Acta Neuropsychiatrica最新文献

The 22q11.2 deletion syndrome (22q11DS) is a genetic disorder characterised by defined microdeletions at chromosome 22q11.2. These genetic changes lead to a variety of neurodevelopmental problems, including cognitive delays and a very high rate of symptoms on the autism and schizophrenia spectrum. The underlying mechanisms contributing to these neurodevelopmental manifestations remain poorly understood. In concert with these neurodevelopmental difficulties there are also immune system alterations, including autoimmunity. We hypothesise that immune dysfunction and the presence of circulating autoantibodies may play a role in the pathophysiology of these neuropsychiatric symptoms. In this review, we synthesise the diverse literature on autoantibodies in 22q11DS and propose mechanisms for a causative role of these autoantibodies in neurobehavioural problems such as psychosis and cognitive delays. This review highlights the importance of further research to explore the interaction between autoreactive antibodies and functional alterations in neurocircuitry function. Understanding this relationship may provide insight into the origins of psychiatric symptoms.

Background: There is no recognised cure or specific biomarker for autism spectrum disorder (ASD). Exosomes are small vesicles that carry proteins, lipids and nucleic acids. They have been investigated for diseases such as Parkinson’s and Alzheimer’s. As the conclusions were on the biological utility of exosomes as a non-invasive brain biopsy, some animal, human and in vitro exosome studies have also been presented in the ASD field. The purpose of this review is to compile the studies that have established a relationship between ASD and exosomes so far and discuss their potential for linking the gap between the laboratory and clinic.

Methods: In this systematic review, 31 PubMed articles were identified using the keywords ‘exosomal’, ‘exosome and ‘autism spectrum disorder’. After excluding 16 reviews, 4 irrelevant studies and 1 preprint, and adding 5 relevant articles, 15 research articles were included based on PRISMA criteria. The articles were investigated and reviewed by both authors. Their methodology and results are also discussed according to two main streams in studies.

Results: Numerous studies have identified potential biomarkers, including mitochondrial DNA (mtDNA7S), cytokines including IL-1β, TNF-α and IL-6, and different types of RNAs by comparing the exosomal contents of ASD patients or models with controls. In studies that focused on treatment, behavioural improvements were shown in ASD model mice.

Conclusion: Since there are presently no reliable biomarkers or effective treatments for ASD, exosome-based research offers a promising avenue for early diagnosis and the creation of tailored therapies.

Background: Contrary to the negative acute-phase protein (APP) response, there is no consistent correlation between serum pentameric C-reactive protein (pCRP) and major depression (MDD). Monomeric CRP (mCRP), a dissociation product of pCRP under immune-inflammatory conditions, exhibits pro-inflammatory effects; however, it has not been investigated in MDD or its subtypes, major dysmood disorder (MDMD) and simple dysmood disorder (SDMD).

Objective: To examine serum mCRP, albumin, transferrin, M1 macrophage and Thelper-17 immune profiles, and adverse childhood experiences (ACEs) in MDD, MDMD and SDMD.

Methods: Seventy-nine MDMD patients, 30 SDMD patients, and 40 controls were included. Serum mCRP was measured by ELISA; albumin, transferrin, and pCRP by biochemical assays; and cytokines using Luminex technology.

Results: MDMD patients showed significantly higher mCRP compared with SDMD and controls, while both patient groups exhibited reduced albumin and transferrin. Combining mCRP with albumin and transferrin showed an adequate accuracy for MDD (area under the ROC Curve = 0.793). Adding IL-17A and ACEs improved accuracy (ROC = 0.855). Serum mCRP levels are additionally associated with pCRP, M1 macrophage profile, body mass index, and ACEs. Up to 36.6% of the variance in overall severity of depression was explained by mCRP, T-helper-17 profile, ACEs (all positively), albumin and transferrin (both inversely).

Conclusion: Future research in MDD should employ mCRP rather than pCRP as a biomarker of depression/MDMD. Combining mCRP with biomarkers of the negative acute-phase response identified 63.7% of MDD patients with a smouldering acute-phase response, with a specificity of 82.1%. We recommend to assess mCRP rather than pCRP in MDD studies.

In basic neuropsychopharmacological research, some biobehavioural phenomena — e.g., population migration and navigation over long distances — are rarely considered because the most commonly used laboratory animals show little or no evidence of these phenomena. Nevertheless, they can be also relevant for the mechanism of human psychic aberrations. An annual migration is seen in migratory birds, certain marine mammals and several ungulates. For migratory birds, the time of departure is determined by the length of the photoperiod and is much less changeable than the chosen route. When navigating, migratory birds also use the direction and strength of the field lines of the Earth’s magnetic field. Because humans also seem to exhibit a certain sensitivity to the Earth’s magnetic field, the regulation in birds could also provide hints for research on human well-being. Some bird species have such highly developed cognitive abilities that this is considered proof of the possession of consciousness. Therefore, some birds may be suitable as experimental animals in neurobiological models for cognitive functions and for making the world of thought accessible. The dorsal diencephalic conduction system (DDCS) in humans is difficult to study due to its small size and complex architecture, but it is relatively well developed in more primitive vertebrates. For research into the primary interactions between the DDCS and the rest of the brain, the lamprey can be used as laboratory animal. There is manifold evidence that the DDCS along with forebrain and upper brainstem is of functional relevance and the significance of the DDCS in cortical-controlled networks could then be investigated in birds and verified in humans.

Background: Motor functional neurological disorder (FND) is a common illness associated with significant functional impairment. There are no effective pharmacotherapies, and despite the early promise of physiotherapy studies, many suffer disabling symptoms in the long term. There is a theoretical rationale for combining psychedelics with physiotherapy; however, the potential benefit of this approach and optimal treatment model remains unexplored. Here, we present the protocol for the first study investigating the tolerability, feasibility, and potential efficacy of two distinct treatment regimens of psilocybin-assisted physiotherapy for refractory motor FND: a moderate dose that incorporates movement tasks during the acute drug effects versus a standard dose alone.

Methods: Twenty-four participants with refractory motor FND will be randomised in a 1:1 ratio to either (1) psilocybin 15 mg, with movement tasks conducted during the acute drug effects, or (2) psilocybin 25 mg alone. All participants will receive two sessions of FND-specific physiotherapy pre-dosing, six sessions of physiotherapy post-dosing, and undergo follow-up visits one week and four weeks following their final physiotherapy session. A battery of outcome measures will be completed as scheduled, assessing tolerability, feasibility, motor FND symptom severity, psychiatric and physical symptoms, quality of life, treatment expectations, intensity of the acute drug effects, personality, motor function, force-matching performance, resting-state and task-based brain imaging, and subjective experiences of the study treatment.

Discussion: These findings will assist the design of an adequately powered randomised controlled trial in this cohort. The findings may also inform the feasibility of psychedelic treatment in related functional and neuropsychiatric disorders.

Objective: Structural abnormalities in cortical and subcortical brain regions are consistently observed in schizophrenia; however, substantial inter-individual variability complicates identifying clear neurobiological biomarkers. The Person-Based Similarity Index (PBSI) quantifies individual structural variability; however, its applicability across schizophrenia stages remains unclear. This study aimed to compare cortical and subcortical structural variability in recent-onset and chronic schizophrenia and explore associations with clinical measures.

Methods: Neuroimaging data from 41 patients with recent-onset schizophrenia, 32 with chronic schizophrenia, and 59 healthy controls were analysed. The PBSI scores were calculated for cortical thickness, surface area, cortical grey matter volume, and subcortical volumes. Group differences in PBSI scores were assessed using linear regression and analysis of variance. Correlations between the PBSI scores and clinical measures were also examined.

Results: Both patients with recent-onset and chronic schizophrenia exhibited significantly lower PBSI scores than healthy controls, indicating greater morphometric heterogeneity. However, significant differences between the recent-onset and chronic patient groups were limited to subcortical and cortical thickness PBSI scores. Correlations between PBSI scores and clinical symptoms are sparse and primarily restricted to surface area variability and symptom severity in patients with recent-onset schizophrenia.

Conclusion: Patients with schizophrenia show marked structural brain heterogeneity compared with healthy controls, which is detectable even in the early stages of the illness. Although there were few differences in PBSI scores between the recent-onset and chronic schizophrenia groups and limited correlations between PBSI scores and clinical measures, the PBSI may still provide valuable insights into individual differences contributing to clinical heterogeneity in schizophrenia.

Objective: To assess satisfaction and pain-related knowledge levels following an inclusive Pain Neuroscience Education (PNE) programme in improving pain-related knowledge and perceived satisfaction among adolescents with and without intellectual disabilities, and to assess its applicability in digital health education settings. Methods: A multicentre, cross-sectional study was conducted in 15 public schools. A total of 373 students (5th-6th grade), including those with intellectual disabilities, participated in a hybrid-format PNE programme delivered in two 90-minute sessions. Satisfaction and knowledge were assessed using an adapted, easy-to-read questionnaire, with exploratory factor analysis identifying three core domains: activity format, teacher evaluation, and SDG-related training. Results: Overall satisfaction and knowledge gains were high across all participants. No significant differences were found between students with and without intellectual disabilities or between urban and rural schools in satisfaction and teacher evaluation. However, rural students reported greater awareness of the SDG-related content (p < 0.05). Conclusion: The adapted PNE programme was well-received and associated with high levels of pain-related knowledge across diverse educational contexts. Its inclusive and hybrid design supports its potential scalability through digital health strategies, promoting equity in pain education.

Introduction: Autoimmune psychosis (AP) and other autoimmune psychiatric syndromes (APS) are associated with central nervous system antibodies. This study investigated related magnetic resonance spectroscopic imaging (MRSI) signatures and their correlations with electroencephalography (EEG), cerebrospinal fluid (CSF), and psychometric/neuropsychological measures.

Methods: Twenty-eight adults with suspected antibody-positive AP spectrum syndromes were compared with 28 matched healthy controls. Inclusion in the patient group was based on the APS concept, resulting in a heterogeneous group with uniform autoimmunity. MRSI was performed using a spiral-encoded Mescher-Garwood localised adiabatic selective refocusing 3D-MRSI sequence. Glutamate+glutamine (Glx), gamma-aminobutyric acid (GABA), total N-acetylaspartate (tNAA), and total creatine (tCr) were reported as ratios to tNAA and/or tCr. EEG was analysed for intermittent rhythmic delta/theta activity (IRDA/IRTA) using independent component analysis.

Results: No significant differences in Glx, GABA, tNAA, or tCr ratios were observed between patients and controls. Correlation analyses in patients showed a trend for a negative association of the IRDA/IRTA rate before hyperventilation with the GABA/tCr ratio in both hippocampi and with the GABA/tNAA ratio in the left hippocampus and Glx/tCr ratio in the right putamen and pallidum. Significant positive correlations were observed between inflammatory CSF markers (white blood cell count and IgG Index) and GABA/tCr and GABA/tNAA ratios in the left caudate nucleus and right isthmus cingulate and thalamus, as well as between negative symptoms in PANSS and higher GABA/tCr ratios in the right putamen.

Discussion: No group differences were identified; however, correlations suggest a link between neuroinflammatory CSF markers and negative symptoms with GABAergic signalling in patients. Multimodal diagnostic approaches may provide a better understanding of the link between neuroinflammation, neurochemistry, and EEG slowing.

Objective: Amisulpride, a substituted benzamide derivative, has a unique pharmacological profile characterised by a high affinity for dopaminergic D₂/D₃ receptors, as well as an affinity for 5-HT₇ receptors. Its effectiveness and safety surpass those of traditional antipsychotic drugs and multi-receptor antipsychotic medications in improving global symptoms, including both positive and negative symptoms. This makes it a compelling subject for study. However, the molecular mechanisms that contribute to its clinical efficacy in treating schizophrenia remain largely unexplored.

Methods: We assessed cell viability following amisulpride treatment using the MTT and a real-time cell viability assay. Subsequently, we conducted RNA-seq and LC-MS/MS analyses to identify differentially expressed genes and proteins in SH-SY5Y neuroblastoma cells treated with amisulpride.

Results: In the present study, we used RNA-seq analysis to identify downregulated expression of a transcriptional factor, FOSB, in amisulpride-treated SH-SY5Y neuroblastoma cells, while using LC-MS/MS analysis to identify multiple differentially expressed proteins in these cells. Among these differentially expressed proteins, we confirmed four proteins (ACTG1, ANP32E, CLTC, IPO8) that are differentially expressed under the administration of amisulpride.

Conclusion: Our data reveal novel insights into the role of amisulpride in modulating the differential expression of genes and proteins. These findings, which involve genes/proteins related to AP-1 transcription factor family gene regulation, cytoskeleton, histone binding activity, the intracellular trafficking of receptors and endocytosis of a variety of macromolecules, and nuclear localisation signal, are particularly significant as they shed light on the molecular underpinnings of the clinical efficacy of amisulpride and the pathogenesis of schizophrenia.

Progress in the development of new and improved medications for psychosis has been notably slow and disappointing. The first treatment for schizophrenia was introduced in early 1950s and the majority of medications available today exclusively function through dopamine antagonism. The search for a new drug treatment with a different mechanism of action was extremely slow-paced mainly due to the limited understanding of the aetiology, pathophysiology and genetics of schizophrenia. Given the fact that a third of people do not respond to dopamine antagonists, there is a clear need for an antipsychotic with a different mechanism of action. In 2024, FDA approved a new medication for psychosis branded as Cobenfy. This xanomeline-trospium combination works via cholinergic pathway and the dual M1 and M4 receptor activation helps regulates dopaminergic and glutaminergic neurotransmission as well, thereby restoring balance in these circuits. Acetylcholine also helps improve cognitive processing including attention, learning and sensory gating. In this article, we try to understand the place of this unique drug in the antipsychotic ladder. We also explore the clinical scenarios where this medication can be effective as well as the potential future outlook when it comes to the treatment of schizophrenia.