European Archives of Psychiatry and Clinical Neuroscience最新文献

Disorganization is a nuclear dimension of psychosis, especially in schizophrenia. Despite its relevant association with poor prognosis and negative outcomes, it is still under-investigated compared to positive and negative symptoms, in particular at the onset of illness. This study explored disorganization in youth at Clinical High Risk for Psychosis (CHR-P) over a 2-year period. A sample of 180 CHR-P participants (50% males; 51.1% with baseline second-generation antipsychotic medication) recruited within a specialized CHR-P service completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Across the follow-up, we examined key associations of disorganization with other domains of psychopathology, functioning, and treatment response using Spearman's rank correlation coefficients and linear regression analyses. Our results showed a significant longitudinal reduction in disorganization severity levels across the follow-up. This decrease was significantly associated with improvements in negative symptoms and daily functioning, with a shorter duration of untreated psychiatric symptoms, and with baseline equivalent dose of antipsychotic medication. No significant longitudinal associations with other treatment component of the PARMS program were found. Our findings suggest a longitudinal improvement in disorganization dimension in CHR-P individuals, especially in the context of early interventions targeting reduction in the duration of untreated psychiatric symptoms and favoring a prompt antipsychotic therapy.

Background: Attention-deficit hyperactivity disorder (ADHD) has a high prevalence of co-occurring impaired self-regulation (dysregulation), exacerbating adverse outcomes. Neural correlates underlying impaired self-regulation in ADHD remain inconclusive. We aimed to investigate the impact of dysregulation on intrinsic functional connectivity (iFC) in children with ADHD and the correlation of iFC with dysregulation among children with ADHD relative to typically developing controls (TDC).

Methods: Resting-state functional MRI data of 71 children with ADHD (11.38 ± 2.44 years) and 117 age-matched TDC were used in the final analysis. We restricted our analyses to resting-state networks (RSNs) of interest derived from independent component analysis. Impaired self-regulation was estimated based on the Child Behavioral Checklist-Dysregulation Profile.

Results: Children with ADHD showed stronger iFC than TDC in the left frontoparietal network, somatomotor network (SMN), visual network (VIS), default-mode network (DMN), and dorsal attention network (DAN) (FWE-corrected alpha < 0.05). After adding dysregulation levels as an extra regressor, the ADHD group only showed stronger iFC in the VIS and SMN. ADHD children with high dysregulation had higher precuneus iFC within DMN than ADHD children with low dysregulation. Angular gyrus iFC within DMN was positively correlated with dysregulation in the ADHD group but negatively correlated with dysregulation in the TDC group. Functional network connectivity showed ADHD had a greater DMN-DAN connection than TDC, regardless of the dysregulation level.

Conclusions: Our findings suggest that DMN connectivity may contribute to impaired self-regulation in ADHD. Impaired self-regulation should be considered categorical and dimensional moderators for the neural correlates of altered iFC in ADHD.

Suicide is a leading cause of death worldwide. Suicide ideation (SI) is a known risk factor for suicide behaviour (SB). The current psychobiology and genetic predisposition to SI and SB are poorly defined. Despite convincing relevance of a genetic background for SI, there is no current implementable knowledge about the genetic makeup that identifies subjects at risk for it. One of the possible reasons for the absence of a clear-cut evidence is the polygenetic nature of SI along with the very large sample sizes that are needed to observe significant genetic association result. The CATIE sample was instrumental to the analysis. SI was retrieved as measured by the Calgary test. Clinical possible covariates were identified by a nested regression model. A principal component analysis helped in defining the possible genetic stratification factors. A GWAS analysis, polygenic risk score associated with a random forest analysis and a molecular pathway analysis were undertaken to identify the genetic contribution to SI. As a result, 741 Schizophrenic individuals from the CATIE were available for the genetic analysis, including 166,325 SNPs after quality control and pruning. No GWAS significant result was found. The random forest analysis conducted by combining the polygenic risk score and several clinical variables resulted in a possibly overfitting model (OOB error rate < 1%). The molecular pathway analysis revealed several molecular pathways possibly involved in SI, of which those involved in microglia functioning were of particular interest. A medium-small sample of SKZ individuals was analyzed to shed a light on the genetic of SI. As an expected result from the underpowered sample, no GWAS positive result was retrieved, but the molecular pathway analysis indicated a possible role of microglia and neurodevelopment in SI.

Cannabis use and treatment demand has risen in the past decade. Previous analyses of treatment demand are limited by methodological constraints or are outdated. Cross-country differences and trends in cannabis treatment demand are described using data from the European Monitoring Centre for Drugs and Drug Addiction. Two novel indicators are employed: firstly, the cannabis-attributable treatment fraction (CATF) is obtained by dividing the number of treatment entrants for cannabis use problems by the number of treatment entrants for any substance use problem, accounting for possible changes in the reporting system. Secondly, comparing the number of treatment entrants for cannabis use problems to the number of people who use cannabis (near) daily yields the treated-user-ratio (TUR), which considers a proxy for treatment need (frequent use). Across 30 countries with available data, the importance of cannabis in European treatment facilities varies greatly (CATF: min = 3%; max = 65%), with lower estimates in Eastern European countries. Across 20 countries with complete data, the CATF has risen from 29.4% in 2013 to 37.1% in 2020. The TUR calculated on 26 countries suggests that about 3 in 100 frequent users have sought treatment for their cannabis use problems. Over time, treatment demand has increased at a slower pace than treatment need in most countries. One in three treatment entrants for substance use problems in Europe are due to cannabis, with large variations between countries. There are indications for a widening treatment gap for cannabis use problems. In countries liberalising cannabis laws, monitoring changes in treatment access and demand is warranted.

There is a potential link between cannabis and mental disorders. Cannabis exposure involves in many cases negative mental emotions, which are unpleasant sensations or thoughts. Whereas mild cases of negative mental emotions inflict patient's quality of life, more severe cases lead to therapy discontinuations, or even hospitalizations and death. This study characterizes cannabis users who experienced negative mental emotions after cannabis exposure. The Releaf App database was utilized to evaluate the association between personal and cannabis use characteristics on reporting a negative mental emotion during cannabis exposure. This global mobile lets individuals track real-time cannabis experience use with cannabinoid-based products, containing data points such as gender, age, reasons for use, product type, cannabis composition, and feelings and emotions experienced after cannabis use. Multivariable logistic regression models were constructed, adjusting for potential confounders such as gender and previous experience with cannabis use. The study population comprised 4,435 users, and 34,279 sessions were collected from various countries, mainly from North America, and included in the primary analysis. Reporting on negative mental emotions was associated with users in the age group of 18-30 years. Using cannabis for a mental purpose was associated with a small increase in reporting on negative mental emotions (OR = 1.10, 95%CI [1.03-1.19]). Oral products were associated with reporting on negative mental emotions. THC-dominant products were associated with reporting negative mental emotions compared to balanced products (OR = 1.21, 95%CI [1.06-1.38]). This study suggests that some characteristics of cannabis use, such as young age and oral consumption are associated with negative mental emotions. Further studies should examine the interface between cannabis consumption, characteristics of consumers, and negative emotional experience or even long-term mental disorders.

Both the BDNF gene rs6265 and the FKBP5 gene rs1360780 polymorphisms are independently associated with adult psychotic-like experiences, when exposed to high childhood abuse; however, it remains unclear whether the relationship between childhood abuse and burnout is moderated by these two single nucleotide polymorphisms (SNPs). Furthermore, there is an interaction between glucocorticoid receptor transcriptional activity and BDNF signaling. Therefore, we investigated the interaction of these two SNPs with childhood trauma in predicting burnout. We recruited 990 participants (mean age 33.06 years, S.D. = 6.31) from general occupational groups and genotyped them for rs6265 and rs1360780. Burnout, childhood trauma, resilience, and job stress were measured through a series of rating scales. Gene-by-environment and gene-by-gene-by-environment interactions were examined using linear hierarchical regression and PROCESS macro in SPSS. Covariates included demographics and resilience. We found that rs6265 moderated the association between job stress and emotional exhaustion. Both rs6265 and rs1360780 moderated the association between childhood abuse and cynicism. There was significant interaction of childhood abuse × rs6265 × rs1360780 on emotional exhaustion and reduced personal accomplishment, so that rs6265 CC genotype and rs1360780 TT genotype together predicted higher levels of emotional exhaustion under high childhood abuse, while rs6265 TT genotype and rs1360780 CC genotype together exerted a resilient effect on reduced personal accomplishment in the face of childhood abuse. Our findings suggest that the rs6265 CC genotype and rs1360780 TT genotype may jointly contribute to increased risk of burnout under childhood trauma.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.

This study aimed to investigate the cross-sectional associations between regional Alzheimer's disease (AD) biomarkers, including tau, β-amyloid (Aβ), and brain volume, within the Papez circuit, and neuropsychological functioning across the preclinical and clinical spectrum of AD. We utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 251 Aβ-positive participants. Participants were categorized into three groups based on the Clinical Dementia Rating (CDR): 73 individuals with preclinical AD (CDR = 0), 114 with prodromal AD (CDR = 0.5), and 64 with clinical AD dementia (CDR ≥ 1). Linear regression analyses, adjusted for age, gender, and education years, were employed to evaluate the associations between five regions of interest (the hippocampus, para-hippocampus, entorhinal cortex, posterior cingulate cortex, and thalamus) and five neuropsychological tests across the three imaging modalities. In the preclinical stage of AD, flortaucipir PET was associated with impaired global cognition and episodic memory (range standardized β = 0.255-0.498, p < 0.05 corrected for multiple comparisons), while florbetapir PET and brain volume were marginally related to global cognition (range standardized β = 0.221-0.231, p < 0.05). In the clinical stages of AD (prodromal and dementia), both increased flortaucipir uptake and decreased brain volume were significantly associated with poorer global neuropsychological and episodic memory performance (range standardized β = 0.222-0.621, p < 0.05, most regions of interest survived correction for multiple comparisions). However, a slight relationship was observed between florbetapir uptake and poorer global cognitive function. The regions most affected by flortaucipir PET were the hippocampus, para-hippocampus, and posterior cingulate cortex. During the clinical stages, the hippocampus and entorhinal cortex exhibited the most significant volumetric changes. Tau PET and brain volume measurements within the Papez circuit are more sensitive indicators of early cognitive deficits in AD than Aβ PET. Furthermore, during the clinical stages of AD, both flortaucipir PET and brain volume of the Papez circuit are closely correlated with cognitive decline. These findings underscore the importance of integrating multiple biomarkers for the comprehensive evaluation of AD pathology and its impact on cognition.