European Archives Of Psychiatry And Clinical Neuroscience[JOURNAL]
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200 papers
Associations between the novel endothelial activation and stress index and mortality in depressed adults: mediation analysis of systemic inflammation in a large NHANES sample.
Abdu FA, Hu H, Lu P
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42053594 · Publisher ↗
BACKGROUND: Endothelial dysfunction contributes to poor outcomes in depression. However, the prognostic significance of the endothelial activation and stress index (EASIX), a novel marker for endothelial dysfunction, for...
BACKGROUND: Endothelial dysfunction contributes to poor outcomes in depression. However, the prognostic significance of the endothelial activation and stress index (EASIX), a novel marker for endothelial dysfunction, for mortality risk in depression remains unknown. This study aimed to: (1) evaluate the prognostic value of EASIX for mortality risk in US adults with clinically significant depressive symptoms, and (2) explore the potential mediating role of systemic inflammation using multiple hematologic indices. METHODS: We included 1717 adults with clinically significant depressive symptoms (PHQ-9 ≥ 10) from NHANES 2005-2018 after applying predefined exclusion criteria, with mortality follow-up through December 2019. Nonlinear associations were assessed using RCS, and survival differences were evaluated with Kaplan-Meier curves. Cox proportional hazards models estimated hazard ratios (HRs). We additionally performed supplementary weighted analyses. Exploratory mediation analyses examined the neutrophil-to-lymphocyte ratio (NLR), eosinophil-to-lymphocyte ratio (ELR), monocyte-to-lymphocyte ratio (MLR), and the systemic inflammation response index (SIRI). Additionally, we conducted sensitivity analyses excluding early deaths (≤ 2 years) and participants with CKD, abnormal platelet counts, or extreme LDH levels. RESULTS: Over a median follow-up of 83 months (IQR, 46-125 months), 251 all-cause and 56 cardiovascular mortalities occurred. Participants in the highest EASIX quartile showed higher mortality rates. RCS analyses indicated a mostly linear association for all-cause mortality and a nonlinear relationship for cardiovascular mortality. In fully adjusted Cox analyses, participants in the highest EASIX quartile had a 1.82-fold higher risk of all-cause mortality (95% CI: 1.13-2.95). For cardiovascular mortality, the point estimate indicated an increased risk (HR = 1.26); however, it was not statistically significant (95% CI: 0.47-3.41). Sensitivity analyses confirmed robustness, with significant associations persisting after excluding early deaths (HR 2.25, 95% CI 1.34-3.78) and after excluding participants with conditions affecting EASIX components (HR 1.93, 95% CI 1.12-3.34). Exploratory mediation analyses showed that systemic inflammation explained a significant portion of the EASIX-mortality link, with mediated proportions ranging from 7.3% (SIRI) to 29.2% (MLR) for all-cause mortality and from 6.3% (SIRI) to 26.8% (MLR) for cardiovascular mortality. CONCLUSION: Elevated EASIX is strongly associated with increased all-cause mortality in individuals with clinically significant depressive symptoms, with systemic inflammation mediating a substantial portion of this risk.
Disturbances in time perception in patients with obsessive-compulsive disorder.
Mavrogiorgou P, Amanpour H, Jedamzik T … +1 more , Juckel G
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42053593 · Publisher ↗
BACKGROUND: The experience of time and the temporal order of external and internal events is essential for humans. Impairments in the experience of time have long been discussed in relation to main psychiatric disorders,...
BACKGROUND: The experience of time and the temporal order of external and internal events is essential for humans. Impairments in the experience of time have long been discussed in relation to main psychiatric disorders, but rarely in relation to obsessive-compulsive disorder. This pilot study therefore investigated impairments in the experience of time in terms of time perception and time awareness in patients with obsessive-compulsive disorder, as well as possible neurobiological correlates. METHOD: Twenty patients (11 men and 9 women, mean age 43.3, SD = 14.3) with an ICD-10 diagnosis of obsessive-compulsive disorder (F42.X) and 20 healthy subjects matched by age and gender (13 men and 7 women, mean age 40.2, SD = 15.4) were examined using time experience questionnaires, time estimation tasks, and flicker fusion frequency. RESULTS: Significant differences were found in the experience of time between patients with obsessive-compulsive disorder and healthy control subjects. The patient group scored lower on time knowledge, time perception, and time management. It is worth mentioning the positive significant correlation (r = 0.641; p = 0.002) between the severity of compulsive behavior and impaired time management. DISCUSSION: Disturbances in the experience of time appear to play an important role in psychiatric disorders, also in OCD. It is suggested that the process changes in the experience of time should be given greater consideration in current psychopathological findings.
Cannabidiol for the treatment of positive and negative symptoms in schizophrenia spectrum disorders: a systematic review and meta-analysis.
Di Francesco A, Cutrufelli P, Chiarenza C … +10 more , Zambuto L, Concerto C, Mineo L, Petralia A, Catalfo M, Rodolico A, Samara M, Leucht S, Caraci F, Signorelli MS
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42047775 · Publisher ↗
BACKGROUND: Cannabidiol (CBD) has shown therapeutic potential as an antipsychotic in preclinical studies, although the pharmacodynamics profile remains to be fully explained. Current research focuses on CBD as an adjunct...
BACKGROUND: Cannabidiol (CBD) has shown therapeutic potential as an antipsychotic in preclinical studies, although the pharmacodynamics profile remains to be fully explained. Current research focuses on CBD as an adjunctive strategy, a design that allows addressing residual symptoms while avoiding the ethical and clinical risks associated with discontinuing standard antipsychotic medication. This systematic review and meta-analysis evaluated the efficacy of CBD as an adjunctive therapy for positive and negative symptoms in schizophrenia spectrum disorders. METHODS: PubMed and CENTRAL were searched up to May 14, 2025. We included randomized controlled trials (RCTs) comparing CBD augmentation to placebo in adults with these disorders. Primary outcomes were changes on the Positive and Negative Syndrome Scale (PANSS). RESULTS: Five RCTs were included. Meta-analysis showed a statistically significant advantage for CBD over placebo for PANSS total scores (Mean Difference, MD -1.91; 95% Confidence Interval, CI -3.726 to -0.102), positive subscale (MD -1.304; CI -1.917 to -0.692), and general subscale (MD -1.094; CI -1.57 to -0.618). No significant effect was found for the negative subscale. Dropout rates were not significantly different (Odds Ratio, OR 0.93; 95% CI 0.55 to 1.59). Heterogeneity was low across outcomes. CONCLUSION: Our findings demonstrate a statistically significant, albeit small, advantage for adjunctive CBD over placebo for total, positive, and general symptoms in schizophrenia. The lack of effect on negative symptoms suggests a targeted mechanism. Given the consistency across studies, adjunctive CBD is a promising option for specific symptom clusters, but its clinical impact requires confirmation in larger trials.
A unified voice for evidence-based psychiatry: a global response to the WHO guidance on ECT.
Sartorius A, Zilles-Wegner D
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 42047774 · Full text
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From modular connectomics to decision-grade relapse prevention in alcohol dependence: a pragmatic roadmap for validation, utility, and equity.
Vijayasimha M, Srikanth M
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42036484 · Publisher ↗
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Validation of smartphone-based heart rate variability measurement against ECG in patients with depression.
Comfort LD, Müller M, Seifritz E … +1 more , Olbrich S
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42033465 · Publisher ↗
Heart rate variability (HRV) describes time fluctuations between consecutive heart beats, providing insight into the sympathetic and parasympathetic branches of the autonomic nervous system. In depressed patients, HRV ha...
Heart rate variability (HRV) describes time fluctuations between consecutive heart beats, providing insight into the sympathetic and parasympathetic branches of the autonomic nervous system. In depressed patients, HRV has shown reduction due to autonomic dysregulation. Traditionally, its measurement is conducted using electrocardiography (ECG). A novel approach is measurement through a conventional smartphone via photoplethysmography (SPPG), which has not yet been explored in depressed patients. Thus, we developed PULSAR, an SPPG application which measures the user’s pulse wave using the smartphone camera and flash, without the need for external devices, to calculate HRV. To validate PULSAR, simultaneous 5-minute resting-state ECG and SPPG measurements were conducted in 15 healthy individuals and 15 depressed patients. In terms of analytical validation, the SPPG-derived HRV parameters demonstrated high correlations to their ECG- derived counterparts while systematically overestimating most variables. This misestimation is attributed to physiological pulse wave characteristics, motion artifacts and the low sampling rate in SPPG measurements. Regarding clinical validation, HRV parameters in the depressed population were significantly reduced compared to healthy controls in both ECG and SPPG recordings. The frequency-domain parameter LF power, which primarily reflects sympathetic nervous system activity, emerged as the most robust variable for both clinical and analytical validation. Its SPPG-derived value showed a strong correlation with its ECG counterpart (r = 0.84) and a significant reduction in depressed patients (p = 0.021). Future iterations of the PULSAR application should include covariate adjustment, focus on addressing its overestimation of HRV parameters, implementing longitudinal measurements in depressed patients, and potentially incorporating biofeedback techniques to introduce a therapeutic dimension.
Frozen emotions, frozen bodies: a systematic review of limbic system alterations in catatonia.
Marcolini F, Beghelli V, Tartarini D … +5 more , Di Giacomo V, Tempia Valenta S, Mastellari T, De Ronchi D, Atti AR
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42029750 · Publisher ↗
INTRODUCTION: Catatonia is a complex neuropsychiatric syndrome characterized by psychomotor and affective symptoms. While current neurobiological models have focused on cortical and cerebellar dysfunctions, the limbic sy...
INTRODUCTION: Catatonia is a complex neuropsychiatric syndrome characterized by psychomotor and affective symptoms. While current neurobiological models have focused on cortical and cerebellar dysfunctions, the limbic system—crucial for emotional regulation and motivation—remains comparatively underexplored. Emerging evidence suggests that limbic abnormalities may contribute to the pathophysiology of catatonia, offering a more integrated understanding of its clinical manifestations. AIMS: This systematic review aims to synthesize current evidence on neurobiological abnormalities within the limbic system in individuals with catatonia and to identify which structures may be implicated in symptom development. METHODS: Following PRISMA guidelines, systematic searches were conducted across MEDLINE, Web of Science, PsycINFO, and Scopus without date restrictions. Eligible studies included patients with a codified catatonia diagnosis undergoing instrumental or biological investigations involving limbic structures. Data extraction covered study design, diagnostic criteria, limbic regions assessed, and neuroanatomical or functional findings. RESULTS: A total of 1792 studies were identified through database searching, of which 54 full-text articles were assessed; 14 studies met the inclusion criteria and were included. Six additional studies were identified through reference screening, resulting in 20 included articles: 13 observational studies and seven case reports. Most investigations highlighted alterations in the anterior cingulate cortex, including abnormal gyrification, grey matter reduction, and perfusion changes associated with catatonic symptoms. Orbitofrontal cortex abnormalities—though not classically part of the limbic system—were also frequently reported. Evidence regarding other regions was heterogeneous and included volumetric abnormalities of the amygdala and hypothalamus, as well as genetic or acquired factors affecting limbic biochemical regulation. CONCLUSIONS: This systematic review highlights the available neuroanatomical findings in patients with catatonia, supporting the involvement of limbic structures in the development and maintenance of this syndrome. However, variability in catatonia assessment, small sample sizes and study designs limit definitive conclusions. Future studies are needed to better understand the neural underpinnings of catatonia and inform treatment strategies.
Improving functioning in severe mental illness with cognitive remediation: study protocol for a pragmatic randomised multi-centre trial with adjunct sham-controlled tDCS (HEADDSET+).
Buist NC, Poppe A, Ćurčić-Blake B … +2 more , Pijnenborg GHM, van der Meer L
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42029749 · Publisher ↗
Individuals with severe mental illness (SMI) face daily challenges, often due to cognitive impairments. While cognitive remediation (CR) can improve both cognitive and functional outcomes, especially when combined with o...
Individuals with severe mental illness (SMI) face daily challenges, often due to cognitive impairments. While cognitive remediation (CR) can improve both cognitive and functional outcomes, especially when combined with other rehabilitation interventions, its effectiveness in individuals with SMI requiring sheltered housing remains unclear. This trial primarily investigates whether CR improves daily and cognitive functioning compared to a waitlist period. As a second exploratory aim, we will examine whether adding transcranial direct current stimulation (tDCS) enhances the effectiveness of CR in a randomised sham-controlled comparison. Lastly, the trial examines participants’ subjective experiences of the CR intervention. We hypothesise improvements in goal attainment, daily functioning, and cognition. Using a non-concurrent multiple baseline design, 126 participants (aged 18–65) with SMI residing in sheltered housing facilities will receive 16–20 weeks of twice-weekly CR sessions lasting 30–45 min, combined with either active (N = 63) or sham tDCS (N = 63). Functional, cognitive, and clinical assessments will be conducted at baseline, post-waitlist, post-treatment, and 6-month follow-up. Additionally, participants’ meta-cognitive skills and subjective experiences will be evaluated post-treatment. In multilevel mixed models, we will evaluate the effect of CR (combining both CR groups) vs. waitlist, and compare CR + active tDCS vs. CR + sham tDCS to explore potential augmentation effects. If effective, integrating CR, with or without tDCS, into standard care may benefit recovery in individuals with SMI requiring long-term support. ClinicalTrials.gov: NCT06378463, registered on April 17, 2024.
National trends and disparities in Alzheimer disease's mortality (1999-2023) with scenario projections and a data-driven LSTM sensitivity analysis to 2043.
Bdair M, Zahran A, Jallad H … +13 more , Barham I, Qubbaj A, AbuRabi'e M, Jarrar B, Aburajab J, Alsafareeni Z, Mansor A, Ghannam S, Daor A, Daralbarmeel A, Awwad AR, Khader M, Awawdeh A
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42026319 · Publisher ↗
BACKGROUND: Alzheimer’s disease (AD) mortality has increased in the United States, with persistent sociodemographic and geographic disparities. We paired national surveillance with segmented trend modeling and conditiona...
BACKGROUND: Alzheimer’s disease (AD) mortality has increased in the United States, with persistent sociodemographic and geographic disparities. We paired national surveillance with segmented trend modeling and conditional long-horizon projections. METHODS: Using CDC WONDER (NVSS) multiple-cause-of-death data, we analyzed U.S. deaths from 1999 to 2023 with ICD-10 code G30 listed anywhere on the death certificate. The primary outcome was the age-adjusted mortality rate (AAMR) per 100,000 (2000 U.S. standard), stratified by sex, race/ethnicity, state, and place of death. Trend inflection points were identified using joinpoint log-linear regression (WBIC selection), estimating annual percent change (APC). Projections for 2024–2043 were presented primarily as scenario-based trajectories anchored to 2023 (flat, continuation of pre-2020 growth, continuation of post-2020 decline). A univariate LSTM forecast with Monte Carlo dropout intervals was reported as a sensitivity analysis and benchmarked via back-testing (train 1999–2010; test 2011–2023) against classical models. RESULTS: From 1999 to 2023, 2,970,206 AD-associated deaths were recorded; AAMR increased from 45.01 to 52.72 per 100,000. Joinpoint analysis identified inflections in 2005, 2012, and 2020, with APCs of + 3.50%/year (1999–2005), − 2.46%/year (2005–2012), + 3.61%/year (2012–2020), and − 5.62%/year (2020–2023). Women had higher rates than men, and White individuals had the highest race-specific AAMR. Most deaths occurred in nursing homes/long-term care (55.68%). State crude rates ranged 22.70–103.39 per 100,000. Scenario projections for 2043 ranged from 12.51 (continued post-2020 decline) to 132.64 (continued pre-2020 growth), while the LSTM projected modest fluctuations in the low-to-mid 50s (e.g., 2043: 53.14; 95% PI 43.91–62.54). CONCLUSION: U.S. Alzheimer’s mortality shows a multi-phase trend with persistent sex, racial/ethnic, and geographic disparities and most deaths occurring in long-term care. The post-2020 decline should be interpreted cautiously due to competing mortality and certification/coding changes during COVID-19. Long-horizon projections are best viewed as conditional scenarios shaped by aging, diagnosis, and future treatments, supporting equity-focused prevention and strengthened long-term care and home support.
Sustained benefits of closed-loop transcranial alternating current stimulation (CL-tACS) on depression: a 12-week open-label clinical trial.
Schwippel T, Pupillo F, Feldman ZW … +4 more , Walker C, Townsend L, Rubinow D, Frohlich F
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42026318 · Publisher ↗
BACKGROUND: Major depressive disorder (MDD) is associated with disruptions in alpha oscillations in the prefrontal cortex. Closed-loop transcranial alternating current stimulation (CL-tACS) is a novel intervention design...
BACKGROUND: Major depressive disorder (MDD) is associated with disruptions in alpha oscillations in the prefrontal cortex. Closed-loop transcranial alternating current stimulation (CL-tACS) is a novel intervention designed to modulate these oscillations in real-time and alleviate depressive symptoms. However, its long-term efficacy remains unclear. METHODS: In this open-label clinical trial, 15 individuals with MDD received bifrontal CL-tACS (2 mA, individual alpha frequency) over five sessions. Stimulation was triggered by real-time EEG alpha power. Clinical assessments were performed on Day 1, Day 5, at 1 week, and every 2 weeks thereafter through 12 weeks. The primary outcome was change in depressive symptoms on the QIDS. Secondary longitudinal outcomes included quality of life (Q-LES-Q-SF), anhedonia (SHAPS), state anxiety (STAI), and depression, anxiety, and stress symptoms (DASS-42). Planned Day 1-to-12-week contrasts were used to assess durability. Short-term clinician-rated outcomes at 2 weeks included clinician-rated HDRS-17 and CGI-S. RESULTS: At 12 weeks, depressive symptoms decreased significantly (QIDS: − 7.3 points, p < .001, d = 1.75). Quality of life improved (+ 16.9%, pbonf = .008, d = 1.02), anhedonia decreased (− 4.5 points, pbonf < .001, d = 1.43), and depression, anxiety, and stress symptoms on the DASS-42 were reduced (all pbonf ≤ .016), whereas state anxiety (STAI) remained unchanged. At 2 weeks, clinician-rated depression and global illness severity were significantly reduced (HDRS-17: − 12.3 points; CGI-S: − 2.3 points; both pbonf < .001). Adverse events were mild and stimulation-related sensations were minimal. CONCLUSIONS: CL-tACS was associated with rapid and sustained improvement in depressive symptoms over 12 weeks, along with improvements in quality of life and anhedonia. These findings support further evaluation of CL-tACS in larger placebo-controlled trials.
Retrospective childhood attention-deficit/hyperactivity disorder traits and their differential associations with mood disorder presentations in adulthood.
Jwa Y, Lee J, Yu H … +11 more , Lee CW, Hur HJ, Do HS, Lim J, Lim SW, Kim JH, Hwang IA, Kang HS, Ha TH, Park J, Myung W
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42026317 · Publisher ↗
BACKGROUND: Childhood symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) often persist in adulthood and overlap considerably with mood disorder presentations. This study examines how specific childhood ADHD trai...
BACKGROUND: Childhood symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) often persist in adulthood and overlap considerably with mood disorder presentations. This study examines how specific childhood ADHD traits relate to distinct clinical characteristics in adults with mood disorders. METHODS: We analyzed data from 755 adults diagnosed with major depressive disorder (n = 287) or bipolar disorder (n = 468). Participants retrospectively reported childhood ADHD traits using the 25-item Wender Utah Rating Scale. We mapped associations between childhood ADHD total score and three childhood ADHD traits (Impulsivity/Behavioral Problems, Inattentiveness/School Problems, Self-esteem/Negative Mood) and a comprehensive set of clinical variables, including depression, anxiety, affective temperament, emotional instability, adult ADHD symptoms, emotion regulation skills, childhood trauma, interpersonal sensitivity, resilience, problematic alcohol use. Partial correlations were used to identify initial links, followed by the path analysis to further explore these associations. RESULTS: Childhood ADHD traits showed its strongest associations with trait-based mood instability, childhood trauma exposure, adult ADHD symptoms, and interpersonal sensitivity. Among mood temperaments, depressive temperament showed the strongest association, while hyperthymic the weakest. Emotion regulation skills showed minimal association. No significant subgroup differences were found among diagnostic groups or sexes according to multigroup SEM. Dimensionally, Self-esteem/Negative Mood uniquely predicted greater depressive and anxiety symptoms, behavioral inhibition, higher interpersonal sensitivity, lower resilience, and problematic alcohol use. Inattentiveness/School Problems was the strongest and most consistent predictor of adult ADHD symptoms. Impulsivity/Behavioral Problems selectively related to irritable temperament, behavioral activation, and lower interpersonal sensitivity. CONCLUSIONS: Childhood ADHD traits show distinct, dimension-specific associations with adult mood disorder phenotypes. Viewing ADHD as distinct traits may guide more personalized treatment strategies.
Physical exercise as a non-pharmacological strategy for ADHD considering neurobiological mechanisms, cognitive benefits, and practical recommendations: a narrative review.
Vergara Nieto ÁA, Diaz AH, Millán MH … +2 more , Oyarzo DS, Gacitúa JA
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42026316 · Publisher ↗
Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity, frequently associated with catecholaminergic dysregulation, neuroi...
Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity, frequently associated with catecholaminergic dysregulation, neuroimmune imbalance, and alterations in frontostriatal and prefrontal networks. Although pharmacological and behavioral treatments remain first-line, up to one-third of patients exhibit limited response or adverse effects, underscoring the need for complementary strategies. Physical exercise has emerged as a promising non-pharmacological intervention with acute and chronic benefits on core symptoms and functional outcomes. This narrative review critically synthesizes evidence from 2010 to 2025, integrating clinical, mechanistic, and prescription-focused findings. Acute exercise reliably enhances sustained attention and inhibitory control, while long-term aerobic, resistance, combined, and mind–body programs improve executive functions, sleep, mood regulation, and classroom behavior. These outcomes are supported by well-described neurobiological mechanisms, including modulation of dopamine and norepinephrine transmission, upregulation of neurotrophins such as BDNF and VEGF, regulation of the HPA axis, attenuation of pro-inflammatory signaling, enhancement of cortical perfusion, and positive shifts in gut microbiota. Martial arts and mind–body modalities further highlight the potential of structured, discipline-based exercise programs, though safety protocols are required for contact practices. Despite encouraging findings, heterogeneity in study design, exercise prescription, and population characteristics limits cross-study comparability, and optimal “doses” for specific subgroups remain undefined. Future trials should adopt harmonized protocols, embed mechanistic endpoints, and clarify responder profiles to enable exercise prescriptions tailored to age, sex, comorbidities, and pharmacological status. Collectively, the evidence positions physical exercise as a generally safe, biologically plausible intervention showing promise as an adjunct in ADHD management, with potential for integration into multimodal care models.
Comparison of TDP-43, NfL, and GFAP in cerebrospinal fluid and serum in Alzheimer's disease.
Manco C, Righi D, Sangiorgio AR … +3 more , Pucci B, De Stefano N, Plantone D
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42026315 · Publisher ↗
The diagnosis of Alzheimer’s disease (AD) has transitioned from a clinical to a clinical-biological framework, with biomarkers playing a crucial role in diagnosis and patient stratification. This retrospective study aime...
The diagnosis of Alzheimer’s disease (AD) has transitioned from a clinical to a clinical-biological framework, with biomarkers playing a crucial role in diagnosis and patient stratification. This retrospective study aimed to: evaluate correlations between neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and transactive response DNA-binding protein 43 kDa (TDP-43) levels in CSF and serum (measured via SIMOA) in AD patients; compare serum levels with healthy controls (HCs); analyze relationships with core AD biomarkers; and explore associations with cognitive impairment. Serum NfL and GFAP levels were significantly elevated in AD patients compared to HCs (p < 0.001). Strong positive correlations were observed between CSF and serum levels for both NfL (p < 0.001) and GFAP (p < 0.001). CSF NfL correlated with CSF GFAP (p < 0.001), while serum NfL correlated with serum GFAP (p < 0.001) and CSF GFAP (p = 0.006). Both CSF NfL (r = 0.3, p = 0.02) and serum NfL (r = 0.3, p = 0.008) positively correlated with age (p = 0.01). Passing–Bablok regression revealed slopes of 0.01 for NfL and 0.02 for GFAP. Regression models demonstrated high diagnostic accuracy for NfL (specificity/sensitivity: 81%/82%) and GFAP (90%/92%). No significant differences were found in serum TDP-43 levels between AD patients and HCs, nor were correlations observed with other biomarkers and age. A negative correlation was detected between pTau/Aβ 1–42 ratio and MMSE scores (p < 0.02). In conclusion, serum NfL and GFAP exhibit moderate correlations with their CSF counterparts in AD, supporting their potential as less invasive surrogate biomarkers. While serum NfL and GFAP effectively discriminate AD from HCs, serum TDP-43 lacks comparable diagnostic utility.
Interrelationships of childhood trauma, psychiatric symptoms, neurocognition, and insomnia in chronic schizophrenia: a network perspective.
Chen S, Zheng X, Deng J … +2 more , Li Z, Zhang X
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42002609 · Publisher ↗
BACKGROUND: Childhood trauma has a profound influence on the clinical manifestations of schizophrenia. This study aimed to explore the interrelationships among childhood trauma, psychiatric symptoms, neurocognition, and...
BACKGROUND: Childhood trauma has a profound influence on the clinical manifestations of schizophrenia. This study aimed to explore the interrelationships among childhood trauma, psychiatric symptoms, neurocognition, and insomnia in Chinese patients with chronic schizophrenia using a network analysis approach. METHODS: A total of 649 patients with chronic schizophrenia were assessed using the Childhood Trauma Questionnaire–Short Form (CTQ-SF), Positive and Negative Syndrome Scale (PANSS), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and Insomnia Severity Index (ISI). Three networks were constructed and visualized. The expected influence (EI) and bridge expected influence (BEI) indices were calculated to identify central and bridge nodes. RESULTS: The prevalence of insomnia and childhood trauma was 18.3% (n = 119) and 49.5% (n = 321), respectively. Daytime dysfunction and distress caused by sleep problems showed the highest EI values and emerged as central nodes. The PANSS mood factor and difficulty falling asleep showed the highest BEI, indicating prominent cross-domain connectivity. Insomnia symptoms were strongly associated with the PANSS mood factor, particularly difficulty falling asleep. Neurocognitive performance, especially language ability, was primarily related to negative symptoms. Childhood trauma (CTQ-SF total score) was strongly associated with impaired quality of life and positive symptoms, with physical abuse showing the strongest correlation with the latter. CONCLUSION: These findings underscore the clinical relevance of insomnia, affective symptoms, and childhood trauma—particularly physical abuse—in chronic schizophrenia and may help inform assessment priorities in future longitudinal and interventional studies.
The neutrophil-to-lymphocyte ratio: a psychoneuroimmunological nexus linking depression and cardiovascular comorbidity.
Du C, Zhao H, Han Y … +2 more , Yu Y, Yu R
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 42002608 · Publisher ↗
BACKGROUND: A significant worldwide health concern linked to ongoing low-grade inflammatory processes is depression concomitant with cardiovascular disease (CVD). There aren't many pertinent clinical biomarkers, though....
BACKGROUND: A significant worldwide health concern linked to ongoing low-grade inflammatory processes is depression concomitant with cardiovascular disease (CVD). There aren't many pertinent clinical biomarkers, though. This study aims to clarify the underlying mechanisms of the neutrophil-to-lymphocyte ratio (NLR) and ascertain if it is associated with depression-CVD comorbidity. METHODS: Multivariable logistic regression and restricted cubic spline (RCS) analysis were used to examine the nonlinear connection between NLR and depression-cardiovascular comorbidity based on data from the National Health and Nutrition Examination Survey (NHANES). Predictive models were built using seven machine learning techniques, and the outcomes were interpreted using SHapley Additive exPlanations (SHAP). Gene function and pathway enrichment analyses were carried out following network pharmacology screening for core targets. RESULTS: NLR and depression-CVD comorbidity were shown to be significantly correlated (highest quartile odds ratio = 1.44). In terms of prediction, the logistic regression model performed better (AUC = 0.88). Ten important targets, including TNF and IL-6, were found via network pharmacological analysis. These targets were found to be strongly linked to the AGE-RAGE signalling cascade, lipid metabolism, inflammatory reactions, and atherosclerosis, according to enrichment analysis. CONCLUSION: NLR may be a biomarker for the co-occurrence of depression and CVD. Its activities are part of an immunological, metabolic, and inflammatory network that is controlled by important targets like TNF and IL-6. The study offers a fresh viewpoint on the pathophysiology, early identification, and focused management of this comorbidity.
Baseline characteristics of a diagnostically defined early psychosis cohort entering supported employment and education: findings from the SEEearly trial.
Willert A, Mönch M, Jäckel D … +17 more , Leopold K, Grittner U, Nischk D, Senner S, Falkai P, Pogarell O, Sachenbacher S, Gallinat J, Lambert M, Zimmermann A, Bermpohl F, Daniels MA, Heinz A, Schouler-Ocak M, Correll CU, Uhlhaas PJ, Bechdolf A
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41968170 · Publisher ↗
SEEearly is a multi-site randomized controlled trial (RCT) investigating the efficacy of supported employment and education (SEE) in adolescents and young adults aged 16 to 35 with early psychosis. In this publication we...
SEEearly is a multi-site randomized controlled trial (RCT) investigating the efficacy of supported employment and education (SEE) in adolescents and young adults aged 16 to 35 with early psychosis. In this publication we report baseline characteristics of the cohort with an emphasis on educational and vocational status at study entry. Between October 2022 and December 2024, a total of 184 participants with a diagnosis of schizophrenia spectrum disorder were recruited across six sites in Germany. At baseline, 53.3% were not engaged in employment, education, or training (NEET); only 20.1% were competitively employed and 26.6% were enrolled in education or training. A majority of the participants (97.8%) had a second or third level school-leaving qualification, yet only 39.1% of participants had completed post-secondary qualification indicating delayed or interrupted vocational trajectories. The sample is predominantly male (69.6%) and single (87.0%). Nearly 45% of participants had comorbid substance misuse. Functional assessments revealed marked psychosocial impairments, while ratings on symptom severity indicated moderate psychopathology. Compared to previous RCTs on SEE, the SEEearly sample is larger and more diagnostically homogenous. Baseline data show considerable disruptions in vocational trajectories at study entry. The findings highlight early and substantial deviations in vocational trajectories in young adults with early psychosis and underscore the need for interventions that target both educational and vocational attainment.
Early-life tobacco exposure elevating childhood attention-deficit hyperactivity disorder risk: a two-sample Mendelian randomisation analysis.
Shang K, Luo C, Tan X … +4 more , Xu M, Li B, Wang H, Cheng F
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41945141 · Publisher ↗
Evidence linking secondhand tobacco exposures to childhood attention-deficit hyperactivity disorder (ADHD) risk has been reported, however, the causality of the relationship and potential biological pathways is unknown....
Evidence linking secondhand tobacco exposures to childhood attention-deficit hyperactivity disorder (ADHD) risk has been reported, however, the causality of the relationship and potential biological pathways is unknown. We applied a two-step Mendelian randomisation (MR) analysis and Bayesian colocalization analysis to examine the causal relationship between smoking behaviours, secondhand tobacco-induced DNA methylation and childhood ADHD risk. The findings revealed causal positive connections between smoking behaviours of daily cigarette consumption (Odds ratio [OR]Inverse variance weighted (IVW), 1.56 for per 1–SD increase; 95% CI: 1.17–2.09; P = 0.003), smoking cessation (ORIVW, 2.92 for per 1–SD increase; 95% CI: 1.65–5.17; P = 2.23 × 10− 4), smoking initiation (ORIVW, 3.01 for per 1–SD increase; 95% CI: 2.60–3.48; P = 6.41 × 10− 50) and the risk of childhood ADHD. On the contrary, age of initiation of regular smoking suggested a decreased risk with ADHD risk (ORIVW, 0.17 for per 1–SD increase; 95% CI: 0.06–0.47; P = 7.42 × 10− 4). Genetically predicted DNA methylation alterations related to secondhand tobacco exposure at cg23211703 [PTPRF], cg02772619, cg19716073 [CACNG1], and cg22500280 [MAD1L1] were associated with increased ADHD risk, whereas DNA methylation changes at cg03504834 [FOXP2], cg23666170 [PLK1S1], cg24476096 [C1orf84/MED8], cg12142869 [OR10AD1] and cg16572910 were related to decreased ADHD risk. Five CpG sites (cg23211703, cg03504834, cg02772619, cg12142869, and cg19716073) exhibited convincing colocalization evidence. This study provides evidence supporting a causal link between tobacco smoking, DNA methylation and childhood ADHD risk.
Global trends in rehabilitation needs for mental disorders in 204 countries and territories, 1990-2021: a cross-sectional analysis of the global burden of disease study 2021.
Zhao Z, Xu H, Shi J … +6 more , Zhang J, Wu J, Ni J, Zheng J, Wang C, Shan C
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41936689 · Publisher ↗
BACKGROUND: The prevalence of mental disorders has been steadily rising due to aging populations, rapid urbanization, and social structural changes, posing significant public health challenges globally. Despite advances...
BACKGROUND: The prevalence of mental disorders has been steadily rising due to aging populations, rapid urbanization, and social structural changes, posing significant public health challenges globally. Despite advances in pharmacological treatments, limited social functionality, high relapse risk, and adaptation difficulties persist in patients with mental disorders, emphasizing the critical need for rehabilitation services. METHODS: This study utilizes data from the Global Burden of Disease Study 2021 to analyze the burden of mental disorders and rehabilitation needs across 204 countries and territories. Age-standardized rates (ASR) and Years Lived with Disability (YLDs) were calculated, along with the Estimated Annual Percentage Change (EAPC). Patterns were examined for major mental disorders including developmental intellectual disability, schizophrenia, and autism spectrum disorders. Correlations with the Socio-Demographic Index (SDI) were assessed using Spearman analysis. FINDINGS: Between 1990 and 2021, the global prevalence of mental disorders decreased slightly in ASR (-0.19% EAPC), while the absolute number of cases increased by 34.8%. Rehabilitation needs for elderly women and young men surged significantly, particularly in low- and middle-income countries. SDI exhibited distinct associations with rehabilitation burdens, reflecting disparities in resource availability and regional improvements. Developmental intellectual disability displayed strong negative correlations with SDI, while schizophrenia and autism spectrum disorders showed positive correlations. INTERPRETATION: Findings highlight the urgency of prioritizing mental health resource allocation in vulnerable populations and high-burden regions. Integrated approaches incorporating Universal Health Coverage (UHC), SDI-based strategies, and international collaborations are essential to advancing equity in mental health rehabilitation globally.
Nonlinear associations of plasma IL-9 with depression and anxiety symptoms in first-episode, drug-naïve major depressive disorder.
Zhou Y, Han Z, Yang N … +6 more , Li M, Xie M, Zhang C, Wang S, Gao Y, Li J
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41933226 · Publisher ↗
OBJECTIVE: While inflammation is implicated in pathophysiology of major depressive disorder (MDD), the effect of interleukin (IL) profile in first-episode, drug-naïve MDD (FEDN-MDD) patients remains unclear. This study a...
OBJECTIVE: While inflammation is implicated in pathophysiology of major depressive disorder (MDD), the effect of interleukin (IL) profile in first-episode, drug-naïve MDD (FEDN-MDD) patients remains unclear. This study aimed to delineate the plasma IL signature, establish a diagnostic biomarker panel, and characterize cytokine-symptom relationships in FEDN-MDD. METHODS: This cross-sectional study included 170 participants, comprising 101 FEDN-MDD patients and 69 healthy controls (HCs). Depression and anxiety severity were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA-14), respectively. Fasting plasma samples were collected, and concentrations of 13 types of interleukins (IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17) were measured using Luminex xMAP technology. LASSO regression with 10-fold cross-validation was employed for biomarker selection, and polynomial regression was used to model nonlinear associations. RESULTS: After demographic adjustment, 12 of 13 ILs were significantly elevated in MDD versus HCs (all p < 0.001), with IL-9 showing the largest effect size (partial η²=0.544). LASSO regression identified a 3-cytokine panel (IL-7, IL-9, IL-17) with outstanding diagnostic accuracy (AUC = 0.958, sensitivity = 88.1%, specificity = 89.9%). Crucially, IL-9 exhibited an inverted U-shaped relationship with symptom severity (all quadratic p < 0.05), where both depression (HAMD-17) and anxiety (HAMA-14) severity peaked at IL-9 concentrations near 1000 pg/mL (95% Bootstrap CIs: ~800–1070 pg/mL). CONCLUSION: Plasma IL-9 is a pivotal mediator in FEDN-MDD, exhibiting a unique concentration-symptom dynamic and driving a high-accuracy diagnostic triad. This highlights its promise as a candidate target for mechanistic investigation and a potential tool for precision psychiatry.
From controversy to clinical evidence: the evolving role of cannabis in pain therapy.
Demann R, Bonnet U, Juckel G … +1 more , Kuhn J
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41925858 · Publisher ↗
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