Major depressive disorder (MDD) is a prevalent and disabling condition. Approximately 30-50% of patients do not respond to first-line medication or psychotherapy. Therefore, several studies have investigated the predictive potential of pretreatment severity rating or neuroimaging features to guide clinical approaches that can speed optimal treatment selection.

To evaluate the performance of 1) severity ratings (scores of Hamilton Depression/Anxiety Scale, illness duration, and sleep quality, etc.) and demographic characteristic and 2) brain magnetic resonance imaging (MRI) features in predicting treatment outcomes for MDD. Second, to assess performance variations among varied modalities and interventions in MRI studies.

We searched studies in PubMed, Embase, Web of Science, and Science Direct databases before March 22, 2023. We extracted a confusion matrix for prediction in each study. Separate meta-analyses were performed for clinical and MRI studies. The logarithm of diagnostic odds ratio [log(DOR)], sensitivity, and specificity were conducted using Reitsma’s random effect model. The area under curve (AUC) of summary receiver operating characteristic (SROC) curve was calculated.

Subgroup analyses were conducted in MRI studies based on modalities: resting-state functional MRI (rsfMRI), task-based fMRI (tbfMRI), and structural MRI (sMRI), and interventions: antidepressant (including selective serotonin reuptake inhibitors [SSRI]) and electroconvulsive therapy (ECT). Meta-regression was conducted 1) between clinical and MRI studies and 2) among modality or intervention subgroups in MRI studies.

We included ten studies used clinical features covering 6494 patients, yielded a log(DOR) of 1.42, AUC of 0.71, sensitivity of 0.61, and specificity of 0.74. In terms of MRI, 44 studies with 2623 patients were included, revealing an overall log(DOR) of 2.53. The AUC, sensitivity, and specificity were 0.89, 0.78, and 0.75.

Studies using MRI features had a higher sensitivity (0.89 vs. 0.61) in predicting treatment outcomes than clinical features (P < 0.001). RsfMRI had higher specificity (0.79 vs. 0.69) than tbfMRI subgroup (P = 0.01). No significant differences were found between sMRI and other modalities, nor between antidepressants (SSRIs and others) and ECT. Antidepressant studies primarily identified predictive imaging features in limbic and default mode networks, while ECT mainly focused on limbic network.

Our findings suggest a robust promise for pretreatment brain MRI features in predicting treatment outcomes in MDD, offering higher accuracy than clinical studies. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. For MRI studies, overlapping but distinct network level measures predicted outcomes for antidepressants and ECT.

None Declared

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. It is considered that dysregulation of cytokine levels is related to the pathophysiological mechanism of OCD. However, the results of previous studies on cytokine levels in OCD are inconsistent.

To perform a meta-analysis assessing cytokine levels in peripheral blood of OCD patients.

We searched in PubMed, Web of Science, and Embase from inception to March 31, 2023 for eligible studies. We conducted multivariate meta-analysis in combined proinflammatory cytokines (interleukin-6 [IL-6], IL-1β, IL-2, tumor necrosis factor-α [TNF-α], and interferon-γ [IFN-γ]) and combined anti-inflammatory cytokines (IL-10 and IL-4) respectively, and calculated the same meta-analysis in each cytokine. We also performed sensitivity analysis and publication bias tests, as well as subgroup analysis (i.e. different age groups, varied cytokine measurement methods, medication treated or naïve, and presence of psychiatric comorbidities) and meta-regression analysis (variables including patients’ sex ratio, age, age at symptom onset, illness duration, scores of Y-BOCS, family history of psychiatric disorders, and BMI).

17 original studies (13, 13, 10, 5, 4, 3, 2 studies for IL-6, TNF-α, IL-1β, IL-10, IL-2, IL-4, and IFN-γ, respectively), 573 patients (mean age, 25.2; 50.3% female) and 498 healthy controls (HC; mean age, 25.3; 51.4% female) were included. The results showed that the levels of combined pro- or anti-inflammatory cytokines and each signle cytokine were not significantly different between OCD patients and HC (all P>0.05), with significant heterogeneities in all analyses (I2 from 79.1% to 91.7%). We did not find between-group differences in cytokine levels in all subgroup analyses. Meta-regression analysis suggested that age at onset (P=0.0003) and family history (P=0.0062) might be the source of heterogeneity in TNF-α level. Sensitivity analysis confirmed that all results were stable, except for IL-4 where different cytokine measurement methods may be the contributing factor. Egger test did not find publication bias.

Our study showed no difference in cytokine levels between OCD patients and HC, but age at onset and family history may affect TNF-α level. Confounding factors such as age at onset, family history, and cytokine measurement methods should be controlled in future studies to further explore the immune mechanism of OCD.

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Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.

This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.

We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.

Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.

These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.

None Declared

The concept of Mental Health Literacy (MHL) is inherently multidimensional. However, the interrelationships among its various dimensions remain insufficiently elucidated. In recent years, the textual analysis of social media posts has emerged as a promising methodological approach for longitudinal research in this domain.

This study aimed to investigate whether temporal causal associations exist between recognition of mental illness (R), mental illness stigma (S), help-seeking efficacy (HE), maintenance of positive mental health (M), and help-seeking attitude (HA).

Tweets were collocted at three distinct time points: T1, T2, and T3, spanning the period from November 1, 2021, to December 31, 2022. We employed a machine-learning approach to categorize the posts into five MHL facets. Using these facets, we trained a machine learning model, specifically Bidirectional Encoder Representations from Transformers (BERT), to determine the MHL scores. To be eligible, an account must have an R facet score at T1, and M, S, HE facet scores at T2, as well as an HA facet score at T3. In total, we retrieved 4,471,951 MHL-related tweets from 941 users. We further employed structural equation modeling to validate the causal relationships within the MHL framework.

In the evaluation, BERT achieved average accuracy scores exceeding 89% across the five MHL facets in the validation set, along with F1-scores ranging between 0.75 and 0.89. Among the five MHL facets—maintenance of positive mental health, recognition of mental illness, help-seeking efficacy, and help-seeking attitudes—each demonstrated a statistically significant positive correlation with the others. Conversely, mental illness stigma exhibited a statistically significant negative correlation with the remaining four facets. In the analysis using single-mediation models, each of the individual mediator variables—namely, mental illness stigma, help-seeking efficacy, and maintenance of positive mental health—exhibited significant indirect effects. In the multiple-mediation model, two mediator variables—help-seeking efficacy and maintenance of positive mental health—demonstrated significant indirect effects. These findings suggested that the recognition of mental illness exerted an influence on help-seeking attitudes through one or more of these mediators.

By leveraging machine learning techniques for the textual analysis of social media and employing a longitudinal research design with panel data, this study elucidates the potential mechanisms through which the MHL framework influences attitudes toward seeking mental health services. These insights hold significant implications for the design of future interventions and the development of targeted policies aimed at promoting help-seeking behaviors.

None Declared

There’s large heterogeneity present in major depressive disorder (MDD) and controversial evidence on alterations of brain functional connectivity (FC), making it hard to elucidate the neurobiological basis of MDD. Subtyping is one promising solution to characterize this heterogeneity.

To identify neurophysiological subtypes of MDD based on FC derived from resting-state functional magnetic resonance imaging using large multisite data and investigate the differences in genetic mechanisms and neurotransmitter basis of FC alterations, and the differences of FC-related cognition between each subtype.

Consensus clustering of FC patterns was applied to a population of 829 MDD patients from REST-Meta-MDD database after data cleaning and image quality control. Gene transcriptomic data derived from Allen Human Brain Atlas and neurotransmitter receptor/transporter density data acquired by using neuromap toolbox were used to characterize the molecular mechanism underlying each FC-based subtype by identifying the gene set and neurotransmitters/transporters showing high spatial similarity with the profiles of FC alterations between each subtype and 770 healthy controls. The FC-related cognition in each subtype was also selected by lasso regression.

Two stable neurophysiological MDD subtypes were found and labeled as hypoconnectivity (n=527) and hyperconnectivity (n=299) characterized by the FC differences in each subtype relative to controls, respectively. The two subtypes did not differ in age, sex, and scores of Hamilton Depression/Anxiety Scale.

The genes related to FC alterations were enriched in ion transmembrane transport, synaptic transmission/organization, axon development, and regulation of neurotransmitter level for both subtypes, but specifically enriched in glial cell differentiation for hypoconnectivity subtype, while enriched in regulation of presynaptic membrane and regulation of neuron differentiation for hyperconnectivity subtype.

FC alterations were associated with the density of 5-HT2a receptor in both subtypes. For hyperconnectivity subtype, FC alterations were also correlated with the density of norepinephrine transporter, glutamate receptor, GABA receptor, 5-HT1b receptor, and cannabinoid receptor.

Both subtypes showed correlations between FC and categorization, motor inhibition, and localization. The FC in hypoconnectivity subtype correlated with response inhibition, selective attention, face recognition, sleep, empathy, expertise, uncertainty, and anticipation, while that was related to inference, speech perception, and reward anticipation in hyperconnectivity subtype.

Our findings suggested the presence of two neuroimaging subtypes of MDD characterized by hypo or hyper-connectivity. The two subtypes had both shared and distinct genetic mechanisms, neurotransmitter receptor/transporter profiles, and cognition types.

None Declared

Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.

This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.

Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).

Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

Three factors converge to underscore the heightened importance of evaluating the potential health/well-being effects of friendships in older adulthood. First, policymakers, scientists, and the public alike are recognizing the importance of social relationships for health/well-being and creating national policies to promote social connection. Second, many populations are rapidly aging throughout the world. Third, we currently face what some call a ‘friendship recession’. Although, growing research documents associations between friendship with better health and well-being, friendship can also have a ‘dark side’ and can potentially promote negative outcomes. To better capture friendship’s potential heterogeneous effects, we took an outcome-wide analytic approach.

We analysed data from 12,998 participants in the Health and Retirement Study (HRS) – a prospective and nationally representative cohort of U.S. adults aged >50, and, evaluated if increases in friendship strength (between t0; 2006/2008 and t1; 2010/2012) were associated with better health/well-being across 35 outcomes (in t2; 2014/2016). To assess friendship strength, we leveraged all available friendship items in HRS and created a composite ‘friendship score’ that assessed the following three domains: (1) friendship network size, (2) friendship network contact frequency and (3) friendship network quality.

Stronger friendships were associated with better outcomes on some indicators of physical health (e.g. reduced risk of mortality), health behaviours (e.g. increased physical activity) and nearly all psychosocial indicators (e.g. higher positive affect and mastery, as well as lower negative affect and risk of depression). Friendship was also associated with increased likelihood of smoking and heavy drinking (although the latter association with heavy drinking did not reach conventional levels of statistical significance).

Our findings indicate that stronger friendships can have a dual impact on health and well-being. While stronger friendships appear to mainly promote a range of health and well-being outcomes, stronger friendships might also promote negative outcomes. Additional research is needed, and any future friendship interventions and policies that aim to enhance outcomes should focus on how to amplify positive outcomes while mitigating harmful ones.

Excessive and persistent fear of clusters of holes, also known as trypophobia, has been suggested to reflect cortical hyperexcitability and may be associated with mental health risks. No study, however, has yet examined these associations in representative epidemiological samples.

To examine the prevalence of trypophobia in a population-representative youth sample, its association with mental health and functioning, and its interaction with external stress.

A total of 2065 young people were consecutively recruited from a household-based epidemiological youth mental health study in Hong Kong. Trypophobia, symptoms of anxiety, depression and stress, and exposure to personal stressors were assessed. Logistic regression was used to assess the relationships between trypophobia and mental health. Potential additive and interaction effects of trypophobia and high stress exposure on mental health were also tested.

The prevalence of trypophobia was 17.6%. Trypophobia was significantly associated with severe symptoms of anxiety (odds ratio (OR) = 1.83, 95% CI = 1.32–2.53), depression (OR = 1.78, 95% CI = 1.24–2.56) and stress (OR = 1.68, 95% CI = 1.11–2.53), even when accounting for sociodemographic factors, personal and family psychiatric history, resilience and stress exposure. Dose–response relationships were observed, and trypophobia significantly potentiated the effects of stress exposure on symptom outcomes, particularly for depressive symptoms. Those with trypophobia also showed significantly poorer functioning across domains and poorer health-related quality of life.

Screening for trypophobia in young people may facilitate early risk detection and intervention, particularly among those with recent stress exposure. Nevertheless, the generally small effect sizes suggest that other factors have more prominent roles in determining recent mental health outcomes in population-based samples; these should be explored in future work.

Undergraduate students encounter developmental challenges during their transition into adulthood. Previous studies have claimed that adults with later chronotypes usually manifest negative psychological effects: poor sleep quality, greater stress, depression, and cognitive dysfunction. However, knowledge about the relationship between chronotype, stress, and sleep quality among young adults is lacking.

The present study investigated the relationship between undergraduates’ chronotypes and perceived stress on sleep quality.

An online survey with a descriptive, cross-sectional design was conducted with a convenience sample of undergraduate students at a university in southern Taiwan. Those who were 20-25 years old and enrolled as a student were included; but who had been suspended or had deferred graduation were excluded. Students’ chronotype, stress, and sleep quality were assessed with three self-reported instruments: Munich Chronotype Questionnaire (MCTQ), Perceived Stress Scale (PSS), and Pittsburgh Sleep Quality Index (PSQI).

Of 161 undergraduates who completed the questionnaires, 51 reported using an alarm clock to wake and were removed from data analysis. One hundred and ten students’ mean age is 20.3 and perceived moderate stress. Sixty-one percent were poor-quality sleepers. The mean chronotype score was 5.7, and 85.5% had an intermediate chronotype, while 13.6% had an evening chronotype. Chronotype and perceived stress were positively correlated with sleep quality (p < .001). Social jetlag was positively correlated with chronotype (p =.036). Undergraduate’s later chronotype and higher stress perception predicted 30% of poorer sleep quality (p < .001).

Undergraduate students’ chronotype and perceived stress were positively correlated and acted as predictors of the sleep quality. The findings could help to develop health-promotion interventions for these emerging adults to adjust their daily routines; and reduce their social jetlag, stress levels, and sleep disturbance.

None Declared