European Archives of Psychiatry and Clinical Neuroscience最新文献

The β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) gene polymorphism (rs638405) has been widely reported to be associated with Alzheimer's disease (AD) risk. However, studies on the relationship between BACE1 gene polymorphism (rs638405), brain volume, and cognition in AD patients remain scarce. To investigate the effect of genetic polymorphism in BACE1 on gray matter volume (GMV) and cognition in AD, this study recruited 111 cognitively unimpaired (CU) controls and 144 AD patients. The effect of BACE1 rs638405 polymorphism on cognition was explored in CU and AD groups. Then the interaction effect of the diagnosis and BACE1 rs638405 polymorphism on GMV was performed, following the post-hoc analysis of regions of interest (ROIs) in interaction analysis. Mediation analysis was used to elucidate the relationship among genotypes, ROIs and cognition. BACE1 rs638405 G carriers (BACE1 G+) showed significantly lower scores in global cognition and memory function than noncarriers (BACE1 G-) in AD group. Genotypes (G+/G-) and diagnosis (CU/AD) have interaction on GMV of medial temporal lobe (MTL) including the left parahippocampus and right hippocampus. Post-hoc analysis revealed that BACE1 G+ exhibited significantly lower GMV in ROIs compared to BACE1 G- in AD. Finally, mediation analysis further demonstrated that the GMV of ROIs mediated the effect of BACE1 rs638405 polymorphism on cognition in AD. Our results emphasize the BACE1 rs638405 gene polymorphisms may affect the GMV of MTL and cognition in AD, deepening the understanding of AD pathogenesis.

Previously we found altered microglia-neuron interactions in the prefrontal cortex in schizophrenia. We hypothesized that microglia-neuron interactions may be dysregulated in the caudate nucleus in schizophrenia. A postmortem ultrastructural morphometric study was performed to investigate satellite microglia (SatMg) and adjacent neurons in the head of the caudate nucleus in 21 cases of schizophrenia and 20 healthy controls. We found increased microglial density in young schizophrenia patients compared to elderly controls. Volume density (Vv) and the number (N) of mitochondria were lower and total area of vacuoles of endoplasmic reticulum was higher in SatMg in the schizophrenia group compared to controls. The mitochondrial decline has progressed with age and illness duration. Areas of neuronal somata, nucleus, mitochondria and vacuoles of endoplasmic reticulum were significantly higher in schizophrenia compared to controls. These neuronal parameters were positively correlated with area and Vv of vacuoles of endoplasmic reticulum in SatMg in the schizophrenia group but not in the control group. Besides, area of mitochondria in neurons was negatively correlated with N of mitochondria in SatMg. Vv of lipofuscin granules in neurons was higher in elderly patients compared to young patients and was positively correlated with age, illness duration and Vv of lipofuscin granules in SatMg in the schizophrenia group. The disturbances of SatMg-neuronal interactions may be related to the endoplasmic reticulum stress, alterations and deficit of mitochondria in SatMg due to chronic stress, activation and priming of SatMg followed by neurotoxicity. SatMg may participate in neuronal aging in schizophrenia.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal. The Psych-STRATA consortium addresses this research gap through a seven-step approach. First, transdiagnostic biosignatures of SCZ, BD and MDD are identified by GWAS and multi-modal omics signatures associated with treatment outcome and TR (steps 1 and 2). In a next step (step 3), a randomized controlled intervention study is conducted to test the efficacy and safety of an early intensified pharmacological treatment. Following this RCT, a combined clinical and omics-based algorithm will be developed to estimate the risk for TR. This algorithm-based tool will be designed for early detection and management of TR (step 4). This algorithm will then be implemented into a framework of shared treatment decision-making with a novel mental health board (step 5). The final focus of the project is based on patient empowerment, dissemination and education (step 6) as well as the development of a software for fast, effective and individualized treatment decisions (step 7). The project has the potential to change the current trial and error treatment approach towards an evidence-based individualized treatment setting that takes TR risk into account at an early stage.

The COVID-19 pandemic has a profound and lasting impact on the mental health of recovered individuals. To investigate the clinical risk factors associated with long-term post-traumatic stress symptoms (PTSS), anxiety, and depression in COVID-19 survivors, demographic information and medical records were collected during February 19 and March 20, 2020. Assessments of PTSS, anxiety, and depressive symptoms were conducted at two months (April to May 2020, Session 1) and two years (April to May 2022, Session 2) post-discharge. Session 1 included 127 survivors who were infected with the early strains of SARS-CoV-2, and 54 of these participants took part in Session 2. PTSS (median: Session 1 = 9, Session 2 = 7; p = 0.522) and depression (median: Session 1 = 5, Session 2 = 4; p = 0.127) remained unchanged over the two years following COVID-19 infection, while anxiety (median: Session 1 = 5, Session 2 = 2; p < 0.001) significantly decreased at the two-year mark. Severe COVID-19 symptoms were consistently identified as significant risk factors for depression at both time points (Session 1: dyspnea [beta = -0.268, p = 0.016], nausea or vomiting [beta = 0.239, p = 0.031]; Session 2: headache [beta = 0.414, p = 0.014]). They also emerged as risk factors for PTSS and anxiety at the two-month mark (PTSS: cough [beta = -0.334, p = 0.002]; anxiety: continued oxygen therapy [beta = 0.343, p = 0.002], cough [beta = -0.267, p = 0.013]). At the two-year mark, blood sample characteristics were identified as risk factors for PTSS (albumin: beta = 0.455, p = 0.010), anxiety (total bilirubin: beta = 0.440, p = 0.013), and depression (total bilirubin: beta = 0.386, p = 0.021). Mann-Whitney U-tests showed that female survivors had higher anxiety (p = 0.012) and depression (p = 0.046) levels than males at the two-month mark. The sample size was relatively small, and further investigation is needed to determine whether our findings can be directly applied to other samples, including those involving different variants of SARS-CoV-2. Our study may highlight the differences between short-term and long-term clinical risk factors for PTSS, anxiety, and depression in COVID-19 survivors. The identified predictors could provide valuable insights for tailoring interventions to improve the PTSS, anxiety, and depression outcomes at different stages of recovery in COVID-19 survivors.

Sex differences in schizophrenia have been noted across domains such as alexithymia and cognitive function; however, how they interact remains unclear. This study aimed to explore sex differences in the relationship between alexithymia and cognitive function in patients with chronic schizophrenia. A total of 695 patients (464 males and 231 females) who met the DSM-IV diagnostic criteria for schizophrenia were recruited in this cross-sectional study. Demographic and clinical data were collected using self-reported questionnaires. We assessed alexithymia using the Toronto Alexithymia Scale (TAS-20), cognitive function using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS). Male schizophrenic patients have to read 56.7% of the alexithymia rate, and higher scores on the RBANS visuospatial/constructional, language and total score than female patients (all P < 0.05).Alexithymia patients had lower language than non-alexithymia patients(P = 0.001). In addition, there were significant differences of the correlation scores for men and women in immediate memory and delayed memory (P < 0.001). Our results indicate that there are sex differences in the prevalence comorbid alexithymia symptoms, as well as their association with cognitive function, in patients with schizophrenia. However, a cross-sectional design could not establish definitive causative associations between sex and alexithymia or cognitive function.

Arketamine (R-ketamine), an enantiomer of ketamine, has historically been less studied than esketamine (S-ketamine) and the racemic mixture. Recent preclinical studies suggest that arketamine may offer prolonged antidepressant effects and a superior safety profile. This scoping review aims to assess and synthesise existing literature on the clinical use of arketamine in humans. This review follows the PRISMA for Scoping Reviews guidelines, with a comprehensive search conducted in PubMed, Embase, ClinicalTrials.gov, and the WHO International Clinical Trials Registry. Eligible studies included those reporting the administration of arketamine to humans. Data were extracted and synthesised descriptively. A total of 20 studies involving 410 subjects were included. Arketamine was primarily investigated for pain management and depression. While early evidence suggests arketamine may be effective in reducing pain, most studies were small and conducted in non-clinical settings. In psychiatry, trials indicate potential antidepressant effects, but results are inconsistent, and some studies remain unpublished. A consistent observation across most studies is arketamine's favourable safety profile, showing lower incidences of dissociative and psychotomimetic effects compared to esketamine and racemic ketamine. Arketamine may have a role in pain management and psychiatry, with a favourable safety profile compared to other forms of ketamine. However, the small scale of many studies limits the generalizability of findings, and results in depression trials are mixed. Larger, well-designed studies, possibly with higher doses, are needed to determine its therapeutic potential and establish its place in clinical practice.

The literature suggests that alterations in functional connectivity (FC) of the Salience Network (SN) may contribute to the manifestation of some clinical features of Autism Spectrum Disorder (ASD). The SN plays a key role in integrating external sensory information with internal emotional and bodily information. An atypical FC of this network could explain some symptomatic features of ASD such as difficulties in self-awareness and emotion processing and provide new insights into the neurobiological basis of autism. Using the Autism Brain Imaging Data Exchange II we investigated the resting-state FC of core regions of SN and its association with autism symptomatology in 29 individuals with ASD compared with 29 typically developing (TD) individuals. In ASD compared to TD individuals, seed-based connectivity analysis showed a reduced FC between the rostral prefrontal cortex and left cerebellum and an increased FC between the right supramarginal gyrus and the regions of the middle temporal gyrus and angular gyrus. Finally, we found that the clinical features of ASD are mainly associated with an atypical FC of the anterior insula and the involvement of dysfunctional mechanisms for emotional and social information processing. These findings expand the knowledge about the differences in the FC of SN between ASD and TD, highlighting atypical FC between structures that play key roles in social cognition and complex cognitive processes. Such anomalies could explain difficulties in processing salient stimuli, especially those of a socio-affective nature, with an impact on emotional and behavioral regulation.

The neural retina shares a common embryonic origin with the brain and yields pathological changes like that in the brain in various neuropsychiatric disorders, including schizophrenia. Non-invasive examination by optical coherence tomography (OCT) revealed retinal structure abnormalities in patients with schizophrenia. This study investigated retina structures in 29 patients with schizophrenia and 25 healthy controls in a Chinese Han ethnic population with spectral domain OCT. Measurements of central foveal thickness (CFT) as well as other retinal structures in macular and peripapillary subregions were performed. Associations between OCT parameters and clinical features, including severity of positive and negative symptoms, disease duration and antipsychotic dosage were analyzed. With controlling for age and sex, patients showed significantly thinner CFT, thinner central macular thickness, and thinner total retinal thickness in subregions of the central, inner superior, inner temporal, and inner nasal macula of both eyes, thinner ganglion cell complex in a subregion of the left eye, as well as larger cup volume in the peripapillary region of the right eye. In addition, CFT also negatively correlated with severity of negative symptoms. These findings suggest that CFT has the potential to be a disease biomarker of schizophrenia.

There is a lack of interventions that treat the Post-Covid-19 Condition (PCC) itself. Accordingly, treatment guidelines recommend physiotherapy interventions to alleviate symptoms and enhance functioning. In cases where unimodal treatments prove ineffective, non-organ-specific multidisciplinary bio-psycho-social rehabilitation (MBR) programs are a suitable option. In a pilot observational study with assessments at the entry and end of treatment we aimed to evaluate the feasibility of a 3-week day clinic MBR program and explore its effects on physical functioning in PCC patients with fatigue and reduced physical capacity. Patient selection was based on an interdisciplinary assessment involving a physician, a psychologist and a physiotherapist. Feasibility was determined based on full participation (≥ 8 of 9 days) and maintenance of stable endurance in the 6-Minute Walk Test (6MWT). From 37 patients included in the study, 33 completed the MBR (mean age: 43 ± 12 years, 73% female). Four patients discontinued the MBR, with two of them having reported deterioration of PCC symptoms. The 6MWT showed a numerical improvement from 501 ± 97 m to 512 ± 87 m, although it did not reach statistical significance. These results support the feasibility of outpatient MBR with a focus on active physiotherapy interventions in PCC patients with fatigue. This study aligns with previous research supporting the effectiveness of physiotherapy and rehabilitation in PCC patients. However, further research is needed to address possible different treatment responses and varying treatment approaches in subgroups of PCC patients.

Some people infected with SARS-CoV-2 report persisting symptoms following acute infection. If these persist for over three months, they are classified as post-COVID-19 syndrome (PCS). Although PCS is frequently reported, detailed longitudinal neuropsychological characterization remains scarce. We aimed to describe the trajectory of cognitive and neuropsychiatric PCS symptoms. 42 individuals with persisting cognitive deficits after asymptomatic to mild/moderate acute COVID-19 at study inclusion received neuropsychological assessment at baseline (BL) and follow-up (FU; six months after BL). Assessments included comprehensive testing of five neurocognitive domains, two cognitive screening tests, and questionnaires on depression, anxiety, sleep, fatigue, and health-related quality of life. Results showed high rates of subjective cognitive complaints at BL and FU (95.2% versus 88.1%) without significant change over time. However, objectively measured neurocognitive disorder (NCD) decreased (61.9% versus 42.9%). All cognitive domains were affected, yet most deficits were found in learning and memory, followed by executive functions, complex attention, language, and perceptual motor functions. In individuals with NCD, the first three domains mentioned improved significantly over time, while the last two domains remained unchanged. Cognitive screening tests did not prove valuable in detecting impairment. Neuropsychiatric symptoms remained constant except for quality of life, which improved. This study emphasizes the importance of comprehensive neuropsychological assessment in longitudinal research and provides valuable insights into the trajectory of long-term neuropsychological impairments in PCS. While cognitive performance significantly improved in many domains, neuropsychiatric symptoms remained unchanged.