The emotion regulation network (ERN) in the brain provides a framework for understanding the neuropathology of affective disorders. Although previous neuroimaging studies have investigated the neurobiological correlates of the ERN in major depressive disorder (MDD), whether patients with MDD exhibit abnormal functional connectivity (FC) patterns in the ERN and whether the abnormal FC in the ERN can serve as a therapeutic response signature remain unclear.

A large functional magnetic resonance imaging dataset comprising 709 patients with MDD and 725 healthy controls (HCs) recruited across five sites was analyzed. Using a seed-based FC approach, we first investigated the group differences in whole-brain resting-state FC of the 14 ERN seeds between participants with and without MDD. Furthermore, an independent sample (45 MDD patients) was used to evaluate the relationship between the aforementioned abnormal FC in the ERN and symptom improvement after 8 weeks of antidepressant monotherapy.

Compared to the HCs, patients with MDD exhibited aberrant FC between 7 ERN seeds and several cortical and subcortical areas, including the bilateral middle temporal gyrus, bilateral occipital gyrus, right thalamus, calcarine cortex, middle frontal gyrus, and the bilateral superior temporal gyrus. In an independent sample, these aberrant FCs in the ERN were negatively correlated with the reduction rate of the HAMD17 score among MDD patients.

These results might extend our understanding of the neurobiological underpinnings underlying unadaptable or inflexible emotional processing in MDD patients and help to elucidate the mechanisms of therapeutic response.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used due to their profound efficacy in glycemic control and weight management. Real-world observations have revealed potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs. This study aimed to comprehensively investigate and characterize these neuropsychiatric AEs with GLP-1RAs.

We analyzed GLP-1RA adverse reaction reports using the FDA Adverse Event Reporting System database. Disproportionality analysis using reporting odds ratio (ROR) identified eight categories of neuropsychiatric AEs associated with GLP-1RAs. We conducted descriptive and time-to-onset (TTO) analyses and explored neuropsychiatric AE signals among individual GLP-1RAs for weight loss and diabetes mellitus (DM) indications.

We identified 25,110 cases of GLP-1RA-related neuropsychiatric AEs. GLP-1RAs showed an association with headache (ROR 1.74, 95% confidence interval [CI] 1.65–1.84), migraine (ROR 1.28, 95%CI 1.06–1.55), and olfactory and sensory nerve abnormalities (ROR 2.44, 95%CI 1.83–3.25; ROR 1.69, 95%CI 1.54–1.85). Semaglutide showed a moderate suicide-related AEs signal in the weight loss population (ROR 2.55, 95%CI 1.97–3.31). The median TTO was 16 days (interquartile range: 3–66 days).

In this study, we identified eight potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs and, for the first time, detected positive signals for migraine, olfactory abnormalities, and sensory abnormalities. We also observed positive suicide-related signals of semaglutide, in weight loss population. This study provides a reliable basis for further investigation of GLP-1RA-related neuropsychiatric AEs. However, as an exploratory study, our findings require confirmation through large-scale prospective studies.

An increasing number of observational studies have reported associations between frailty and mental disorders, but the causality remains ambiguous.

To assess the bidirectional causal relationship between frailty and nine mental disorders.

We conducted a bidirectional two-sample Mendelian randomisation on genome-wide association study summary data, to investigate causality between frailty and nine mental disorders. Causal effects were primarily estimated using inverse variance weighted method. Several secondary analyses were applied to verify the results. Cochran's Q-test and Mendelian randomisation Egger intercept were applied to evaluate heterogeneity and pleiotropy.

Genetically determined frailty was significantly associated with increased risk of major depressive disorder (MDD) (odds ratio 1.86, 95% CI 1.36–2.53, P = 8.1 × 10−5), anxiety (odds ratio 2.76, 95% CI 1.56–4.90, P = 5.0 × 10−4), post-traumatic stress disorder (PTSD) (odds ratio 2.56, 95% CI 1.69–3.87, P = 9.9 × 10−6), neuroticism (β = 0.25, 95% CI 0.11–0.38, P = 3.3 × 10−4) and insomnia (β = 0.50, 95% CI 0.25–0.75, P = 1.1 × 10−4). Conversely, genetic liability to MDD, neuroticism, insomnia and suicide attempt significantly increased risk of frailty (MDD: β = 0.071, 95% CI 0.033–0.110, P = 2.8 × 10−4; neuroticism: β = 0.269, 95% CI 0.173–0.365, P = 3.4 × 10−8; insomnia: β = 0.160, 95% CI 0.141–0.179, P = 3.2 × 10−61; suicide attempt: β = 0.056, 95% CI 0.029–0.084, P = 3.4 × 10−5). There was a suggestive detrimental association of frailty on suicide attempt and an inverse relationship of subjective well-being on frailty.

Our findings show bidirectional causal associations between frailty and MDD, insomnia and neuroticism. Additionally, higher frailty levels are associated with anxiety and PTSD, and suicide attempts are correlated with increased frailty. Understanding these associations is crucial for the effective management of frailty and improvement of mental disorders.

Depressive and anxiety disorders constitute a major component of the disease burden of mental disorders in China.

To comprehensively evaluate the disease burden of depressive and anxiety disorders in China.

The raw data is sourced from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021. This study presented the disease burden by prevalence and disability-adjusted life years (DALYs) of depressive and anxiety disorders at both the national and provincial levels in China from 1990 to 2021, and by gender (referred to as 'sex' in the GBD 2021) and age.

From 1990 to 2021, the number of depressive disorder cases (from 34.4 to 53.1 million) and anxiety disorders (from 40.5 to 53.1 million) increased by 54% (95% uncertainty intervals: 43.9, 65.3) and 31.2% (19.9, 43.8), respectively. The age-standardised prevalence rate of depressive disorders decreased by 6.4% (2.9, 10.4), from 3071.8 to 2875.7 per 100 000 persons, while the prevalence of anxiety disorders remained stable. COVID-19 had a significant adverse impact on both conditions. There was considerable variability in the disease burden across genders, age groups, provinces and temporal trends. DALYs showed similar patterns.

The burden of depressive and anxiety disorders in China has been rising over the past three decades, with a larger increase during COVID-19. There is notable variability in disease burden across genders, age groups and provinces, which are important factors for the government and policymakers when developing intervention strategies. Additionally, the government and health authorities should consider the potential impact of public health emergencies on the burden of depressive and anxiety disorders in future efforts.

Depression is associated with serious disease burden. Despite the multitude of antidepressant options available, the adherence rate is often low. Accounting for patient preferences can potentially boost adherence to antidepressant medication and elevate patient satisfaction. However, limited evidence exists regarding patient preferences for antidepressant selection. This study aims to elicit patient preferences regarding the benefits, risks, and cost attributes of antidepressants in China.

A best-worst scaling profile case experiment was conducted using a face-to-face survey administered to patients diagnosed with depression. Patients were recruited from general and psychiatric hospitals. We utilized a multiphase approach that integrated literature review, expert consultation, and best-worst scaling to develop attributes within choice sets. The attributes with each varying across two or three levels encompassed remission rate, sleep disorders, risk of headache or dizziness, risk of gastrointestinal adverse events, risk of liver or kidney injury, and monthly out-of-pocket costs. Each respondent answered seven choice tasks, including a dominant task. Data were analyzed using conditional logit, mixed logit, and generalized multinomial logit models. Subgroup analyses were conducted to explore preference heterogeneity.

A total of 331 participants completed the survey and met the inclusion criteria. Almost all attribute levels were statistically significant. Overall, the most desirable characteristics of antidepressant medications were higher remission rates (80% and 55% rates; p<0.05), lower risk of liver or kidney injury (1% rate; p<0.05), and fewer monthly out-of-pocket costs (CNY100 [USD13.93, EUR12.75]; p<0.05). Risks of gastrointestinal adverse events (60% and 35% rates) and insomnia were the least preferred features. Regarding attributes, efficacy, the risk of gastrointestinal adverse events, and sleep disorders were relatively important factors influencing patient choice. Preferences differed slightly by age, degree of education, personal annual income, and treatments currently received.

Our study suggests that efficacy, gastrointestinal adverse effects, sleep disorders, and treatment costs are critical drivers behind medication choices among patients with depression. Preference heterogeneity also exists regarding individual and therapeutic characteristics, which need more samples and further analyses to identify. These discoveries hold the potential to enrich the shared decision-making process between physicians and patients within healthcare settings.

Major psychiatric disorders (MPDs) are delineated by distinct clinical features. However, overlapping symptoms and transdiagnostic effectiveness of medications have challenged the traditional diagnostic categorisation. We investigate if there are shared and illness-specific disruptions in the regional functional efficiency (RFE) of the brain across these disorders.

We included 364 participants (118 schizophrenia [SCZ], 80 bipolar disorder [BD], 91 major depressive disorder [MDD], and 75 healthy controls [HCs]). Resting-state fMRI was used to caclulate the RFE based on the static amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality and corresponding dynamic measures indicating variability over time. We used principal component analysis to obtain static and dynamic RFE values. We conducted functional and genetic annotation and enrichment analysis based on abnormal RFE profiles.

SCZ showed higher static RFE in the cortico-striatal regions and excessive variability in the cortico-limbic regions. SCZ and MDD shared lower static RFE with higher dynamic RFE in sensorimotor regions than BD and HCs. We observed association between static RFE abnormalities with reward and sensorimotor functions and dynamic RFE abnormalities with sensorimotor functions. Differential spatial expression of genes related to glutamatergic synapse and calcium/cAMP signaling was more likely in the regions with aberrant RFE.

SCZ shares more regions with disrupted functional integrity, especially in sensorimotor regions, with MDD rather than BD. The neural patterns of these transdiagnostic changes appear to be potentially driven by gene expression variations relating to glutamatergic synapses and calcium/cAMP signaling. The aberrant sensorimotor, cortico-striatal, and cortico-limbic integrity may collectively underlie neurobiological mechanisms of MPDs.

Over the past several decades, more research focuses have been made on the inflammation/immune hypothesis of schizophrenia. Building upon synaptic plasticity hypothesis, inflammation may contribute the underlying pathophysiology of schizophrenia. Yet, pinpointing the specific inflammatory agents responsible for schizophrenia remains a complex challenge, mainly due to medication and metabolic status. Multiple lines of evidence point to a wide-spread genetic association across genome underlying the phenotypic variations of schizophrenia.

We collected the latest genome-wide association analysis (GWAS) summary data of schizophrenia, cytokines, and longitudinal change of brain. We utilized the omnigenic model which takes into account all genomic SNPs included in the GWAS of trait, instead of traditional Mendelian randomization (MR) methods. We conducted two round MR to investigate the inflammatory triggers of schizophrenia and the resulting longitudinal changes in the brain.

We identified seven inflammation markers linked to schizophrenia onset, which all passed the Bonferroni correction for multiple comparisons (bNGF, GROA(CXCL1), IL-8, M-CSF, MCP-3 (CCL7), TNF-β, CRP). Moreover, CRP were found to significantly influence the linear rate of brain morphology changes, predominantly in the white matter of the cerebrum and cerebellum.

With an omnigenic approach, our study sheds light on the immune pathology of schizophrenia. Although these findings need confirmation from future studies employing different methodologies, our work provides substantial evidence that pervasive, low-level neuroinflammation may play a pivotal role in schizophrenia, potentially leading to notable longitudinal changes in brain morphology.