European Archives Of Psychiatry And Clinical Neuroscience[JOURNAL]
Sun
200 papers
Alexithymia in Chinese methamphetamine dependent males: prevalence, demographic, clinical correlates, and relationship with craving.
Kiyani ART, Zhang XY, Bashir M … +2 more , Ullah S, Wang DM
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41591484 · Publisher ↗
BACKGROUND AND OBJECTIVES: Alexithymia is a state of complex personality trait, where individuals are characterized by a predicament in recognizing and expressing emotions, which are mainly caused by genetic, neurologica...
BACKGROUND AND OBJECTIVES: Alexithymia is a state of complex personality trait, where individuals are characterized by a predicament in recognizing and expressing emotions, which are mainly caused by genetic, neurological, or psychological factors. In this study, it was hypothesized that methamphetamine (MA) dependent males having alexithymia are susceptible to utilizing MA at a frequent or enhanced rate. Moreover, the study aimed to quantify the prevalence of alexithymia in 411 Chinese MA-dependent males based on variables related to demographic characteristics and drug use. METHODS: Self-reported questionnaires were utilized to gather the demographic data from the 411 selected patients in Xinhua Drug Rehabilitation Center, China. The Toronto Alexithymia Scale-20 (TAS-20) was employed to evaluate the level of alexithymia within the MA-dependent males. The effect of craving was assessed by using the Obsessive Compulsive Drug Use Scale (OCDUS). RESULTS: Results and Discussions: The prevalence rate of alexithymia found in MA-dependent males was 30.41% evaluated using the relationship. i.e. (Alexithymia Patients / Total No. of Sample). Note that the scores of craving frequency, drug interference, drug control, and OCDUS were significantly higher in alexithymic compared to non-alexithymic MA-dependent males. Pearson’s correlation indicated a positive association between various dimensions of alexithymia and measures of drug craving, where OCDUS was observed to be positively correlated with TAS-20 and its sub-scales. Eventually, the logistic regression analysis found that craving frequency and drug interference played a significant positive role in predicting alexithymia within MA-dependent males. CONCLUSION: Our findings exhibit a significantly higher prevalence of alexithymia in Chinese MA-dependent males, which is found to be strongly associated with variables related to drug use. In addition, drug interference and craving frequency are recognized.
Neuroactive steroids for the treatment of depression and anxiety: gaps and promises.
Rupprecht R, Schüle C, Gudermann T
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41579166 · Full text
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Genetic evidence on chemical communication between gut microbiota and neurological and psychiatric disorders: a Mendelian randomization study.
Yu S, Ye Z, Zhao W … +7 more , Yu X, Qiu Y, Lin K, Lu T, Ge L, Sun J, Hua R
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41575555 · Publisher ↗
BACKGROUND: Accumulating evidence from clinical trials and preclinical studies revealed the importance of the microbiota-gut-brain axis (MGBA) in neurological and psychiatric disorders (NPDs). MGBA remains a blueprint fo...
BACKGROUND: Accumulating evidence from clinical trials and preclinical studies revealed the importance of the microbiota-gut-brain axis (MGBA) in neurological and psychiatric disorders (NPDs). MGBA remains a blueprint for extended explorations. METHODS: We examine the bidirectional association between 5 NPDs (late-onset Alzheimer’s disease (AD), migraine, autism spectrum disorder (ASD), all anxiety disorder, depression) and gut microbiota (GM) via microbial-derived metabolites, neurotransmitter, and precursors including total branched-chain amino acids (BCAA), isoleucine, leucine, valine, acetate, tryptophan, kynurenine, glutamate, tyrosine, serotonin using two step Mendelian randomization. Five methods were performed, including inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. The robustness of results was supported by Cochran’s Q test, the MR-Egger regression, the MR pleiotropy residual sum and outlier, and the leave-one-out method. RESULTS: After false discovery rate correction, we found elevated isoleucine in plasma as a risk factor for AD and elevated tyrosine in plasma as a risk factor for anxiety. Conversely, AD has genetically effect on a lower level of total BCAA, isoleucine, leucine, valine, glutamate, and tyrosine in plasma. We also found that Clostridia, Clostridiales, Sutterella, and Ruminococcus torques group were positively correlated with isoleucine. Elevated Sutterella abundance was found strongly positively correlated with ASD. Desulfovibrionales and Desulfovibrionaceae were found strongly positively correlated with AD. Pathways of Clostridia/Clostridiales/Ruminococcus torques group/Sutterella- isoleucine- AD were established with mediating percentages ranging from − 54.265% to 132.908%. CONCLUSION: Our study elucidates how chemical signalling bridges communication between GM and NPDs, paving avenues for microbiota-based treatment.
Episodic memory deficits and processes in post-COVID condition.
Oliver-Mas S, Matias-Guiu JA, Delgado-Alonso C … +8 more , Valles-Salgado M, Gil-Moreno MJ, López-Carbonero JI, Fernández-Romero L, Cuevas C, Delgado-Álvarez A, Matias-Guiu J, Diez-Cirarda M
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41563438 · Full text
Cognitive dysfunction is one of the most prevalent symptoms in patients with post-COVID condition (PCC) and episodic memory has been highlighted as one of the most impaired cognitive domains in these patients. However, f...
Cognitive dysfunction is one of the most prevalent symptoms in patients with post-COVID condition (PCC) and episodic memory has been highlighted as one of the most impaired cognitive domains in these patients. However, few studies have specifically assessed episodic memory processes in these patients. This study aims to comprehensively investigate the memory function in patients with PCC. We conducted a cross-sectional study involving 157 patients with PCC and 74 healthy controls. Participants underwent a comprehensive neuropsychological assessment and memory assessment, including the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), the Free and Cued Selective Reminding test (FCSRT), the Open-Trial Selective Reminding Test (OT-SRT), and a Mental Ability Questionnaire (FLEI). We compared groups and evaluated the correlation between episodic memory and neuropsychological and clinical assessments. Patients with PCC showed reduced performance on the LASSI-L, the FCSRT and the OT-SRT compared to controls. The memory scores showed positive moderate correlations with attention tests and positive low correlations with language, visuospatial or executive functions. Subjective memory complaints were related to poorer memory performance. LASSI-L was the test most associated with subjective memory complaints, whereas OT-SRT was the test less influenced by attention tests. The study found multiple memory processes impaired in patients with PCC, specifically in initial encoding, learning information acquisition and storage, and in retrieval, with only partial improvement with cues and recognition, and with significant susceptibility to the effects of retroactive semantic interference. These findings are relevant for characterising the cognitive deficits of patients with PCC and for designing interventional strategies.
Disrupted brain network dynamics and cognitive dysfunction in drug-naive major depressive disorder: an EEG microstate study.
Bao C, Zhang Q, Hu S … +6 more , Zou H, Chen W, Xia Y, Yan R, Yao Z, Lu Q
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41563437 · Publisher ↗
Dysfunctions in brain network dynamics have been linked to emotional disorders. However, there is limited research exploring the connection between resting-state EEG brain networks and cognitive functions in individuals...
Dysfunctions in brain network dynamics have been linked to emotional disorders. However, there is limited research exploring the connection between resting-state EEG brain networks and cognitive functions in individuals with Major Depressive Disorder (MDD). The objective of this study is to examine irregular brain network activity and its relationship with cognitive performance, utilizing EEG microstates, in order to shed light on the underlying neuropathological mechanisms of MDD. This study included 68 drug-naïve MDD individuals and 50 healthy control participants (HCs). Demographic data were collected, and cognitive function assessments were performed. Concurrently, resting-state brain activity was captured using a 64-channel EEG. Additionally, Pearson correlation analysis was used to explored the relationship between these factors in MDD patients. We identified four distinct EEG microstate topographic maps. In comparison with the healthy control group, the coverage, duration, and occurrence of microstates A and D were significantly diminished, whereas those of microstate B were markedly increased. The performance on various neurocognitive tests (Trail Making Test [TMT], Symbol Digit Modalities Test [SDMT], Stroop Color-Word Test [SCWT]) for the MDD group was consistently lower than that of the HCs. In the MDD patients, all parameters of microstate A exhibited a negative correlation with Stroop's color-naming and word-color time, while the coverage and duration of microstate D correlated positively with scores on the SDMT. Our study indicated that individuals with MDD display aberrant microstate dynamics, and these results corroborate the link between alterations in microstate activity and cognitive function in MDD patients.
Brain oscillation-synchronized stimulation for major depression: a randomized controlled trial comparing EEG-triggered repetitive TMS with standard iTBS (Acronym: BOSSFRONT2).
Lieb A, Zrenner B, Becker-Sadzio J … +6 more , Gordon PC, Kozák G, Zrenner C, Martus P, Ziemann U, Fallgatter A
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41563436 · Full text
BACKGROUND: Major depressive disorder (MDD) is a common severe mental disorder with enormous socioeconomic costs for the patient and society alike. Current pharmacological and psychotherapeutic treatments are ineffective...
BACKGROUND: Major depressive disorder (MDD) is a common severe mental disorder with enormous socioeconomic costs for the patient and society alike. Current pharmacological and psychotherapeutic treatments are ineffective in a substantial fraction of patients and can be accompanied by unwanted side effects. METHODS: Using a novel non-invasive brain stimulation method to specifically target and modulate dysfunctional brain oscillations with high spatial and temporal precision this study will investigate the efficacy of EEG-triggered transcranial magnetic stimulation (TMS) to alleviate depressive symptoms in 28 patients with MDD in a 1:1-randomized, double blind, standard treatment-controlled pilot trial. In the experimental condition, stimulation will be brain oscillation-synchronized based on the EEG-extracted endogenous theta oscillation over left dorsomedial prefrontal cortex (DMPFC). The control condition will consist of standard TMS therapy following an FDA-approved intermittent theta-burst stimulation (iTBS) protocol over left dorsolateral prefrontal cortex (DLPFC). The treatment will be performed over four consecutive weeks (20 sessions) and the primary outcome will be the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) after the last versus before the first treatment session. DISCUSSION: The aim of the study is to gain exploratory evidence for the feasibility and efficacy of EEG-synchronized TBS of left DMPFC compared to a standard FDA-approved treatment (iTBS of left DLPFC) in a double-blind randomized parallel-design pilot clinical trial. Positive results will pave the way for a larger RCT to prove the superiority of personalized, brain oscillation-synchronized non-invasive brain stimulation therapies as novel, effective and well-tolerated treatment in MDD. TRIAL REGISTRATION: Trial Registration: NCT06345651, date of registration: 2024-01-08, https://clinicaltrials.gov/study/NCT06345651 The trial is conducted in accord with protocol version number 2022-09, Version 3. Recruitment started in January 2024, and recruitment is ongoing. The recruitment phase is projected to conclude by December 2026.
Problem-, resources- and goals-oriented (PRoGO) approach in psychiatry: illustrated by the case of Ludwig II of Bavaria.
Leucht S, Davis JM, Böge K … +3 more , ElDeeb A, Strube W, Förstl H
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41563435 · Full text
Mental health issues are dimensional in nature, yet both ICD-11 and DSM-5 are categorical classifications, leaving many patients not fitting into them. Using Bavaria’s “fairy-tale” king Ludwig II—whose diagnosis remains...
Mental health issues are dimensional in nature, yet both ICD-11 and DSM-5 are categorical classifications, leaving many patients not fitting into them. Using Bavaria’s “fairy-tale” king Ludwig II—whose diagnosis remains debated—as an example, we illustrate how the Problem-, Resources-, and Goal-Oriented (PRoGO) approach can lead to a better characterisation of patients and guide personalized treatment planning.
Alteration of brain activity in adolescent bipolar disorder: impact of positive emotional stimuli on attentional process.
Shen L, Wang L, Wang X … +8 more , Wu F, Zhang J, Wu H, Grecucci A, Xiao Q, Liu X, Yi X, Chen BT
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41518544 · Publisher ↗
BACKGROUND: There is limited literature on emotional regulation and cognitive control in adolescent patients with bipolar disorder (BD) in response to positive emotional stimuli. Few brain functional magnetic resonance i...
BACKGROUND: There is limited literature on emotional regulation and cognitive control in adolescent patients with bipolar disorder (BD) in response to positive emotional stimuli. Few brain functional magnetic resonance imaging (fMRI) studies have employed emotion-based Go/No-Go tasks to examine neural process underlying BD. This study aimed to investigate alterations of brain activity on fMRI during positive emotional stimuli (i.e., happy faces) and its impact on attentional processing in adolescent patients with BD. METHOD: This study enrolled 43 adolescents diagnosed with BD and 18 age- and gender-matched healthy controls. All participants underwent structured interviews, questionnaire/scale assessment for BD symptoms, and task-based brain fMRI with an emotional Go/No-Go paradigm. Clinical data and neural activity in response to neutral and positive emotional stimuli were compared between the groups. RESULTS: Compared to the healthy controls, the patients with BD showed significantly increased activity in key regions within the cognitive control network, the default mode network, and the limbic system under the “happy-Go minus neutral-Go” condition during the brain fMRI. Notably, hyperactivation in the left dorsolateral superior frontal gyrus, left opercular part of the inferior frontal gyrus, left inferior parietal lobule, and left thalamus was significantly correlated with the emotional Go omission rate. CONCLUSION: This study showed alteration of brain activity in specific brain regions for attentional control and emotional regulation in adolescents with BD during positive emotional stimuli. The results of this study enhance our understanding of neurobiological mechanisms underlying adolescent BD and implicate potential treatment strategies focusing on attentional training and emotional management.
Evaluating causal links between retinal thickness, Alzheimer's disease, and circulating total-tau: evidence from Mendelian randomization and colocalization analysis.
Sheng D, Wang S, Xiao Z … +3 more , Liu W, Xiao B, Zhou L
Eur Arch Psychiatry Clin Neurosci · 2026 Jan · PMID 41518543 · Publisher ↗
BACKGROUND: Observational studies have reported associations between retinal thickness and Alzheimer’s disease (AD); however, the causal relationship remains uncertain. OBJECTIVE: To investigate the potential causal rela...
BACKGROUND: Observational studies have reported associations between retinal thickness and Alzheimer’s disease (AD); however, the causal relationship remains uncertain. OBJECTIVE: To investigate the potential causal relationships between retinal thickness and AD, and circulating total-tau levels using Mendelian randomization (MR) and genetic colocalization analyses. METHODS: Summary-level data of genome-wide association studies on retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness, AD and circulating total-tau levels were utilized for causal analysis. The inverse-variance weighted (IVW) method served as the primary analytical approach, supplemented by MR-Egger, robust adjusted profile score, maximum likelihood, and weighted median methods. Sensitivity analyses were conducted to ensure robustness. Genetic colocalization analysis was utilized to identify potential shared causal variants. RESULTS: The IVW estimates from the discovery MR analysis indicated no statistically significant causal effect of genetically predicted RNFL or GC-IPL thickness on AD or circulating total-tau levels, and exploratory reverse MR analysis found no causal link either (PIVW > 0.05). Replication bidirectional MR analysis produced consistent negative results (PIVW > 0.05). Sensitivity analyses demonstrated robustness across all MR methods. Genetic colocalization analysis identified no shared causal variants between RNFL or GC-IPL thickness and AD or circulating total-tau (posterior probability H4 < 0.75). Post-hoc power analysis revealed severely limited statistical power for forward MR analyses. CONCLUSION: Our study found no statistically significant genetic causal associations between retinal thickness, AD, and total-tau levels. However, severely limited statistical power precludes definitive exclusion of small causal effects. Future studies with substantially larger sample sizes are needed to achieve adequate statistical power for definitive conclusions. Since all GWAS datasets were restricted to European ancestry, caution is required when generalizing these findings, and replication in diverse populations is encouraged.
Choroid plexus alterations in long COVID and their associations with IL-6.
Cao Y, Lizano P, Garza AP … +7 more , Dunay IR, Zhou X, Reuken PA, Stallmach A, Walter M, Li M, Besteher B
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41498966 · Publisher ↗
SARS-CoV-2 disrupts the choroid plexus (ChP) epithelium by binding to the ACE-2 receptor, causing blood cerebrospinal fluid barrier leakage and permitting interleukin (IL)-6 and pathogens into the brain, subsequently lea...
SARS-CoV-2 disrupts the choroid plexus (ChP) epithelium by binding to the ACE-2 receptor, causing blood cerebrospinal fluid barrier leakage and permitting interleukin (IL)-6 and pathogens into the brain, subsequently leading to demyelination, white matter (WM) damage in long COVID, and clinical worsening. The role of the ChP in long COVID and its relationships to WM integrity, IL-6, clinical symptoms, and ACEIs/ARBs medications remains unclear. Fifty-two long COVID individuals, 21 COVID-19 survivors, and 26 healthy controls (HCs) completed Montgomery-Asberg Depression Rating Scale (MADRS), Montreal Cognitive Assessment (MoCA) and interleukin (IL) -6 assessments. Manually segmented ChP volume and global free water corrected WM integrity was compared among groups, and consideration of ACE inhibition on the ChP was examined. Partial correlations explored relationships among ChP volume, IL-6, fractional anisotropy tissue (FAt), and symptoms. ChP changes were also assessed at baseline and after one year. Long COVID individuals showed higher MADRS (p < 0.001), lower MOCA score (p < 0.001), and smaller ChP volume (p = 0.02) among groups. Larger ChP volume was significantly correlated to higher IL-6 levels (r = 0.478, p = 0.005) in long COVID. No ChP volume differences were found over time in the long COVID group or HCs that transitioned to COVID-19 survivors. COVID-19 survivors had larger ChP volume at follow-up compared to baseline (p = 0.04). The smaller ChP in long COVID seems to involve persistent but low-grade blood-CSF barrier dysfunction and epithelial stress. IL-6 levels may affect ChP permeability and suggest ongoing neuroinflammation in the long COVID group.
Sex-specific global, regional and national burden of dysthymia and major depression disorder in older adults from 1990 to 2021: a systematic analysis of the global burden of disease 2021 study.
Yuan X, He Y, Cao Q … +7 more , Hu Y, Li X, Ran Z, Li Y, He J, Yan C, Xiong J
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41498965 · Publisher ↗
Dysthymia and major depression disorder impair the wellbeing of older adults, their families, and communities. Understanding its global disease burden and trends in older adults over 60 is fundamental for policy making....
Dysthymia and major depression disorder impair the wellbeing of older adults, their families, and communities. Understanding its global disease burden and trends in older adults over 60 is fundamental for policy making. Therefore, we obtained data from Global Burden of Diseases Study 2021 in 204 countries and territories from 1990 to 2021. We calculated the age-standardized prevalence, incidence, disability-adjusted life years (DALYs) rates, and estimated annual percentage change by age, sex, and socio-demographic index (SDI) to assess burden and quantify the temporal trends. We then used spearman correlation analysis to examine the relationship between age-standardized rates and SDI, and adopted a Bayesian age-period-cohort model to predict trends to 2030. In 2021, there were over 67.6 million cases of dysthymia and major depression disorder in older adults globally, with an age-standardized prevalence rate of 6203.2 per 100,000 (95% Uncertainty Interval: 5128.4-7464.5). Age-standardized prevalence, incidence, and DALY rates increased in high-income Asia Pacific and East Asia. Disease burden negatively correlated with SDI levels. A heavier burden was observed in older females consistently across all regions and age groups. Disease burden in older adults peaked at age 60-64 and declined with aging in most but low SDI regions, where an increasement preceded the decline. By 2030, the age-standardized prevalence, incidence, and DALY rates are predicted to increase globally, with a higher projected burden in older females. In conclusion, the allocation of health resources should focus on addressing regional disparities, with special attention to vulnerable groups such as older females in economically disadvantaged regions.
Suicide risk and malpractice considerations in geriatric care.
Sher L
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41498964 · Publisher ↗
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Dopamine synthesis capacity in patients with remitted psychosis: correlates and one year outcome on relapse.
Hui CLM, Wong CCL, Yang NCL … +18 more , Choi EMH, Hui PWM, Lui ECY, Tao JT, Ho ECN, Suen YN, Chen S, Leung EYL, Ho GCL, Lo GG, Chan CWH, Yeung WS, Poon LT, Lui SSY, Lee EHM, Chan SKW, Chang WC, Chen EYH
Eur Arch Psychiatry Clin Neurosci · 2026 Jan · PMID 41493461 · Publisher ↗
BACKGROUND: Biological predictors of relapse in psychosis remain underexplored. We examined whether dopamine synthesis capacity (DSC) predicts psychotic relapse one year after remission, and its associations with baselin...
BACKGROUND: Biological predictors of relapse in psychosis remain underexplored. We examined whether dopamine synthesis capacity (DSC) predicts psychotic relapse one year after remission, and its associations with baseline clinical and cognitive factors. STUDY RESIGN: In a prospective one-year follow-up study, forty-seven patients with remitted psychosis and fifteen age- and sex-matched healthy controls underwent positron emission tomography/computed tomography (PET/CT) scanning at baseline, with DSC indexed by mean standardized uptake value ratios (SUVr). Relapse was assessed monthly over one year. STUDY RESULTS: SUVr measures did not differ between patients and controls. Within patients, a higher putamen-to-cerebellum SUVr ratio at baseline was associated with male sex (p = 0.019), unmarried status (p = 0.044), more premorbid schizoid-schizotypal traits (p = 0.015), and greater general psychopathology (p = 0.010); only the latter remained significant after correction for multiple comparisons. Higher caudate-to-cerebellum SUVr was also linked to schizoid-schizotypal traits (p = 0.007), while higher putamen-to-caudate SUVr correlated with better insight (p = 0.017). At one year, relapsers showed lower putamen-to-caudate SUVr (p < 0.001), were more often immigrants (p = 0.002), had poorer insight into antipsychotic benefits (p = 0.003), and were more likely to have discontinued medication at baseline (p = 0.029). Penalized logistic regressions confirmed that lower baseline putamen-to-caudate SUVr predicted relapse independently of medication status at both baseline (p = 0.037) and follow-up (p = 0.044). CONCLUSIONS: Baseline reductions in striatal DSC predicted relapse regardless of medication, supporting its role as a marker of dopaminergic vulnerability.
Phase synchronization alterations of EEG oscillations during emotional video processing in depression and anxiety: a transdiagnostic study.
Sun J, Niu Z, Liu L … +7 more , Gao T, Xing M, Xu H, Peng H, Zhao Q, Wang J, Yu X
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41491028 · Publisher ↗
BACKGROUND: Emerging evidence indicates overlapping neurobiological variations across transdiagnostic psychiatric disorders. Considering depression and anxiety as the most common and co-occurring symptoms in affective di...
BACKGROUND: Emerging evidence indicates overlapping neurobiological variations across transdiagnostic psychiatric disorders. Considering depression and anxiety as the most common and co-occurring symptoms in affective disorders, we hypothesize shared symptom-related electrophysiological aberrations in the neural rhythmic oscillations across diagnostic boundaries. METHODS: 53 treatment-naïve patients with major depressive disorder, generalized anxiety disorder, or depressive episode in bipolar disorder, and 83 healthy controls (HC), underwent 64-channel electroencephalographic (EEG) recording while watching 10 min of neutral, sad, happy and fearful videos. The phase locking value (PLV) based on individual alpha peak frequency (iAPF) was used to measure phase synchronization alteration of EEG oscillations. RESULTS: Compared with HCs, patients exhibited widespread phase synchronization disturbances, characterized by prominent gamma PLV reductions and low-frequency (delta/theta/alpha) increases across frontal, central, and parietal-occipital regions. Depressive symptoms correlated with decreased beta PLV in the central region during happy stimuli, increased alpha PLV in the parieto-occipital lobe during sad stimuli, and increased theta PLV in the frontal and parietal lobes during fearful stimuli. Anxious symptoms correlated with decreased gamma PLV in the right frontal and parietal lobes during happy stimuli, increased alpha PLV in right frontal and parietal lobes, and increased gamma PLV in the frontal and parietal lobes during fearful stimuli. CONCLUSIONS: This study supports shared symptom-related aberrations in EEG phase synchronization patterns across transdiagnostic affective disorders, as well as the divergent neural characteristics between depression and anxiety. These findings may provide potential implications for probing and modulating symptom-targeted neural oscillational biomarkers across diagnoses.
Association between neuronal pentraxin 2, ADHD symptoms, and executive functioning in adults with ADHD: a case-control study.
Kaya S, Kocabaş R, Sağlıyan B … +3 more , Bayırlı Ö, Yorulmaz AE, Kandeğer A
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41489639 · Publisher ↗
BACKGROUND: Neuronal pentraxin 2 (NPTX2), a synaptic protein regulating AMPA receptors and glutamate homeostasis, has been suggested as a biomarker of synaptic integrity in neurodegenerative and psychiatric disorders. Th...
BACKGROUND: Neuronal pentraxin 2 (NPTX2), a synaptic protein regulating AMPA receptors and glutamate homeostasis, has been suggested as a biomarker of synaptic integrity in neurodegenerative and psychiatric disorders. This study investigated plasma NPTX2 levels in adults with ADHD and their associations with symptom severity and executive functioning. METHODS: In this cross-sectional case-control study, 79 medication- and comorbidity-free adults with ADHD and 70 matched typical controls were recruited. Participants underwent structured clinical interviews, standardized self-report scales on ADHD and comorbid anxiety/depression symptoms, and neurocognitive tests (Stroop, Wisconsin Card Sorting, Cancellation, Serial Digit Learning, Judgment of Line Orientation). Plasma NPTX2 levels were measured using ELISA. Between-group comparisons, correlation analyses, and multiple regressions adjusting for demographic and comorbid symptoms were conducted. RESULTS: Adults with ADHD showed significantly higher NPTX2 levels than controls, with a small effect size. Within the ADHD group, higher NPTX2 was negatively correlated with ADHD symptom severity, excessive mind wandering, and poorer performance on executive function tests (Stroop, Wisconsin Card Sorting, Cancellation). These correlations were not observed in controls. Regression analyses confirmed that the association between NPTX2 and ADHD symptoms remained significant after adjusting for age, gender, education, and anxiety/depression scores. CONCLUSION: Elevated NPTX2 levels in adults with ADHD and their negative associations with symptom severity and executive dysfunction may suggest a potential compensatory neuroprotective role. NPTX2 may serve as a non-invasive biomarker reflecting synaptic processes in ADHD. Longitudinal and interventional studies are needed to clarify its temporal dynamics and clinical utility.
Cell senescence-related pathogenic genes in sleep disorders: a multi-omics Mendelian randomization study.
Li J, Ding S, Zhang X … +2 more , Tang L, Jiang W
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41489638 · Full text
OBJECTIVES: Sleep disorders are multifactorial conditions influenced by genetic and environmental factors. However, the causal roles of specific cellular senescence-related genes in distinct sleep disorders subtypes rema...
OBJECTIVES: Sleep disorders are multifactorial conditions influenced by genetic and environmental factors. However, the causal roles of specific cellular senescence-related genes in distinct sleep disorders subtypes remain unclear. This study aimed to dissect these relationships by integrating multi-omics data to identify potential causal pathways in sleep apnea and insomnia. METHODS: We conducted a multi-stage Mendelian randomization (SMR) study. We first performed an exploratory SMR analysis integrating a comprehensive list of senescence-related genes with genome-wide association study (GWAS) data for a broad sleep disorders phenotype from the FinnGen consortium. To address phenotype heterogeneity, we then performed in-depth, phenotype-specific SMR analyses for sleep apnea and insomnia, integrating data across three molecular levels: DNA methylation (mQTL), gene expression (eQTL), and protein abundance (pQTL). Significant findings were validated using colocalization, HEIDI tests, replication cohorts, and two-sample MR sensitivity analyses. RESULTS: Our discovery analysis on broad sleep disorders phenotype identified several candidate genes. Subsequent phenotype-specific analyses revealed distinct genetic architectures. Genetically predicted lower CTSB expression was associated with a reduced risk of sleep apnea (OR = 0.943, 95% CI = 0.905-0.983, P = 0.006, FDR = 0.23) a finding potentially mediated by methylation at cg19746565. Furthermore, SIRT6 emerged as a shared risk factor. Genetically predicted higher SIRT6 expression was associated with an increased risk of both sleep apnea (OR = 1.279, 95% CI = 1.124-1.456, P = 0.0002, FDR = 0.06) and insomnia (OR = 1.573, 95% CI = 1.099-2.251, P = 0.013, FDR = 0.61), with its effect on insomnia being validated in brain hypothalamus tissue. CONCLUSIONS: Our multi-omics MR analysis has identified BLK, CTSB, TP53INP1, DNMT3A, ITPR1, and SLC16A7 as pivotal factors in the pathogenesis of sleep disorders. These findings provide a foundation for innovative early interventions and therapeutic strategies for sleep disorders.
Causal association between lipid profile and mental disorders: evidence from a bidirectional Mendelian randomization study.
Hu W, Wu Y, Li P
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41489637 · Publisher ↗
BACKGROUND: Observational studies have indicated interplay between lipid profiles and mental disorders, but genetic causal evidence remains limited. This study aimed to assess bidirectional causal links between lipid pro...
BACKGROUND: Observational studies have indicated interplay between lipid profiles and mental disorders, but genetic causal evidence remains limited. This study aimed to assess bidirectional causal links between lipid profiles and five major mental disorders using Mendelian randomization (MR) analysis. METHODS: We performed a bidirectional two-sample MR analysis utilizing genome-wide association study (GWAS) summary statistics from European populations. Genetic instruments were selected for five psychiatric disorders (major depressive disorder (MDD), anxiety, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BIP), and schizophrenia (SCZ)) and six lipid traits: triglycerides (TG), total cholesterol (TC), high-/low-density lipoprotein cholesterol (HDL/LDL) and apolipoproteins (Apo A-1, Apo B). The inverse-variance weighted (IVW) method served as the primary analytical approach, complemented by MR-Egger regression to evaluate horizontal pleiotropy. RESULTS: Forward MR analysis suggested a significant causal relationship between LDL and MDD (p < 0.001, OR (95%CI) = 0.888 (0.833-0.946)), TG and anxiety (p = 0.016, OR (95%CI) = 1.057(1.010-1.105)). Reverse MR analysis indicated that genetic liability to MDD ( p = 0.017, OR (95%CI) = 1.096(1.016-1.182), and ADHD ( p = 0.009, OR (95%CI) = 1.039( 1.009-1.069)) elevated TG levels, anxiety disorders increased HDL (p = 0.003, OR (95%CI) = 1.288( 1.029-1.520)), LDL (p = 0.001,OR (95%CI) = 1.176(1.066-1.298)), Apo A-1 (p = 0.012,OR(95%CI) = 1.306(1.060-1.609)), and Apo B (p = 0.007,OR(95%CI) = 1.134(1.036-1.241)), whereas SCZ was inversely correlated with lipid profiles. No causal relationships were observed for bipolar disorder. CONCLUSIONS: These findings suggest that genetically predicted TG levels may influence anxiety risk, while genetic predisposition to MDD and ADHD may contribute to dyslipidemia. Our study provides genetic evidence supporting a potential causal interplay between lipid metabolism and mental disorders, highlighting the need for interdisciplinary care and personalized monitoring to address psycho-metabolic comorbidities.
Neural correlates of social cognition in BPD: a review of MRI evidence.
D'Adda F, Scala M, Magro M … +5 more , Mitolo M, Sighinolfi G, Tonon C, Lodi R, Menchetti M
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41460308 · Publisher ↗
BACKGROUND: Borderline Personality Disorder (BPD) is characterized by unstable relationships, affective dysregulation, and impulsivity. A growing body of evidence suggests that deficits in socio-cognitive domains (i.e.,...
BACKGROUND: Borderline Personality Disorder (BPD) is characterized by unstable relationships, affective dysregulation, and impulsivity. A growing body of evidence suggests that deficits in socio-cognitive domains (i.e., mentalization, empathy, and emotion recognition) contribute to the core psychopathology of BPD. However, the neural circuits underlying these deficits remain inconclusive. METHODS: We conducted a review of studies retrieved from PubMed, Scopus, and PsycINFO. We included structural MRI (sMRI) and functional MRI (fMRI) studies that compared individuals with BPD or borderline traits to healthy or clinical control groups. Eligible studies assessed social cognition using task-based paradigms (i.e., emotion recognition, empathy, Theory of Mind) or resting-state protocols focused on connectivity within social brain networks. RESULTS: Twenty-nine studies met the inclusion criteria. Most employed task-based fMRI (k = 24), with fewer using resting-state fMRI (k = 2) or structural MRI (k = 3). Common findings indicate hyperactivation of the amygdala under emotionally salient conditions, altered anterior cingulate cortex (ACC) responses (either hyper- or hypoactivation depending on stimulus valence), and insular hyperresponsivity to social threat contexts. Frontal hypoactivation (i.e., IFG) commonly co-occurred with limbic imbalance. Temporal and temporoparietal areas (STS, TPJ) showed variable patterns, with emotional empathy linked to increased activity and cognitive empathy to reduced activation. CONCLUSIONS: Aberrant activation and connectivity in fronto-limbic and temporoparietal networks contribute to socio-cognitive dysfunction in BPD, underlying emotional dysregulation, impulsivity, interpersonal instability, and self-disturbance. Future standardized paradigms and longitudinal designs should clarify the progression of these neural disruptions and guide targeted psychotherapeutic and neuromodulatory interventions.
Sex-specific association of IDO1 gene with schizophrenia and imbalanced levels of cytokines and neuroactive kynurenine metabolites in relapsed patients.
Ben Afia A, MacDowell KS, Martín-Hernández D … +4 more , Zaafrane F, Gaha L, Leza JC, Bel Hadj Jrad B
Eur Arch Psychiatry Clin Neurosci · 2025 Dec · PMID 41454980 · Publisher ↗
Alterations in tryptophan (Trp) metabolism are of potential significance for the pathophysiology of Schizophrenia (SCZ). However, the genetics of kynurenine pathway (KP) enzymes remains poorly investigated. The aim of th...
Alterations in tryptophan (Trp) metabolism are of potential significance for the pathophysiology of Schizophrenia (SCZ). However, the genetics of kynurenine pathway (KP) enzymes remains poorly investigated. The aim of this study was (i) to examine the rs34820341, rs10109853, rs1480544, and rs2275163 polymorphisms in the IDO1, IDO2, KAT II, and KMO genes, respectively, in a Tunisian population comprising 247 SCZ patients and 265 controls; (ii) to assess the relationship between the IDO1 inducer (IFNγ) and inhibitor (IL-10), together with the neuroactive quinolinic acid (QA) and kynurenic acid (KA), in plasma samples from relapsed patients (n = 23) at admission and after antipsychotic treatment compared with healthy subjects (n = 28); and (iii) to quantify IDO1 and IDO2 mRNA expression in PBMCs from these groups. Our results revealed that the rs34820341 V1 allele and V1/V2–V1/V1 genotypes exhibit a significant risk for male predisposition to SCZ (PA=0.01; PA=0.006, respectively), more specifically to undifferenciated subtype (PA=0.02; PA=0.013, respectively). Diplotypic examination of rs34820341_rs10109853 in IDO1 and IDO2 genes unveils that V2-T combination confers protection from paranoid SCZ (OR = 0.21, PA=0.0024) in males. Relapsed patients, who initially display high levels of pro-inflammatory IFNγ (p = 0.005) and neurotoxic QA (P = 0.007) compared to the control group, maintain increased IFNγ levels (P = 0.004) and show a tendency to QA reduction (P = 0.08) under antipsychotic treatment. Only IDO1 mRNA expression was significantly upregulated in both admitted and discharged SCZ patients (P < 0.0001). Our study supports a role of the IDO1 gene in SCZ susceptibility, but further individual and diplotypic genetic analyses are necessary to further explore IDO1/2 genes.
Association between specific neuroticism symptoms and cardiovascular disease: insights from genetic analysis.
Zhang H, Shu X, Wang Y
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41454979 · Publisher ↗
Although neuroticism has been linked to cardiovascular disease (CVD), the etiological relevance of individual neuroticism symptoms remains poorly understood. In this study, we employed Linkage disequilibrium score regres...
Although neuroticism has been linked to cardiovascular disease (CVD), the etiological relevance of individual neuroticism symptoms remains poorly understood. In this study, we employed Linkage disequilibrium score regression (LDSC) and systematic Mendelian randomization (MR) analyses to examine the potential causal effects of specific neuroticism symptoms on CVD. We obtained summary-level data on 13 specific neuroticism symptoms from the UK Biobank (ranging from 366,726-380,506 participants). Summary statistics for CVD originated from three European-descent GWASs with a total of 799,534 participants. LDSC was performed to investigate the genetic associations between specific neuroticism symptoms and CVD. The inversevariance weighted approach was applied to test the causality for the studied associations, together with extensive validation and sensitivity analyses to verify the main results. LDSC revealed significant genetic correlations between most neuroticism symptoms and CVD ri(r range: 0.0837-0.2041), except for "feeling tense" and "worrying after embarrassment". Furthermore, MR analyses indicated that genetically predicted neuroticism sum-score was causally associated with increased risk of ischemic stroke (IS) (OR = 1.23; 95% CI = 1.05-1.44) and myocardial infarction (MI) (OR = 1.20; 95% CI = 1.02-1.41). Among individual symptoms, irritableness was associated with intracerebral hemorrhage (OR = 4.15; 95% CI = 1.17-14.68), mood swings was associated with IS (OR = 1.30; 95% CI = 1.01-1.68), coronary artery disease (OR = 1.72; 95% CI = 1.35-2.20), and MI (OR = 1.74; 95% CI = 1.29-2.35), and feeling fed up was associated with IS (OR = 1.32; 95% CI = 1.02-1.71). These results remained robust across multiple sensitivity analyses. Overall, our study provided genetic and causal evidence supporting the role of neuroticism sum-score, irritableness, mood swings, and feeling fed up as risk factors for CVD, highlighting potential targets for early intervention and prevention.
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