSI frequency. Additionally, higher suicide risk was associated with a higher frequency of NSSI in adolescent patients with either UD or BD. Therefore, different prevention and intervention measures are needed to address NSSI behaviors in adolescents with UD and BD.

Associations between internet addiction and suicidal ideation in depressed adolescents: the mediating effect of insomnia as well as sex differences

BackgroundInsomnia may mediate the association between internet addiction (IA) and suicidal ideation (SI). However, such association has not been thoroughly investigated in adolescents with major depressive disorder (MDD). Thus, our study aimed to explore whether insomnia significantly affects the association between IA and SI in adolescents with MDD, as well as any sex differences.MethodsFrom January 2021 to September 2023, this cross-sectional study included 502 adolescents with MDD and 123 healthy controls (HCs). The Clinical Global Impression-Severity (CGI-S), the Internet Addiction Test (IAT), the Insomnia Severity Index Scale (ISI) and the Positive and Negative Suicidal Ideation Scale (PANSI) were used to assess subjects’ severity of depression, IA, insomnia and SI. And we employed the PROCESS macro program to examine the mediating role of insomnia between IA and SI.ResultsCompared to HCs, adolescents with MDD had significantly higher levels of SI and their prevalence of IA and insomnia were 50.0% and 35.7%. In patients, PANSI scores correlated negatively with age and age of onset, and positively with disease duration as well as the scores of the CGI-S, IAT, and ISI (all p < 0.01). Moreover, above-mentioned correlations were more significant in girls. Mediation analyses showed that insomnia mediated the effect of IA on SI, and the total, direct, and indirect effects were 0.197 (95% CI: 0.132—0.262), 0.157 (95% CI: 0.096—0.218) and 0.040 (95% CI: 0.014—0.068), respectively. In female patients, the total, direct, and indirect effects were 0.224 (95% CI: 0.151—0.296), 0.191 (95% CI: 0.124—0.257) and 0.033 (95% CI: 0.002—0.068), respectively. In male patients, insomnia acted as a fully mediated effect between IA and SI, with an effect value of 0.045 (95% CI: 0.008—0.093).ConclusionDepressed adolescents have higher suicide risk, and SI is significantly associated with IA and insomnia, especially in girls. Moreover, insomnia may mediate the association between IA and SI. However, given the small sample size of this study and the limitations of assessment tools used, the results need to be viewed with caution. Regardless, clinical interventions should be strengthened for IA and insomnia in adolescents with MDD to reduce suicide risk.

Unraveling the causal relationship and potential mechanisms between osteoarthritis and breast cancer: insights from mendelian randomization and bioinformatics analysis

ObjectiveTo investigate the effect of osteoarthritis (OA) on the development of breast cancer (BC), and reveal the potential mechanisms underlying the association between them.MethodsA two-step, multivariable Mendelian Randomization (MR) analysis was performed, using statistics from genome-wide association studies (GWAS), to determine the effect of OA on BC and explore the role of major depressive disorder (MDD) in mediating it. Furthermore, transcriptomic analysis based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to establish a prognostic model and explore the underlying mechanisms. Additionally, BC cells and nude mice were used to verify the role of RTN4 in BC.ResultsThe two-sample MR analysis implied a causal relationship between OA and BC at the genetic level, and the mediating MR analysis identified that MDD may play a potential role in mediating it, accounting for approximately 12.20%. Then, we constructed a prognostic model (OA-score) with six genes screened out from datasets and selected RTN4 as the representative gene for validation study. It was demonstrated that high OA-score was an independent risk factor for breast cancer, and patients with low OA-score were more likely to have better OS, higher infiltration level of DC and CD 4 + T cells, and higher expression of some immune checkpoints. Moreover, the knockdown of RTN4 inhibited breast cancer cell proliferation, migration and invasion.ConclusionOur study identified the causal influence of OA on BC mediated by MDD at the genetic level. OA-Score may potentially serve as a new prognostic biomarker for OA related BC patients.

A mobile-based randomized controlled trial on the feasibility and effectiveness of screening for major depressive disorder: study protocol

BackgroundMobile-based screening interventions to detect and treat Major Depressive Disorder (MDD) at an early stage might be a promising approach for reducing its societal burden. In the present study, we will evaluate the feasibility and effectiveness of screening for MDD using a mobile-based screening protocol.MethodsThis study will be a three-arm, parallel randomized control trial (RCT) performed in a multi-ethnic population within the municipality of Rotterdam (the Netherlands). The trial includes two intervention groups that will be screened 4-weekly for MDD for 12 months using the Patient Health Questionnaire (PHQ-9) and a control group who does not receive mobile-based screening for MDD. Participants in the one-test intervention arm will be referred for further diagnosis and treatment, if necessary, after a single positive test score for moderate-severe major depression symptoms (PHQ-9 > 10). Participants in the multiple-test intervention arm will only be referred after three consecutive positive test scores. 1786 eligible participants will be included in the RCT, with 446 and 447 in the one-test and multiple-test referral arms, respectively, and 893 in the control arm. Primary outcome is participants’ QoL after 12 months (EQ-5D-5L). Secondary outcomes include participants’ QoL after 24 months (EQ-5D-5L), evaluating the occurrence and severity of MDD symptoms (PHQ-9), intervention engagement, and identifying public mental health differences based on sociodemographic characteristics, including age, gender, ethnicity, financial situation, educational background, and living area. Long-term results of the RCT will be incorporated into a microsimulation model to determine the long-term benefits, harms, and costs of MDD screening.DiscussionThe information gained from examining the feasibility and (cost-) effectiveness of mobile-based screening for MDD could be of guidance for mental health policy implementations and support the introduction of mobile-based screening for MDD in the Netherlands and/or other nations.Trial registrationClinicalTrials.gov: NL84280.078.23, NCT05989412, August 8, 2024.

Treatment with combined exercise in patients with resistant major depression (TRACE-RMD): study protocol for a randomised controlled trial

BackgroundAround 40% of people with major depressive disorder (MDD) experience moderate remission, with the remainder meeting the criteria for resistant major depression (RMD). It has been shown that exercise has a low-to-moderate effect on MDD, but there is a lack of evidence on exercise interventions in RMD patients. The primary purpose of the proposed study will be to investigate the effect of a 12-week supervised combined exercise program on depressive symptoms in people with RMD compared to a treatment-as-usual (TAU) group.MethodThis randomised, single-blind, controlled experimental trial will include 70 adults (≥ 18 years old) with RMD. Participants randomised to an exercise intervention, or a TAU group will be assessed at baseline and after a three-month intervention period. The primary variable will be participants’ depressive symptoms measured with the Montgomery-Asberg Depression Rating Scale. Secondary outcome variables will include cardiorespiratory fitness (peak oxygen uptake through peak cardiopulmonary exercise test), body composition (bioimpedance and anthropometric variables), physical activity level (the International Physical Activity Questionnaire), health-related quality of life (the Short Form-36 Health Survey), functional outcome (the Sheehan Disability Scale and Quality of Life in Depression Scale), overall disease severity (the Clinical Global Impression Scale-Severity of Illness), and biochemical variables (a fasting blood sample).DiscussionThis study will try to answer whether a supervised co-adjuvant combined (aerobic and resistance training) exercise program will help the prognosis of this population with RMD.Trial registrationClinicalTrials.gov NCT05136027. Last public release on 12/13/2023.

Altered dynamic functional connectivity in antagonistic state in first-episode, drug-naïve patients with major depressive disorder

ObjectiveMajor depressive disorder (MDD) is known to be characterized by disrupted brain functional network connectivity (FNC) patterns, while the dynamic change mode of different functional networks is unclear. This study aimed to characterize specific dynamic alterations pattern on intrinsic FNC in MDD by combining static FNC (sFNC) and dynamic FNC (dFNC).MethodsA total of 48 first-episode drug-naïve MDD and 48 matched healthy controls (HCs) were included in this study. The sFNC and dFNC were analyzed using complete time-series and sliding window approach, respectively. Both sFNC and dFNC differences between groups were analyzed and associations between disease severity and aberrant FNC were explored.ResultsMDD patients exhibited lower sFNC within and between sensory and motor networks than HC. Four dFNC states were identified, including a globally-weakly-connected state, a cognitive-control-dominated state, a globally-positively-connected state, and an antagonistic state. The antagonistic state was marked by strong positive connections within the sensorimotor domain and their anti-correlations with the executive-motor control domain. Notably, MDD patients exhibited significantly longer dwell time in the globally-weakly-connected state, at the cost of significantly shorter dwell time in the antagonistic state. Further, only the mean dwell time of this antagonistic state was significantly anticorrelated to disease severity measures.ConclusionsOur study highlights the altered dynamics of the antagonistic state as a fundamental aspect of disrupted FNC in early MDD.

Newly estimated disability weights for 196 health states in Hubei Province, China

BackgroundThe disability weight (DW) reflects the severity of non-fatal outcomes and is an important parameter in calculating the burden of disease. However, the universality of the global, national, or subnational DWs remains controversial. This study aims to measure DWs specific to Hubei Province of China using non-parametric regression to anchor the DWs.MethodsPaired comparison (PC) data collected from a web-based survey in Hubei Province targeting the general population were used to estimate the DWs of 196 health states. Specifically, PC data from 33,925 respondents were analyzed by probit regression analysis, and the results were then anchored to 0–1 scale using non-parametric regression based on the DWs from Global Burden of Disease (GBD) 2013. The absolute DW values and rankings were compared to those in the Chinese disability weight measurement study, GBD 2013, and Japan.ResultsThe DWs for 196 health states ranged from 0.003 for mild distance vision impairment to 0.663 for severe heroin and opioid dependence in Hubei Province, China. Quite a lot mental disorders, such as moderate/severe episode of major depressive disorder, were considered more severe than the terminal phase with/without medication among Hubei residents. DW rankings of the health states are relatively stable in Hubei Province irrespective of the anchoring method used. A very small proportion (4 of 196, 2%) of DW rankings changed by 10 or more positions in China when compared with our results, but approximately 61% in GBD 2013 and 59% in Japan. Among the top 25 health states in this study, 9 of 11 health states categorized as mental, behavioral, and substance use disorders resulted in a lower ranking in GBD 2013, and all 6 states in Japan also showed a lower ranking, whereas China shared a similar ranking.ConclusionsThe burden of mental disorders among Hubei residents, especially moderate or severe major depressive disorder, deserves further attention. When using different anchoring methods, DW rankings were maintained relatively stable rather than the absolute values in Hubei. Substantial differences of DW rankings between our results and that in China, GBD 2013, and Japan draw attention to the need for deriving local disability for disease burden calculation.

Antidepressant response time across intermittent theta burst stimulation regimens and efficacy indicators in adolescents depression: a secondary analysis from a randomized controlled trial

BackgroundAccelerated intermittent theta burst stimulation (aiTBS), which involves the administration of multiple daily sessions of iTBS, represents a novel regimen of repetitive transcranial magnetic stimulation. Studies have suggested that aiTBS may facilitate a fast response among patients with major depressive disorders. However, whether aiTBS can accelerate antidepressant response in adolescents suffering from depression is still unclear. Additionally, the potential indicators associated with antidepressant response in this population are still understudied.MethodsNinety adolescents with depression were recruited and randomly assigned to aiTBS (two 600-pulse sessions of iTBS spaced for 10 min, N = 31), iTBS (one 600-pulse session, N = 29), or sham iTBS (N = 30) for two treatment weeks. Kaplan–Meier analysis was used to estimate the mean time to antidepressant response among the three groups. The analysis of covariance and the multiple logistic regression were applied to identify potential indicators associated with treatment response.ResultsThe mean time to antidepressant response was 7.45 weeks (95% CI: 6.19–8.72) in the aiTBS group, 5.62 weeks (95% CI: 4.09–7.16) in the iTBS group, and 5.07 weeks (95% CI: 3.56–6.58) in the sham group, respectively. The log rank test revealed no significant difference in the mean time to antidepressant response among the three groups (χ2 = 4.156, p = 0.125). For the antidepressant response, there were also no significant interactions between iTBS treatment regimens and the baseline characteristics. Notably, participants with higher motor threshold and worse global function at baseline were likely to be associated with early response and final response, respectively, while those who experiencing child-parent separation were associated with both early and final response. In addition, younger participants were more likely to experience recurrence during follow-up.ConclusionsaiTBS did not demonstrate an advantage in terms of a fast antidepressant response. However, some pretreatment characteristics might serve as indicators of antidepressant response. This relatively simple application based on pretreatment characteristics seems to be a cost-effective method to identify adolescents who are more likely to develop an early antidepressant response and sustain it.Trial registrationThis is a secondary analysis of a primary RCT, which was officially registered in the Chinese Clinical Trial Registry at 19/1/2021 with the number of ChiCTR2100042346. https://www.chictr.org.cn/bin/project/edit?pid=66118.

Psilocybin increases emotional empathy in patients with major depression.

Empathy plays a crucial role in interpersonal relationships and mental health. It is decreased in a variety of psychiatric disorders including major depression. Psilocybin, a promising candidate for treating depression, has been shown to acutely increase emotional empathy in healthy volunteers. However, no study has investigated this effect and its relevance for symptom improvement in a clinical population. This study examines the enduring effects of psilocybin-assisted therapy on empathy in depressed patients using a randomized, placebo-controlled design. Fifty-one depressed patients were randomly assigned to receive a single dose of psilocybin (0215 mg/kg body weight) or a placebo embedded in a 4-week psychological support intervention. Empathy was measured using the Multifaceted Empathy Test at baseline and 2 days, 1 week, and 2 weeks after substance administration. Changes in empathy were compared between treatment conditions. Patients who received psilocybin showed significant improvements in explicit emotional empathy driven by an increase in empathy towards positive stimuli compared to the placebo group for at least two weeks. This study highlights the potential of psychedelics to enhance social cognition in individuals living with depression and contributes to a better understanding of the psychological mechanisms of action of psychedelics. Further studies are necessary to investigate the interaction between social cognition and clinical efficacy.The trial is registered on clinicaltrials.gov (Identifier: NCT03715127) and KOFAM (Identifier: SNCTP000003139).

Mental Illness Stigma in Black, Latina/o, and Asian Americans.

Mental illness stigma has significant psychiatric consequences and can impede mental health treatment seeking, especially among racial minority groups; who are understudied in stigma research and experience striking treatment disparities. Guided by a novel empirical model of racial minority stigma and treatment seeking, this study investigated stigma and its effects on treatment seeking in Black, Latina/o, and Asian American adults. Data were collected via national panel survey from 613 Black, Latina/o, and Asian American adults. Perceptions of mental illness including seriousness, treatability, causal attributions, desired social distancing, and perceived dangerousness were assessed. Data were analyzed and compared with a nationally representative sample of the U.S. public from the 2018 General Social Survey. Minority participants exhibited stronger mental illness stigma than the U.S. public, with Black, Latina/o, and Asian American participants largely perceiving mental illness as less serious, less treatable, and desiring greater social distance from individuals with major depression, who were perceived as potentially dangerous. Notably, different stigma components significantly associated with willingness to seek treatment differently across Black, Latina/o, and Asian American participants. Overall, study findings indicate that mental illness stigma is strong and associates with treatment seeking in Black, Latina/o, and Asian Americans, suggesting a need to develop culturally tailored interventions to reduce stigma and associated treatment utilization disparities in these underserved minority groups.

Exploring autism spectrum disorder and co-occurring trait associations to elucidate multivariate genetic mechanisms and insights

BackgroundAutism spectrum disorder (ASD) is a partially heritable neurodevelopmental trait, and people with ASD may also have other co-occurring trait such as ADHD, anxiety disorders, depression, mental health issues, learning difficulty, physical health traits and communication challenges. The concomitant development of ASD and other neurological traits is assumed to result from a complex interplay between genetics and the environment. However, only a limited number of studies have performed multivariate genome-wide association studies (GWAS) for ASD.MethodsWe conducted to-date the largest multivariate GWAS on ASD and 8 ASD co-occurring traits (ADHD, ADHD childhood, anxiety stress (ASDR), bipolar (BIP), disruptive behaviour (DBD), educational attainment (EA), major depression, and schizophrenia (SCZ)) using summary statistics from leading studies. Multivariate associations and central traits were further identified. Subsequently, colocalization and Mendelian randomization (MR) analysis were performed on the associations identified with the central traits containing ASD. To further validate our findings, pathway and quantified trait loci (QTL) resources as well as independent datasets consisting of 112 (45 probands) whole genome sequence data from the GEMMA project were utilized.ResultsMultivariate GWAS resulted in 637 significant associations (p < 5e-8), among which 322 are reported for the first time for any trait. 37 SNPs were identified to contain ASD and one or more traits in their central trait set, including variants mapped to known SFARI ASD genes MAPT, CADPS and NEGR1 as well as novel ASD genes KANSL1, NSF and NTM, associated with immune response, synaptic transmission, and neurite growth respectively. Mendelian randomization analyses found that genetic liability for ADHD childhood, ASRD and DBT has causal effects on the risk of ASD while genetic liability for ASD has causal effects on the risk of ADHD, ADHD childhood, BIP, WA, MDD and SCZ. Frequency differences of SNPs found in NTM and CADPS genes, respectively associated with neurite growth and neural/endocrine calcium regulation, were found between GEMMA ASD probands and controls. Pathway, QTL and cell type enrichment implicated microbiome, enteric inflammation, and central nervous system enrichments.ConclusionsOur study, combining multivariate GWAS with systematic decomposition, identified novel genetic associations related to ASD and ASD co-occurring driver traits. Statistical tests were applied to discern evidence for shared and interpretable liability between ASD and co-occurring traits. These findings expand upon the current understanding of the complex genetics regulating ASD and reveal insights of neuronal brain disruptions potentially driving development and manifestation.

Beyond Mono-Method Symptom Assessment: Multimethod Extension of the Trilevel Model of Anxiety and Depression

The wide array of symptoms of and high comorbidity rates between unipolar depressive and anxiety-related disorders have raised questions about the relations among their symptoms. Factor analysis examines these relations, yet factor-analytic symptom-measurement models have relied on a single method of measurement and do not always replicate. We conceptually replicate and extend the trilevel model of anxiety and depression symptoms to encompass interviewer-rated symptoms. In the trilevel model, symptom-specific items load on three levels of factors: a narrow (or disorder-specific) factor, an intermediate-breadth factor, and a general-distress factor. The trilevel model fit well in this sample and fit better than comparison models that eliminated one of the three levels. Extension analysis successfully integrated interviewer-rating variables into the trilevel model—particularly for the broad and narrow levels. These results provide some support for the trilevel model and the use of interviewer ratings of symptoms. Research and treatment implications are discussed.

The role of gut microbiota and metabolomic pathways in modulating the efficacy of SSRIs for major depressive disorder

This study aims to explore the mechanism by which gut microbiota influences the antidepressant effects of serotonin reuptake inhibitors (SSRIs) through metabolic pathways. A total of 126 patients were analyzed for their gut microbiota and metabolomics. Patients received SSRI treatment and were categorized into responder and non-responder groups based on changes in their Hamilton Depression Rating Scale (HAMD-17) scores before and after treatment. The association between gut microbiota composition and the efficacy of SSRIs was investigated through 16S rRNA gene sequencing and metabolomic analysis, and a predictive model was developed. As a result, the study found significant differences in gut microbiota composition between the responder and resistant groups. Specific taxa, such as Ruminococcus, Bifidobacterium, and Faecalibacterium, were more abundant in the responder group. Functional analysis revealed upregulation of acetate degradation and neurotransmitter synthesis pathways in the responder group. The machine learning model indicated that gut microbiota and metabolites are potential biomarkers for predicting SSRIs efficacy. In conclusion, gut microbiota influences the antidepressant effects of SSRIs through metabolic pathways. The diversity and function of gut microbiota can serve as biomarkers for predicting the treatment response, providing new insights for personalized treatment.

Features of mental state and reproductive function in dynamics inmentally ill women with infertility

Women suffering from a mental disorder are faced with the problem of pregnancy and the realisation of their reproductive rights throughout their lives. The presence of a mental disorder largely determines the onset, course and outcome of pregnancy. A deterioration in mental health is often accompanied by an impairment of menstrual and reproductive function, and an improvement contributes to their recovery.Objective: to analyse individual indicators of reproductive function in women with various mental disorders and infertility in dynamics according to the follow-up data.Material and methods. The study included 120 women with various mental disorders and infertility, who were observed for 2 years by a psychiatrist and a gynaecologist on the background of treatment of the existing disorders.Results. In 70% of cases, mentally ill women have primary infertility, with idiopathic infertility predominating (63.3%), especially in the context of secondary infertility (77.8%; p&lt;0.05). Treatment of infertility by gynaecologists and mental disorders by psychiatrists leads to the normalization of the menstrual cycle and the onset of pregnancy. Pregnancy is usually accompanied by obstetric and somatic complications (fetal growth retardation and miscarriage, placental disorders, hypertension, oedema, lipid metabolism disorders, gestational diabetes mellitus). Reproductive function is impaired mostly in patients with schizophrenia and affective disorders, they account for 80.8% of observed infertility. Fertility is lowest in patients with paranoid schizophrenia: pregnancy occurred in 12.9% of patients, none of them gave birth. In schizoaffective disorder, 43.75% of women became pregnant, but only 20% gave birth. In bipolar affective disorder (BAD) type I, pregnancy occurred in 87.5% of patients (of which 57.1% resulted in a childbirth), in bipolar disorder type II – in 43.75% (of which 42.8% resulted in a childbirth), and in recurrent depressive disorder – in 60% (of which 50% resulted in a childbirth). In these disorders, the duration of infertility correlates with the duration of the disease (p&lt;0.05). In neurotic disorders, fertility suffers to a lesser extent: pregnancy with recovery or significant improvement of the mental condition occurred in 75–100% of cases, but only 66.7% of cases resulted in a child birth. Childbirth was mainly performed by caesarean section.Conclusion. Reproductive function in mentally ill women depends largely on the type of mental disorder, the characteristics of its course, the efficacy of psychopharmacotherapy, the quality of remission and the degree of social and family adaptation, which must be taken into account in the diagnosis and treatment of infertility.

Combining pleasant Olfactory and BRAin stimulations in treatment-resistant depression (COBRA): study protocol for a randomized controlled trial

BackgroundAnhedonia, including social, physical, and less-known, olfactory, stands as a core symptom of major depressive disorder (MDD). At the neurobiological level, anhedonia has been associated with abnormal activity within the reward system, suggesting a key role for dopamine. Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as an innovative treatment for alleviating depressive symptoms. Stimulation of the dorsolateral prefrontal cortex (DLPFC) has been shown to both improve anhedonia and induce dopamine release. Moreover, research suggests that the efficacy of rTMS is improved when applied to an activated brain network rather than at rest. Our goal is to induce a dual activation of the reward system using a combined rTMS protocol and an intervention based on pleasant odorant exposure known to stimulate this system.MethodsIn this randomized controlled trial, we propose to combine rTMS targeting the left DLPFC with pleasant odorant stimulation to alleviate depressive symptoms. A total of 80 patients with treatment-resistant MDD will be randomly assigned to two groups and will receive 50 sessions of either: 1- rTMS and hedonic olfactory stimulations, or 2- rTMS alone. We will conduct pre- and post-assessments measuring depression severity, physical, social, and olfactory anhedonia, as well as the connectivity and activity of brain regions involved in the pathophysiology of depression and the reward circuitry.DiscussionThis study may strengthen the development of more effective rTMS interventions and pave the way for the establishment of rTMS combined with olfactory training as a safe, effective, and easily accessible treatment for MDD patients. In addition, this study will contribute to a better understanding of the mechanisms and physiopathology of MDD.Trial registration number#NCT05661383.