It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.

To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.

Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.

IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).

Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.

Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.

The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.

This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.

While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches.

Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation.

A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3–2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83–7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2–10.5%; RR: 1.56, 95% CI: 1.38–1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2–11.3%; RR: 1.60, 95% CI: 1.42–1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses.

Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.

Self-compassion (SC) describes an emotionally positive attitude extended toward ourselves when we suffer, consisting of three main components; self-kindness, common humanity, and mindfulness (Germer & Neff, 2013). SC entails being warm and understanding towards ourselves when encountering pain or personal shortcomings, rather than ignoring them or flagellating ourselves with self-criticism. SC also involves recognizing that suffering and failure are part of the shared human experience rather than isolating. In addition, SC requires taking a mindful approach to one’s feelings and thoughts, without judgment of them.

Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing depression and anxiety in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied.

Magnetic resonance imaging data were acquired from 71 healthy participants with measured levels of SC and its six subscales. Mirroring network as WM regions of interest were analyzed using tract-based spatial statistics (TBSS). After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed.

We found that self-compassion scale (SCS) total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores of SCS were also negatively correlated with FA values of the same regions. The FA values of SLF related to SC were found to be negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy.

Our findings suggest that levels of SC and its self-kindness and mindfulness components may be negatively associated with DMN-related WM microstructures in healthy individuals. These less WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies.

None Declared

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD).

To investigate the genomic architecture of ASD in terms of non-coding de novo mutations and 3-dimensional chromatin interactions

We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions.

Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development.

Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

None Declared

Lamina-specific alterations of inhibitory circuitries have been considered the crucial pathogenesis of perceptual, cognitive and behavioral symptoms presented in schizophrenia and mood disorders. Especially, with emerging evidences indicating the close lamina-specific relationship between synaptic defects and γ-Aminobutyric acid (GABA)-related gene dysfunctions, it has been suggested the mRNA dysregulations of Tyrosine kinase B (TrkB) and Glutamate decarboxylase 67 (GAD67) could particularly be implicated in middle and deep layers of neocortex of patients with major psychiatric disorders.

Giving inquiries of whether defects of these mRNA levels in Orbitofrontal cortex (OFC) would be involved as lamina-specific patterns in individuals with schizophrenia and mood disorders.

We examined mRNA levels of BDNF, TrkB and GAD67 in each OFC layer I through VI. We analyzed data from postmortem brain tissue of the Stanley Neuropathology Consortium Integrative Database (SNCID). SNCID consists of 15 subjects in each of four groups (schizophrenia, bipolar disorder, major depression without psychotic features, and unaffected controls). All groups were matched for age, sex, race, brain pH and post-mortem interval.

We found TrkB mRNA levels to be significantly reduced in layer VI in both groups with schizophrenia (25.8%) and bipolar disorder (35.7%) compared with controls. GAD67 mRNA levels were also significantly reduced in layer III and IV in patients with schizophrenia (23.4% and 22.7%, respectively) and bipolar disorder (31.2% and 24.9%, respectively) compared with controls. Individuals with major depression showed only trends toward decreased mRNA levels of GAD67 in layer III and IV and of TrkB in layer VI compared with controls. TrkB mRNA levels in layer VI were significantly correlated with GAD67 mRNA levels in layer III (ρ=0.581, p=0.037) and IV (ρ=0.857, p<0.001) in subjects with bipolar disorder, but not in those with schizophrenia. When analyzed with partial correlation controlling the effects of pH and PMI, significance of correlation remained only between GAD67 mRNA in layer IV and TrkB mRNA in layer VI in individuals with bipolar disorder (ρ=0.768, p=0.006).

The resulting lamina-specific decreases in inhibitory tone across layers of OFC may contribute to the unrestrained irritability and violent behaviors in common shared by both patients with schizophrenia and bipolar disorder. Nonetheless, our findings indicate the obvious correlations between lamina-specifically altered TrkB and GAD67 mRNA levels in OFC might be a candidate for endophenotype of bipolar disorder.

None Declared

Sleep disturbances are common among adult patients with cancer and their caregivers. To our knowledge, no sleep intervention to date has been designed to be provided to both patients with cancer and their caregivers simultaneously. This single-arm study aimed to pilot test the feasibility and acceptability, and to illustrate the preliminary efficacy on sleep efficiency of the newly developed dyadic sleep intervention, My Sleep Our Sleep (MSOS: NCT04712604).

Adult patients who were newly diagnosed with a gastrointestinal (GI) cancer and their sleep-partner caregivers (n = 20 persons: 10 dyads, 64 years old, 60% female patients, 20% Hispanic, 28 years relationship duration), both of whom had at least mild levels of sleep disturbance (Pittsburgh Sleep Quality Index [PSQI] ≥ 5) participated in this study. MSOS intervention consists of four 1-hour weekly sessions delivered using Zoom to the patient–caregiver dyad together.

We were able to enroll 92.9% of the eligible and screened patient–caregiver dyads within 4 months. Participants reported high satisfaction in 8 domains (average 4.76 on a 1–5 rating). All participants agreed that the number of sessions, interval (weekly), and delivery mode (Zoom) were optimal. Participants also preferred attending the intervention with their partners. Both patients and caregivers showed improvement in sleep efficiency after completing the MSOS intervention: Cohen’s d = 1.04 and 1.47, respectively.

Results support the feasibility and acceptability, as well as provide the preliminary efficacy of MSOS for adult patients with GI cancer and their sleep-partner caregivers. Findings suggest the need for more rigorous controlled trial designs for further efficacy testing of MSOS intervention.

Obsessive-compulsive disorder (OCD) and schizophrenia are often reported as co-morbid conditions. However, the evidence of an association between OCD and the risk of schizophrenia is limited. This study investigated the risk of schizophrenia in patients newly diagnosed with OCD using a nationally representative sample cohort in South Korea.

Data were obtained from the 2002–2013 Korean National Health Insurance Service-National Sample Cohort of the National Health Insurance Service. Using propensity score matching, 2509 patients with OCD and a control group of 7527 patients were included in the analysis. Chi-squared tests were used to investigate and compare the general characteristics of the study population. The risk of schizophrenia was analysed using the Cox proportional hazard model.

The incidence rate was 45.79/10 000 person-year for patients with OCD and 4.19/10 000 person-year for patients without OCD. Patients with OCD had a higher risk of schizophrenia compared to the control group after adjusting for covariates (hazard ratio = 10.46, 95% confidence interval = 6.07–18.00).

This study identified an association between the diagnosis of OCD and the risk of schizophrenia in a South Korean national representative cohort. Further research using a prospective design to clarify the causality of OCD in schizophrenia in a controlled environment should be conducted to validate these findings.

Social anxiety disorder (SAD) can accompany emotional symptoms as well as physical reactions. The assessment and real-time measurement of SAD is difficult in real-world.

This study aims to predict the severity of specific anxiety states and virtual reality (VR) sickness in SAD patients by a machine learning model based on only quantitative measuring of autonomic physiologic signals during VR therapy sessions.

In total, 32 individuals with SAD symptoms were enrolled in VR participatory sessions. We assessed patients’ specific anxiety symptoms through Internalized Shame Scale (ISS) and Post-Event Rumination Scale (PERS), and VR sickness through Simulator Sickness Questionnaire (SSQ). Specific anxiety symptoms and VR sickness were divided into severe and non-severe states based on the total score of each scale by K-means clustering. Logistic regression, Random Forest, Naïve Bayes classifier, and Support Vector Machine were used based on the physiological signal data to predict the severity group in subdomains of ISS, PERS, and SSQ.

Prediction performance (F1 score) for the severity of the ISS mistake anxiety subdomain was higher than other scales with 0.8421. For VR sickness, prediction performance for the severity of the physical subdomain was higher than the non-physical subdomain with 0.7692.

The study findings present that mistake anxiety and physical sickness could be predicted more accurately by only autonomic physiological signals, suggesting these features are probably associated with autonomic responses. Based on the present study results, we could provide the evidence for predicting the severity of specific anxiety or VR adverse effects only based on in-situ physiological signals.

No significant relationships.