European Archives Of Psychiatry And Clinical Neuroscience[JOURNAL]
Sun
200 papers
Abnormal emotional intensity processing in individuals at clinical high risk for psychosis: evidence from event-related potentials.
Wei A, Fan M, Liu T … +5 more , Gao R, Luan P, Sun S, Kong L, He X
Eur Arch Psychiatry Clin Neurosci · 2026 Jul · PMID 42400657 · Publisher ↗
BACKGROUND: Social cognitive impairment is a key vulnerability marker for psychosis and is commonly observed in individuals at clinical high risk (CHR). However, the neurophysiological mechanisms underlying abnormalities...
BACKGROUND: Social cognitive impairment is a key vulnerability marker for psychosis and is commonly observed in individuals at clinical high risk (CHR). However, the neurophysiological mechanisms underlying abnormalities in emotional intensity processing remain unclear. This study investigated behavioral and electrophysiological responses to emotional intensity in CHR individuals using an event-related potential (ERP) paradigm. METHODS: Thirty CHR participants, 29 healthy controls (HCs), and an exploratory sample of 30 individuals with schizophrenia (SCZ) completed the Emotional Intensity Recognition Task (EIRT) during high-density EEG recording. Behavioral measures included reaction time (RT) and accuracy and were analyzed across six basic emotional categories. ERP components, including N100, N170, P200, P300, and LPP, were analyzed across predefined frontal, central, parietal, and occipital regions. ERP analyses also included neutral expressions because identifiable EEG event markers were available. Associations between ERP indices, behavioral performance, and clinical symptoms were also examined. RESULTS: CHR individuals showed significantly slower RTs than HCs across emotional conditions, while accuracy remained comparable. ERP analyses, including neutral expressions where EEG markers were available, revealed altered modulation of emotional face processing across multiple temporal stages. Group-related effects were most consistently observed for P300 amplitude and LPP latency, suggesting atypical attentional allocation and late evaluative processing in CHR individuals. Exploratory correlation analyses suggested associations between selected ERP indices and clinical symptoms; however, these findings were not corrected for multiple comparisons and should be interpreted cautiously. Exploratory unadjusted comparisons with the SCZ group suggested group differences in selected ERP measures, but these findings should be interpreted cautiously because the SCZ group was older and was not collected concurrently with the primary CHR and HC samples. CONCLUSIONS: Individuals at clinical high risk for psychosis exhibit slowed behavioral responses and altered ERP modulation during emotional intensity processing. These findings suggest that the EIRT-ERP paradigm may help characterize social-cognitive and neurophysiological alterations in the psychosis prodrome. Larger longitudinal studies are needed to determine whether these ERP measures have predictive value for functional outcomes or transition to psychosis.
The role of attention in perceptual biases in patients with schizophrenia spectrum disorder and healthy controls.
Schütz AC, Bolat O, Kori K … +2 more , Kircher T, Straube B
Eur Arch Psychiatry Clin Neurosci · 2026 Jul · PMID 42400656 · Publisher ↗
Ambiguous or uncertain sensory information is often resolved by incorporating prior assumptions about the most likely interpretation. Similar neural structures and a common visual environment typically lead to homogeneou...
Ambiguous or uncertain sensory information is often resolved by incorporating prior assumptions about the most likely interpretation. Similar neural structures and a common visual environment typically lead to homogeneous priors in the population. Ambiguous motion displays are a rare exception as sustained idiosyncratic directional preferences have been observed. Patients with schizophrenia spectrum disorder (SSD) have been shown to rely less on perceptual priors in some contexts, yet their idiosyncratic directional preferences in ambiguous motion perception remain unexplored. Directional preferences were measured in two ambiguous displays: apparent motion and transparency-from-motion. To assess the strength and temporal stability of these preferences, we conducted measurements at two time points: first, during the acute phase of SSD in 32 hospitalized patients, and second, after symptom remission. A matched group of 18 healthy controls was also tested at comparable intervals. We found that patients exhibit idiosyncratic directional preferences that are similar in strength and stability as in healthy observers. Across patients and controls, the preference strength was positively correlated with performance in the d2-test, which measures selective and sustained attention. Apart from that, there was no evidence that the severity of positive or negative symptoms across time or the performance in a visuo-spatial working memory task would be related to the directional preferences. These findings suggest that certain perceptual priors can be preserved in SSD, regardless of symptom status, with attentional resources playing a crucial role in determining the strength and stability of directional preferences.
Effects of quetiapine on cognitive functioning in schizophrenia: evidence for the remyelination hypothesis?
Ising M, Raabe F, Fischer L … +30 more , Schmitt A, Sämann P, Adorjan K, Anghelescu IG, Arolt V, Baune BT, Dannlowski U, Dietrich DE, Fallgatter AJ, Figge C, Heilbronner M, Jäger M, Juckel G, Konrad C, Navarro-Flores A, Kohshour MO, Reich-Erkelenz D, Reimer J, Reininghaus EZ, Schmauß M, Schulte EC, Senner F, Spitzer C, Wiltfang J, Zimmermann J, Schulze TG, Heilbronner U, Budde M, Papiol S, Falkai P
Eur Arch Psychiatry Clin Neurosci · 2026 Jul · PMID 42400655 · Publisher ↗
Postmortem findings, neuroimaging data, and in-vitro models suggest a decrease in number and density of oligodendrocytes is driving cognitive deficits in schizophrenia (SCZ). Second-generation antipsychotics are discusse...
Postmortem findings, neuroimaging data, and in-vitro models suggest a decrease in number and density of oligodendrocytes is driving cognitive deficits in schizophrenia (SCZ). Second-generation antipsychotics are discussed to improve oligodendrocyte dysfunction with most conclusive evidence available for quetiapine (QET). We postulate that sustained QET treatment leads to cognitive improvement in SCZ, particularly, in tests with high demands for working memory function. We further hypothesize that these effects are moderated by polygenic factors associated with hippocampus-related brain volumes, general white matter integrity, and/or oligodendroglia-related SCZ risk. Using data of the prospective PsyCourse study, we identified 166 patients with SCZ spectrum disorder receiving QET at one or two consecutive visits plus 166 matched patients without QET. Polygenic scores were calculated for subcortical brain volumes, measures of white matter integrity, and for cell type-specific genetic SCZ risks. QET treatment was consistently associated with improved cognitive function independent of time, specifically, in tests with high, but not with low to medium working memory load. Polygenic analyses did not reveal significant moderation effects. In contrary, low genetic SCZ risk specific for genes related to human oligodendrocyte function was associated with higher cognitive performance independent from QET. While we observed improved cognitive performance under QET in high working memory tests, we did not find evidence that polygenic factors associated with hippocampus-related brain volumes, white matter integrity, or oligodendroglia-related SCZ risk moderate this association. Thus, our tentative findings do not provide evidence for the hypothesis that polygenic estimates of hippocampal remyelination capacities influence the association between QET and cognitive performance in SCZ.
Effects of xanomeline-trospium on the gut-lung microbiota axis and susceptibility to LPS-induced acute lung injury in male and female mice.
Ding X, Eguchi A, Murayama R … +4 more , Cai Y, Yue Y, Yang JJ, Hashimoto K
Eur Arch Psychiatry Clin Neurosci · 2026 Jul · PMID 42400654 · Publisher ↗
Xanomeline-trospium is a first-in-class muscarinic receptor-based antipsychotic that improves schizophrenia symptoms without dopamine D receptor antagonism. Although gastrointestinal (GI) adverse effects have been report...
Xanomeline-trospium is a first-in-class muscarinic receptor-based antipsychotic that improves schizophrenia symptoms without dopamine D receptor antagonism. Although gastrointestinal (GI) adverse effects have been reported, its broader effects on host microbiota and susceptibility to respiratory injury remain unclear. We investigated the effects of xanomeline and xanomeline-trospium on gut and lung microbiota, host metabolism, and outcomes in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in male and female mice. Adult mice received vehicle, xanomeline, or xanomeline-trospium for 15 days. Body weight was monitored longitudinally, fecal output was measured, gut and lung microbiota were profiled using 16S rRNA sequencing, and untargeted serum metabolomics was performed using UPLC-QTOF/MS. ALI was induced by intratracheal LPS administration, and survival was assessed for seven days. Xanomeline induced weight loss in female mice and constipation in both sexes, and these effects were attenuated by trospium co-administration. Xanomeline-trospium was associated with sex- and region-associated alterations in gut microbiota, with greater remodeling in the cecum and colon, and also altered lung microbiota composition in both sexes. Integrated multi-omics analyses revealed sex-associated links among specific bacterial taxa, circulating metabolites, and host phenotypes. In the ALI model, xanomeline-trospium significantly increased LPS-induced mortality in female mice but not in male mice; however, formal interaction analysis did not support a significant sex-dependent treatment effect. These findings suggest that xanomeline-trospium alters gut-lung microbiota and host metabolic networks and may influence respiratory vulnerability.
Association of the red blood cell distribution width-to-albumin ratio with incident depression and depressive symptom trajectories in older adults.
Jiang Z, Cai X, Tang F … +2 more , Zhao Z, Lin H
Eur Arch Psychiatry Clin Neurosci · 2026 Jul · PMID 42400653 · Publisher ↗
BACKGROUND: The ratio of red blood cell distribution width to albumin (RAR) is a systemic blood-based marker associated with adverse health outcomes. Although cross-sectional studies have suggested a link between RAR and...
BACKGROUND: The ratio of red blood cell distribution width to albumin (RAR) is a systemic blood-based marker associated with adverse health outcomes. Although cross-sectional studies have suggested a link between RAR and depression, its longitudinal association with the incidence and long-term course of late-life depression has not yet been established. We aimed to address this knowledge gap using data from a large cohort of older adults. METHODS: This longitudinal cohort study used data from the Health and Retirement Study (2016-2022). The analysis of incident depression included 6,151 U.S. adults aged ≥ 60 years who were free of depression at baseline. Multivariable Cox regression was used to assess the association, and restricted cubic splines were applied to examine the dose-response relationship. In a subcohort of 5,588 participants, group-based trajectory modeling was used to identify depressive symptom trajectories, and their association with baseline RAR was examined using multinomial logistic regression. RESULTS: During a median follow-up of 6 years, 1,287 participants developed incident depression. In the fully adjusted model, each 1-unit increase in baseline RAR was associated with a 19% higher risk of incident depression (HR = 1.19; 95% CI: 1.06-1.33). Compared with the lowest quartile, the highest RAR quartile was associated with a higher risk of incident depression (HR = 1.20; 95% CI: 1.01-1.42). The dose-response analysis indicated a linear relationship (P for non-linearity = 0.961). Four distinct symptom trajectories were identified: "Non-depressed" (28.11%), "Low-stable" (40.89%), "Moderate-progressive" (25.42%), and "High-progressive" (5.58%). Compared with the "Non-depressed" group, higher baseline RAR was associated with greater odds of membership in the "High-progressive" (OR = 1.31; 95% CI: 1.11-1.55) and "Moderate-progressive" (OR = 1.36; 95% CI: 1.07-1.73) groups. CONCLUSION: In this large, nationally representative cohort of older adults, higher baseline RAR was longitudinally associated with an increased risk of incident depression and a subsequent long-term trajectory of worsening depressive symptoms.
Major depressive disorder-alcohol use disorder comorbidity: diagnosis, mechanisms and treatment.
Fang B, Hua H, Chen W … +5 more , Cheng S, Xiong Y, Zhu Z, Lu J, Wu Y
Eur Arch Psychiatry Clin Neurosci · 2026 Jul · PMID 42384049 · Publisher ↗
Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD) are two highly prevalent psychiatric disorders with a high comorbidity rate, which is significantly higher rate than other combinations of mental disorders a...
Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD) are two highly prevalent psychiatric disorders with a high comorbidity rate, which is significantly higher rate than other combinations of mental disorders and substance use disorders. This comorbidity not only imposes a substantial disease burden on individuals but also significantly complicates clinical management, leading to more severe functional impairment, reduced treatment adherence, and increased resistance to monotherapy. AUD diagnosis varies by diagnostic system: DSM-V integrates alcohol dependence and abuse into 11 criteria with severity grading, while ICD-11 retains two subtypes and shows higher diagnostic rates for dependence. MDD, the depressive subtype with the highest AUD comorbidity rate, must be distinguished from alcohol-induced depression. Underlying mechanisms of this comorbidity involve bidirectional pathways as well as core pathophysiological processes including abnormal reward sensitivity, neurotrophic-inflammatory imbalance, dysregulation of neurotransmitter systems and the hypothalamic-pituitary-adrenal (HPA) axis, gut-brain axis disruption, and shared risk factors. Therapeutic strategies encompass multiple modalities: pharmacological interventions include selective serotonin reuptake inhibitors (SSRIs) combined with AUD-targeted therapies, as well as emerging agents like extended-release trazodone and ketamine; psychosocial interventions are dominated by cognitive behavioral therapy (CBT); physical therapies such as repetitive transcranial magnetic stimulation (rTMS) and gut-brain axis-targeted therapies also show therapeutic potential. Notably, integrated treatment models that simultaneously address both disorders have been proven to outperform sequential or parallel approaches. This review systematically synthesizes the latest evidence on the diagnosis, underlying mechanisms, and therapeutic strategies of AUD-MDD comorbidity, aiming to provide evidence-based references for clinical management.
The interplay between mental health, ecological factors, and problematic smartphone use: a network analysis in adolescents with major depressive disorder.
Liu Y, Shi Y, Yan N … +8 more , Wang L, Li G, Liu Z, Xu H, Huang W, Meng L, Zhou Y, Kroon E
Eur Arch Psychiatry Clin Neurosci · 2026 Jul · PMID 42384048 · Publisher ↗
Adolescence is a critical period for the onset of major depressive disorder (MDD), during which emotional symptoms frequently co-occur with environmental adversity and maladaptive behavioral coping. In China, these proce...
Adolescence is a critical period for the onset of major depressive disorder (MDD), during which emotional symptoms frequently co-occur with environmental adversity and maladaptive behavioral coping. In China, these processes may be further shaped by left-behind experience (LBE) - a prevalent structural vulnerability in which children grow up separated from migrating parents. To clarify these relationships, we applied network analysis in a clinical sample of 2341 adolescents (Mage = 14.99 years,77.92% female) with MDD. Participants were recruited from 14 psychiatric outpatient clinics across China. The networks examined associations among mental health symptoms (depression, anxiety, stress, sleep problems, self-esteem, loneliness), ecological factors (childhood trauma, peer victimization, social support), and problematic smartphone use (PSU). We further examined whether network topology differed by LBE (19.99% of the sample). In the full sample network, depression and loneliness demonstrated the highest strength centrality, while sleep exhibited the lowest. Loneliness and PSU acted as bridges between mental health symptoms and ecological factors. Network comparison tests revealed no significant between-group global structural differences. Although childhood trauma and PSU appeared more centrally positioned in the left-behind group and social support showed slightly higher centrality in the non-left-behind network, these subtle trends need further confirmation. These findings underscore critical psychological-ecological-behavioral interaction pathways in adolescents with MDD, and suggest loneliness and PSU as promising targets for bridge-informed clinical intervention.
The monocyte-to-HDL cholesterol ratio (MHR) modifies the association between dietary patterns and depression: a sex-specific analysis.
Huang Y, Yao K
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42377485 · Publisher ↗
OBJECTIVES: Inflammation and metabolic dysregulation are increasingly considered as key contributors to depression. However, the role of inflammatory-metabolic status in the association between diet quality and depressio...
OBJECTIVES: Inflammation and metabolic dysregulation are increasingly considered as key contributors to depression. However, the role of inflammatory-metabolic status in the association between diet quality and depression remains unclear. This study aimed to investigate whether inflammatory-metabolic status, as reflected by the monocyte-to-high-density lipoprotein cholesterol ratio (MHR), modifies the association between dietary patterns and depression, with a focus on potential sex-specific differences. METHODS: Adults participating in the US National Health and Nutrition Examination Survey (NHANES) 2005-2018 were included. Diet quality was evaluated using four dietary indices: the Healthy Eating Index-2020 (HEI-2020), Dietary Inflammatory Index (DII), Alternative Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH). Depressive symptoms were evaluated using the nine-item Patient Health Questionnaire (PHQ-9). Weighted multivariable logistic regression and restricted cubic spline (RCS) models were used to examine independent and joint associations between dietary patterns, MHR, and depression. Interaction effects between dietary patterns and MHR were assessed on both multiplicative and additive scales. Stratified analyses were conducted to examine the robustness of the results across subgroups. RESULTS: A total of 26,289 participants were included. A positive association between MHR and depression was found in women (OR = 1.61, 95% CI: 1.14-2.28), but not in men. Healthier dietary patterns, reflected by higher HEI-2020 and aMED scores, and lower DII scores, were associated with significantly lower odds of depression in both sexes. RCS analyses indicated a dose-response relationship between dietary pattern scores (HEI-2020, aMED, and DII) and depression. Joint analyses showed that women with both low MHR and high diet quality had the lowest odds of depression. The adjusted ORs were 0.54 (95% CI: 0.42-0.68) for HEI-2020, 0.33 (95% CI: 0.24-0.47) for DII, and 0.55 (95% CI: 0.42-0.71) for aMED. Notably, among women with low MHR, healthier dietary patterns were strongly associated with lower depression odds (HEI-2020: OR = 0.59, 95% CI: 0.44-0.79; DII: OR = 0.38, 95% CI: 0.26-0.55; aMED: OR = 0.62, 95% CI: 0.46-0.84), whereas these associations were weaker among those with high MHR (HEI-2020: OR = 0.75, 95% CI: 0.60-0.95; DII: OR = 0.79, 95% CI: 0.56-1.12; aMED: OR = 0.81, 95% CI: 0.62-1.06). A significant interaction between the DII and MHR on depression was observed in females (multiplicative interaction OR = 0.44, 95% CI: 0.25-0.75). Conversely, among men, the associations between dietary patterns and depression appeared largely independent of MHR status. CONCLUSIONS: The associations between dietary patterns and depression differed across MHR levels in a sex-specific manner. A significant interaction between DII and MHR suggests that inflammatory-metabolic status may be involved in the diet - depression association.
Ictal electroencephalography and heart rate as treatment criteria in electroconvulsive therapy: a systematic review of the literature.
Dilopoulos I, Nickl-Jockschat T, Grözinger M
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42377484 · Publisher ↗
BACKGROUND: Decades before the emergence of precision medicine, psychiatrists raised the question of whether specific seizure characteristics could help optimize electroconvulsive therapy (ECT), as relationships between...
BACKGROUND: Decades before the emergence of precision medicine, psychiatrists raised the question of whether specific seizure characteristics could help optimize electroconvulsive therapy (ECT), as relationships between some of these characteristics and better outcomes were found. From 1990 onward, researchers focused on electroencephalography (EEG) and cardiovascular markers, which were broadly adopted by guidelines worldwide. However, the prognostic value of these markers is still controversial. Here, we provide a systematic summary of the studies on this topic. METHODS: We conducted a literature review on the use of ictal EEG and heart rate as outcome predictors in ECT using the PubMed, EMBASE, Cochrane and PsycINFO databases. RESULTS: Thirty-seven studies addressing more than 100 quality markers fulfilled our inclusion criteria. Single EEG markers were assigned to five categories (postictal inhibition, amplitude, coherence, regularity, and seizure duration). Heart rate and composite markers were considered separately. In contrast to single EEG markers, heart rate and composite markers could be consistently linked to better outcomes in patients with depression. Only a few studies on schizophrenia could be retrieved. CONCLUSION: Multiparametric markers outperformed single markers. Furthermore, changes in heart rate during seizures were related to better outcomes. Although clinical assessment remains the cornerstone of treatment guidance decisions, EEG and cardiac monitoring could help prevent insufficient seizures during the period preceding clinical improvement. Evidence on schizophrenia remains limited. More randomized trials are needed to analyze the role of composite markers as prognostic tools.
Esketamine multi-omic biomarker evaluation in major depressive disorder (EMBER-MDD): concept, objectives and methodologies of a non-clinical investigator-initiated study.
Hohoff C, Lange T, Steinbach L … +3 more , Wissing SM, Van Assche E, Baune BT
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42377483 · Publisher ↗
Treatment resistance (TR) in major depressive disorder (MDD) affects a substantial minority of patients and is hard to recognize early, delaying intensified care. The Esketamine multi-omic biomarker evaluation in MDD (EM...
Treatment resistance (TR) in major depressive disorder (MDD) affects a substantial minority of patients and is hard to recognize early, delaying intensified care. The Esketamine multi-omic biomarker evaluation in MDD (EMBER-MDD) is a non-interventional, investigator-initiated, in-vitro study within the EU Psych-STRATA programme, analyzing biospecimens collected in the randomized INTENSIFY study and the mirror OBS-TR cohort after participants complete treatment. EMBER-MDD aims to discover individual-omic and integrated multi-omic (hypothesis-free) biomarkers and signatures associated with TR risk, and molecular correlates of clinical response to esketamine nasal spray versus treatment as usual (TAU). Biomaterials will derive from approximately 420 adults with MDD (estimated n = 210 esketamine; n = 210 TAU) and include whole blood, RNA-stabilized whole blood, plasma and serum, sampled at baseline and, when feasible, during and after treatment (up to ~ 5,040 aliquots stored at - 80 °C). Genomics will use baseline DNA genotyping on Illumina Infinium GSA v3.0+MD arrays; epigenomics will profile genome-wide DNA methylation across time points using MethylationEPIC v2.0; transcriptomics will employ mRNA-seq (NovaSeq X/ X Plus); and proteomics/ metabolomics will be generated using high-throughput Olink and/ or Biocrates platforms. Each layer will undergo state-of-the-art preprocessing and analyses (e.g., GWAS/ PRS, EWAS, differential expression, WGCNA, pathway and network analyses), followed by integrative strategies including QTL mapping (meQTL/ eQTL/ pQTL/ mQTL) and intermediate-fusion machine learning with nested cross-validation, explainable AI (SHAP/ LIME) and treatment-effect modelling. All outputs are research-only and will not support individual efficacy, tolerability, or clinical decision-making. The study will deliver robust biosignatures and mechanistic hypotheses to guide future validation and inform stratified, molecularly guided intervention strategies in subsequent prospective trials. Trial registration number: 2023-506617-21-00 and 2025-178-f-S.
Differential burden of five major mental disorders in the United States across the COVID-19 pandemic.
Jin Z
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42377482 · Publisher ↗
OBJECTIVE: This study aimed to simultaneously characterize the long-term burden trajectories of five major mental disorders across all US states from 1990 to 2023, including their responses to the COVID-19 pandemic. METH...
OBJECTIVE: This study aimed to simultaneously characterize the long-term burden trajectories of five major mental disorders across all US states from 1990 to 2023, including their responses to the COVID-19 pandemic. METHODS: Age-standardized prevalence and years lived with disability rates for five mental disorders [anxiety disorders, major depressive disorder (MDD), dysthymia, bipolar disorder, and schizophrenia] were analyzed across US states from 1990 to 2023 using Global Burden of Disease Study data, stratified by sex and age, examining temporal trends, pandemic-period changes, geographic distributions, Socio-demographic Index (SDI) correlations, and cross-disorder associations. RESULTS: From 1990 to 2023, anxiety disorders and MDD prevalence increased by 25.4% and 55.2%, while dysthymia (-6.7%), bipolar disorder (-1.0%), and schizophrenia (-5.3%) declined modestly; in 2023, female prevalence of anxiety disorders and MDD exceeded male rates by 77.1% and 79.3%. During 2019-2023, anxiety disorders and MDD prevalence surged by 47.9% and 23.7%, reversing pre-pandemic declining trends of -1.2% and -1.8%, yielding between-period differences of +49.2 and +25.6 percentage points, universally across all 51 states. MDD exhibited the widest disparity, ranging from 2291 per 100,000 in North Dakota to 4803 per 100,000 in West Virginia. SDI was inversely associated with anxiety disorders (ρ = -0.335) and MDD (ρ = -0.355), but positively associated with schizophrenia (ρ = 0.689; all P < 0.05). State-level schizophrenia prevalence was negatively associated with MDD (β = -57.252, P = 0.007) and anxiety disorders (β = -19.597, P = 0.006). CONCLUSION: The COVID-19 pandemic selectively accelerated anxiety and depressive disorder burden across all US states. Substantial geographic disparities, disorder-specific sociodemographic gradients, and cross-disorder ecological patterns were identified.
Exploring the genetic correlation between inflammatory bowel disease and psychiatric disorders: insights from genome-wide association studies.
Zhang J, Shen J, Liu L
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42362821 · Publisher ↗
BACKGROUND: Inflammatory bowel disease (IBD) and psychiatric disorders exhibit complex comorbid patterns, with anxiety and depressive disorders being significantly more prevalent in IBD patients compared to the general p...
BACKGROUND: Inflammatory bowel disease (IBD) and psychiatric disorders exhibit complex comorbid patterns, with anxiety and depressive disorders being significantly more prevalent in IBD patients compared to the general population. These comorbidities may differ between Crohn's disease (CD) and ulcerative colitis (UC), suggesting heterogeneous but potentially shared genetic mechanisms mediated through the gut-brain axis (GBA). OBJECTIVE: To systematically investigate global and local genetic correlations between IBD and eight psychiatric disorders and to identify shared pathogenic mechanisms underlying these comorbidities. METHODS: Using publicly available large-scale GWAS summary statistics, including a meta-analysis of 486,601 individuals for IBD and large international consortia datasets for eight psychiatric disorders, we conducted global genetic correlation analysis to quantify overall genetic overlap, local genetic correlation analysis to identify region-specific associations, summary data-based Mendelian randomization (SMR) to evaluate putative causal gene-trait relationships, and multi-trait analysis of GWAS (MTAG) to detect pleiotropic variants. RESULTS: Significant global genetic correlations were observed between IBD and ADHD (rho = 4.79 × 10, p = 3.07 × 10), anxiety disorder (rho = 1.89 × 10, p = 8.02 × 10), ASD (rho = 6.65 × 10, p = 7.24 × 10), OCD (rho = 7.84 × 10, p = 1.32 × 10), and PTSD (rho = 2.19 × 10, p = 1.16 × 10). Local genetic correlation analysis identified 274 significant regions (Bonferroni-corrected), with loci 464 (chr3: 47.6-50.4 Mb) and 960 (chr6: 31.3-31.4 Mb) showing consistent cross-trait associations. MTAG identified 1,125 independent pleiotropic loci, while SMR and MAGMA integration prioritized 21 key pleiotropic genes, including NOD2, IL10, and AURKB. Enrichment analyses highlighted immune-related and neurobiological pathways, including JAK-STAT signaling, FoxO signaling, oxidative stress response, and GABAergic synapse pathways. CONCLUSION: Our findings provide multi-layered genetic evidence supporting a structured and locus-specific shared genetic architecture between IBD and several psychiatric disorders. The identification of key genes and pathways, particularly NOD2 and immune-synaptic signaling cascades, offers potential molecular targets for understanding and managing comorbid disease within the GBA framework.
Electroconvulsive therapy in Germany: a nationwide multilevel analysis of determinants, regional patterns, and institutional variation.
Dreger M, Uphaus A, Zilles-Wegner D … +3 more , Sartorius A, Guhra M, Kreisel S
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42362820 · Publisher ↗
Electroconvulsive therapy (ECT) is an effective treatment for severe psychiatric disorders, yet its use may be shaped not only by clinical need but also by structural and institutional factors. Using nationwide 2023 admi...
Electroconvulsive therapy (ECT) is an effective treatment for severe psychiatric disorders, yet its use may be shaped not only by clinical need but also by structural and institutional factors. Using nationwide 2023 administrative data from the German psychiatric prospective payment system (PEPP), we examined whether regional ECT utilization corresponded to regional diagnostic burden and assessed patient-, institutional-, and regional-level factors associated with receiving ECT. The analysis included 837,762 inpatient psychiatric discharges; in addition, descriptive information on day hospital ECT activity was obtained from publicly available aggregate data. Across inpatient and day hospital settings, 16,312 cases received ECT and 72,193 ECT procedures were documented. Regional ECT rates showed essentially no association with the regional frequency of ECT-relevant diagnoses. ECT provision was also strongly concentrated in larger institutions. In multilevel models, depression, catatonia, schizophrenia-spectrum disorders, bipolar disorder, female sex, older age, and annual psychiatric case volume were positively associated with ECT receipt. However, substantial residual heterogeneity remained at the institutional level (median odds ratio 23.6) after adjustment for case mix and contextual factors. These findings suggest that variation in ECT use in Germany is only weakly aligned with proxies of clinical need and is shaped to a considerable extent by institutional and structural conditions, indicating potential inequities in access to ECT across regions and providers.
Neuropathophysiological changes associated with mirtazapine treatment response in major depressive disorder: insights into bottom-up dopaminergic pathways and prefrontal control networks.
Lee Y, Simulionyte E, Hebib S … +7 more , Manook A, Picotin R, Jooyandeh SM, Baghai TC, Schwarzbach J, Rupprecht R, Gruber O
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42362819 · Publisher ↗
Major depressive disorder (MDD) shows striking heterogeneity in both symptoms and underlying pathophysiology, and the absence of biologically grounded subtypes often results in a prolonged trial-and-error process when se...
Major depressive disorder (MDD) shows striking heterogeneity in both symptoms and underlying pathophysiology, and the absence of biologically grounded subtypes often results in a prolonged trial-and-error process when selecting effective treatments. This has motivated efforts to identify biomarkers that may predict individual treatment responses. Although mirtazapine is widely used and its efficacy is well established in clinical settings, neuroscientific studies on its treatment response remain limited relative to other antidepressants. To address this gap, this study examined pre-treatment pathophysiological neural features associated with subsequent response to mirtazapine. Sixty-seven individuals with MDD underwent functional magnetic resonance imaging during a conditioned reward task and then received monotherapy with mirtazapine or one of two comparator antidepressants (agomelatine or a selective serotonin reuptake inhibitor). Mirtazapine responders demonstrated increased pre-treatment activation in core components of the mesolimbic dopaminergic pathway, particularly the ventral tegmental area and ventral striatum, as well as in prefrontal and functionally connected regions implicated in reward evaluation, reward-related behavioral inhibition, and reward-based decision-making. Importantly, many of these response-related activations were specific to the mirtazapine group. These findings suggest that altered engagement of mesolimbic dopaminergic pathways and prefrontal regulatory networks during reward processing may characterize an MDD subtype responsive to mirtazapine, and that such patterns may serve as biomarkers for identifying patients likely to benefit from this treatment.
Differential associations of childhood trauma subtypes with clinical symptoms, cognitive function, suicidal intent, and age at onset in Chinese patients with chronic schizophrenia.
Wang H, Ran S, Lu D … +2 more , Li Z, Zhang X
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42362818 · Publisher ↗
BACKGROUND: Childhood trauma has been linked to adverse clinical features in schizophrenia, but whether these associations differ by trauma subtype remains unclear. This study examined the differential associations of tr...
BACKGROUND: Childhood trauma has been linked to adverse clinical features in schizophrenia, but whether these associations differ by trauma subtype remains unclear. This study examined the differential associations of trauma subtypes with multiple clinical features in Chinese patients with chronic schizophrenia. METHODS: This multicenter cross-sectional study included 649 patients with chronic schizophrenia recruited from ten psychiatric hospitals in China. Childhood trauma, psychotic symptoms, cognitive function, insomnia, depressive symptoms, and suicidal intent were assessed using the CTQ-SF, PANSS, RBANS, ISI, HAMD-24, and BSSI, respectively. Partial correlation analyses and stepwise multivariable linear regression models were performed. RESULTS: Emotional abuse was significantly associated with positive symptoms (B: 0.231, 95% CI: 0.044, 0.418), insomnia severity (B: 0.259, 95% CI: 0.138, 0.379), depressive symptoms (B: 0.362, 95% CI: 0.169, 0.556), suicidal intent (B: 0.543, 95% CI: 0.286, 0.800), and earlier age at onset (B: -0.335, 95% CI: -0.540, -0.131). Sexual abuse was significantly associated with poorer language performance (B: -0.689, 95% CI: -1.276, -0.102) and greater depressive symptom severity (B: 0.330, 95% CI: 0.039, 0.622). No trauma subtype was significantly associated with negative symptoms, general psychopathology, PANSS total score, immediate memory, visuospatial/constructional ability, attention, delayed memory, or RBANS total score. CONCLUSION: Emotional abuse showed the broadest pattern of associations across symptom domains, whereas sexual abuse was linked only to language performance and depressive symptoms. These findings highlight the potential value of assessing childhood trauma subtypes in schizophrenia, but should be interpreted cautiously given the cross-sectional design and retrospective trauma assessment.
The prevalence of insomnia disorder in inpatient psychiatric care.
Hertenstein E, Danker-Hopfe H, Mikutta C … +19 more , Allenbach E, Schmidt P, Spath M, Großkurth E, Schneider CL, Frase L, Schilling C, Schredl M, Anzenberger E, Göder R, Weber S, Norra C, Sander C, Mauche N, Makiol C, Strauß M, Wetter TC, Weber FC, Nissen C
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42362817 · Publisher ↗
Sleep and mental health are intricately linked. Insomnia - defined as a dissatisfaction with sleep quantity or quality - is highly prevalent among patients with psychiatric disorders, exerting a negative impact on treatm...
Sleep and mental health are intricately linked. Insomnia - defined as a dissatisfaction with sleep quantity or quality - is highly prevalent among patients with psychiatric disorders, exerting a negative impact on treatment outcome. However, the prevalence of insomnia on a symptom and diagnosis level (insomnia disorder) has not systematically been assessed in inpatient psychiatric care. The aim of this study was to systematically investigate the prevalence of insomnia symptoms and insomnia disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria in inpatient psychiatric care. Comprehensive diagnostic interviews were conducted by trained clinicians in four German and two Swiss psychiatric hospitals. A total of 427 inpatients with psychiatric disorders across diagnostic groups were included (225 female, 200 male, 2 non-binary, mean age 40.8 ± 15.1 years, mean duration of psychiatric illness 8.6 ± 10.6 years). The prevalence of comorbid insomnia disorder, according to DSM-5 criteria, was 30.4% (95% CI [26.0%; 34.8%]). Additionally, 38.4% of patients (95% CI [33.8%; 43.0%]) reported regular insomnia symptoms but did not fulfill disorder criteria. Together, 68.8% of the sample (95% CI [66.4%; 73.2%]) were regularly affected by insomnia complaints. The prevalence of insomnia disorder was independent of age and diagnostic group, but significantly higher in women than in men (Fisher's exact test: p = 0.006, OR = 1.8, 95% CI [1.2; 2.8]). The current study is, to our knowledge, the first interview-based systematic investigation of the prevalence of insomnia disorder in inpatient psychiatric care. The high prevalence of around one third of patients is a call for action to implement a systematic diagnostic evaluation and state-of-the-art treatment of insomnia in routine psychiatric care. Of note, recent work demonstrates that adaptations of cognitive behavioral therapy for insomnia (CBT-I) - the first-line treatment according to guidelines-are feasible in inpatient psychiatric care. These interventions might have the potential to reduce the overprescription of hypnotic medication and to improve sleep and health.
Mechanisms of weight gain associated with valproic acid: a scoping review.
Popkova D, Fellendorf F, Vinberg M … +8 more , Ceylan D, Bukova-Zideluna A, Fleischmann E, Dalkner N, Tmava-Berisha A, Lenger M, Manchia M, Reininghaus E
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42334569 · Publisher ↗
INTRODUCTION: Valproic acid (VPA), a widely prescribed mood stabilizer and antiepileptic drug, is frequently associated with metabolic side effects, particularly weight gain. Despite its clinical relevance, the range and...
INTRODUCTION: Valproic acid (VPA), a widely prescribed mood stabilizer and antiepileptic drug, is frequently associated with metabolic side effects, particularly weight gain. Despite its clinical relevance, the range and diversity of mechanisms underlying VPA-associated weight gain remain incompletely mapped. OBJECTIVES: To map the breadth of evidence on mechanisms of VPA-associated weight gain, characterize the types of studies and populations investigated, and identify knowledge gaps to inform future research. METHODS: This PRISMA-ScR-guided scoping review searched PubMed, Cochrane Library, Scopus, and Google Scholar for studies on VPA-weight gain mechanisms in adults. One reviewer charted data using a piloted form; two independently assessed quality (Newcastle-Ottawa Scale). Sources were grouped by mechanistic pathway with descriptive summaries and vote-counting. RESULTS: Fifteen studies (n = 1,339 participants) were included, representing diverse designs: cross-sectional (n = 4), prospective observational (n = 3), genetic association (n = 2), and others. Evidence mapped to three primary mechanistic domains: hormonal dysregulation (like elevated insulin, leptin, insulin resistance, and other findings); genetic predispositions, including CYP2C19 polymorphisms, CRTC1 methylation, and other genetic variants; and lipid metabolism alterations (increased TC, LDL-C, TG, FFAs; decreased Apo A1; mixed HDL-C findings). Hormonal and lipid pathways are well-documented, while genetic mechanisms require validation in larger, standardized cohorts. CONCLUSIONS: This scoping review identifies a heterogeneous evidence base with well-established hormonal and lipid mechanisms and emerging genetic pathways. Key gaps include underrepresentation of bipolar disorder populations, limited longitudinal genetic studies, and lack of integrated frameworks combining hormonal, genetic, and metabolic data. Findings inform future research priorities and highlight the need for personalized monitoring strategies.
Dissociative experiences and self-reported interoceptive traits in maladaptive daydreamers: a network analysis.
Bufalari I, Abergel L, Zagaria A … +3 more , Fusar-Poli L, Ferreri L, Sperduti M
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42334568 · Publisher ↗
Maladaptive Daydreaming (MD) is a proposed mental health condition characterized by compulsive, immersive daydreaming that interferes with daily functioning. Although MD is strongly associated with dissociative experienc...
Maladaptive Daydreaming (MD) is a proposed mental health condition characterized by compulsive, immersive daydreaming that interferes with daily functioning. Although MD is strongly associated with dissociative experiences, its relation to interoception remains unexplored. In this study, we investigated dissociative symptoms and self-reported interoception in individuals with MD compared to matched controls. A total of 137 Italian-speaking participants (83 MDers and 54 controls) completed an online survey assessing maladaptive daydreaming (MDS-16), dissociation (DES-II), and interoception (MAIA-2). As expected, MDers showed significantly higher levels of dissociation - particularly in the domains of absorption/imagination and depersonalization/derealization - compared to controls. Moreover, MDers exhibited lower scores on specific interoceptive subscales: Attention Regulation, Body Listening, and Trusting. Network analyses highlighted maladaptive daydreaming as a central node linking dissociation and interoception. These findings suggest that individuals with MD may experience altered interoception and that maladaptive daydreaming might function as an escape from unpleasant bodily states. This is the first study to document altered interoception in MD, future research could extend the findings by incorporating objective measures. Clinically, the results highlight the potential utility of interventions aimed at improving interoception - such as mindfulness-based approaches - in addressing maladaptive daydreaming and its dissociative correlates.
Distinct effects of current suicidal symptoms and lifetime suicide attempts on C-reactive protein levels and executive function in young people with major affective disorders.
Hsu JW, Chen LC, Bai YM … +2 more , Tsai SJ, Chen MH
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42329322 · Publisher ↗
BACKGROUND: This study addresses the complex associations between current suicidal symptoms, lifetime suicide attempt history, C-reactive protein (CRP) levels, and executive dysfunction among young people with major affe...
BACKGROUND: This study addresses the complex associations between current suicidal symptoms, lifetime suicide attempt history, C-reactive protein (CRP) levels, and executive dysfunction among young people with major affective disorders. METHODS: A total of 171 young people with major affective disorders presenting varying levels of suicidal symptoms and 97 healthy young people aged 12 to 24 years were recruited for this study. Current suicidal symptom severity was classified as none, mild, or strong if an individual has scores of 0, 2-3, and ≥ 4, respectively, on item 10 of the Montgomery-Åsberg Depression Rating Scale (MADRS). The presence of a lifetime history of suicide attempts was also determined. All participants had CRP levels measured and underwent the Wisconsin Card Sorting Test (WCST). RESULTS: Generalized linear models (GLM) with adjustments for demographic characteristics, diagnoses, and non-suicidal depressive symptoms indicated that patients presenting strong suicidal symptoms had the highest CRP levels (p = 0.004) and percentage of nonperseverative errors on the WCST (p = 0.002), whereas those with mild suicidal symptoms were more likely to have intermediate CRP levels relative to non-suicidal young people. Only young people with a history of suicide attempts exhibited an increased percentage of perseverative errors on the WCST (p = 0.023) compared with the healthy controls. DISCUSSION: Our findings suggest that CRP levels and the percentage of nonperseverative errors on the WCST served as concurrent markers of suicidality, whereas the percentage of perseverative errors served as a trait marker of suicidality among young people with major affective disorders.
Clozapine-associated pneumonia: a gut-lung-brain axis perspective.
Cai Y, Nakamura H, Takeuchi H … +1 more , Hashimoto K
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42329321 · Publisher ↗
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