Acta Neuropsychiatrica最新文献

Objective: Compulsive-like rigidity may be associated with hyposerotonergia and increased kynurenine (KYN) pathway activity. Conversion of tryptophan (TRP) to kynurenine (KYN), which may contribute to hyposerotonergia, is bolstered by inflammation, and could be related to altered gut microbiota composition. Here, we studied these mechanisms in a naturalistic animal model of compulsive-like behavioural rigidity, i.e., large nest building (LNB) in deer mice (Peromyscus sp.).

Methods: Twenty-four (24) normal nest building (NNB)- and 24 LNB mice (both sexes) were chronically administered either escitalopram (a selective serotonin reuptake inhibitor; 50 mg/kg/day) or a control solution, with nesting behaviour analysed before and after intervention. After endpoint euthanising, frontal cortices and striata were analysed for TRP and its metabolites, plasma for microbiota derived lipopolysaccharide (LPS) and its binding protein (LBP), and stool samples for microbial DNA.

Results: LNB, but not NNB, decreased after escitalopram exposure. At baseline, LNB associated with reduced frontal cortical TRP concentrations and hyposerotonergia that was unrelated to altered KYN pathway activity. In LNB mice, escitalopram significantly increased frontal-cortical and striatal TRP without altering serotonin concentrations. Treated LNB, compared to untreated LNB- and treated NNB mice, had significantly reduced plasma LPS as well as a microbiome showing a decreased inferred potential to synthesise short-chain fatty acids and degrade TRP.

Conclusion: These findings support the role of altered serotonergic mechanisms, inflammatory processes, and gut microbiome involvement in compulsive-like behavioural rigidity. Our results also highlight the importance of gut-brain crosstalk mechanisms at the level of TRP metabolism in the spontaneous development of such behaviour.

Objective: Suicidality is a significant public health concern, with neuroimaging studies revealing abnormalities in the brains of suicidal individuals and post-mortem samples. However, the genetic architecture between suicidality and subcortical brain volumes remains poorly characterized. Using Genome-Wide Association Studies (GWAS), we investigated the genetic overlap between suicidality and subcortical brain volume.

Methods: GWAS summary statistics for suicidal behaviours, including Suicide Attempts, Ever Self-Harmed, and Thoughts of Life Not Worth Living, from the UK Biobank, Suicide from the FinnGen Biobank, and data on seven subcortical brain volumes and Intracranial Volume from the ENIGMA2 study, were used to investigate the genetic correlation between phenotypes as well as potential genetic factors.

Results: A common genetic factor was identified, comprising two categories: Suicide Attempt, Ever Self-Harmed, and Thoughts of Life Not Worth Living from the UK Biobank, and Suicide from FinnGen, Intracranial Volume, and subcortical brain volumes. Cross-phenotype GWAS meta-analysis of each category at variant, gene and subnetwork levels unveils a list of significant variants (P-value < 5 × 10^-8), and potential hub genes (P-value < 0.05) of consideration. Network, pathway, and Gene Ontology analyses of these joint categories highlighted enriched pathways and biological processes related to blood-brain barrier permeability suggesting that the presence and severity of suicidality are associated with an inflammatory signature detectable in both blood and brain tissues.

Conclusion: This study underscores the role of brain and peripheral blood inflammation in suicide risk and holds promise for developing targeted interventions and personalized treatment strategies to reduce suicidality in at-risk populations.

Objective: This study focused on the effect of the cognitive behavioral therapy (CBT) combined with aripiprazole on cognitive functions and psychological state of schizophrenia patients.

Method: Seventy-eight schizophrenia patients were divided into two groups. One group received aripiprazole with conventional nursing treatment for 3 months (control group, n = 39), and the other received aripiprazole with CBT for 3 months (observation group, n = 39) (1 session per week, each session lasting 60 minutes. In the two groups before and after treatment, the severity of symptoms was evaluated using the Psychiatric Symptom Rating Scale (BPRS). Cognitive function was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Positive and Negative Symptom Scale (PANSS) was utilized to evaluate mental status, while the Generalized Self-Efficacy Scale (GSES) measured psychological state. Additionally, the quality of life was assessed using the General Quality of Life Inventory-74 (GQOLI-74). In the final analysis, post-treatment efficacy and complications for the two groups were counted.

Results: Both groups showed significant improvements: BPRS and PANSS scores decreased, while RBANS, GSES, and GQOLI-74 scores increased. The observation group showed greater improvements than the control group. The total improvement rate was 89.74% (35/39) in the observation group, higher than the 71.79% (28/39) in the control group. The complication rate was 33.33% (13/39) in the observation group and 38.46% (15/39) in the control group.

Conclusion: The treatment of CBT combined with aripiprazole for schizophrenia has a significantly positive effect on the cognitive functions and psychological state of patients.

Objectives: Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD) are collectively called as Lewy body dementia (LBD). Despite the urgent clinical need, there is no reliable protein biomarker for LBD. Hence, we conducted the first comprehensive systematic review of all Differentially Abundant Proteins (DAP) in all tissues from people with LBD for advancing our understanding of LBD molecular pathology that is essential for facilitating discovery of novel diagnostic biomarkers and therapeutic targets for LBD.

Methods: We identified eligible studies by comprehensively searching five databases and grey literature (PROSPERO protocol:CRD42020218889). We completed quality assessment and extracted relevant data. We completed narrative synthesis and appropriate meta-analyses. We analysed functional implications of all reported DAP using DAVID tools.

Results: We screened 11,006 articles and identified 193 eligible studies. 305 DAP were reported and 16 were replicated in DLB. 37 DAP were reported and three were replicated in PDD. Our meta-analyses confirmed six DAP (TAU, SYUA, NFL, CHI3L1, GFAP, CLAT) in DLB, and three DAP (TAU, SYUA, NFL) in PDD. There was no replicated blood-based DAP in DLB or PDD. The reported DAP may contribute to LBD pathology by impacting misfolded protein clearance, dopamine neurotransmission, apoptosis, neuroinflammation, synaptic plasticity and extracellular vesicles.

Conclusion: Our meta-analyses confirmed significantly lower CSF TAU levels in DLB and CSF SYUA levels in PDD, when compared to Alzheimer's disease. Our findings indicate promising diagnostic biomarkers for LBD and may help prioritising molecular pathways for therapeutic target discovery. We highlight ten future research priorities based on our findings.

Background: Neuropsychiatric disorders in preeclampsia (PE) women are prevalent and worsen PE outcome. Immune-related biomarkers including soluble sCD80 and cytotoxic T-lymphocyte antigen-4 (sCTLA-4) are not well studied in relation to depression, anxiety, and chronic fatigue due to PE.

Methods: The aim is to study serum immune-inflammatory biomarkers of PE and delineate their associations with the Hamilton Depression (HAMD), Anxiety (HAMA), and Fibro-Fatigue (FF) rating Scale scores. sCD80, sCTLA-4, vitamin D, granulocyte-macrophage colony-stimulating factor, zinc, copper, magnesium, and calcium were measured in 90 PE compared with 60 non-PE pregnant women.

Results: PE women show higher depression, anxiety and FF rating scale scores as compared with control women. sCTLA-4, sCD80, and copper were significantly higher and zinc, magnesium, and calcium significantly lower in PE women than in controls. Multiple regression analysis showed that around 55.8%-58.0% of the variance in the HAMD, HAMA and FF scores was explained by the regression on biomarkers; the top 3 most important biomarkers were sCTLA-4, sCD80, and vitamin D. The sCTLA-4/sCD80 ratio was significantly and inversely associated with the HAMD/HAMA/FF scores. We found that around 70% of the variance in systolic blood pressure could be explained by sCTLA-4, vitamin D, calcium, and copper.

Conclusions: The findings underscore that PE and depression, anxiety, and chronic fatigue symptoms due to PE are accompanied by activation of the immune-inflammatory response system. More specifically, disbalances among soluble checkpoint molecules seem to be involved in the pathophysiology of hypertension and neuropsychiatric symptoms due to PE.

Background: Non-adherence and negative attitudes towards medication are major problems in treating psychotic disorders. Cytochrome P450 2D6 (CYP2D6) contributes to the metabolism of aripiprazole and risperidone. Variations in CYP2D6 activity may affect treatment response or adverse effects. The impact of these variations on adherence and medication attitudes is unclear.

Aims: This study investigates the relationships between CYP2D6 phenotype, self-reported adherence, adverse effects, and attitudes among aripiprazole and risperidone users.

Methods: This study analyzed data from the SUPER-Finland cohort of 10,474 adults with psychotic episodes, including 1,429 aripiprazole and 828 risperidone users. The Attitudes towards neuroleptic treatment (ANT) questionnaire assessed adherence and adverse effects in all patients, while medication-related attitudes were examined in a subgroup of 1,000 participants. Associations between CYP2D6 phenotypes and outcomes were analyzed using logistic regression and beta regression in aripiprazole and risperidone groups separately.

Results: Among risperidone users, we observed no association between CYP2D6 phenotypes and adherence, adverse effects, or attitudes. Similarly, no link was found between adherence and CYP2D6 phenotypes among aripiprazole users. However, aripiprazole users with the ultrarapid CYP2D6 phenotype had more adverse effects (OR = 1.71, 95 % CI 1.03-2.90, p = 0.041). Among aripiprazole users, CYP2D6 ultrarapid phenotype was associated with less favorable attitudes towards antipsychotic treatment (β = -0.48, p = 0.023).

Conclusions: We found preliminary evidence that the ultrarapid CYP2D6 phenotype is associated with increased adverse effects and negative attitudes towards antipsychotic medication among aripiprazole users. CYP2D6 phenotype did not influence adherence, adverse effects, or attitudes among risperidone users.

Growing evidence suggests that psychedelic-assisted therapies can alleviate depression, anxiety, posttraumatic stress, and substance use disorder, offering relatively safe profiles, enhanced efficacy, and lasting effects after a few applications. Athletes often experience high levels of stress and pressure, making them susceptible to these psychiatric conditions. However, the effects of psychedelic substances on athletic performance remain largely unknown. Before potential acceptance, evaluating their impact on physical and physiological measures beyond mental health outcomes is crucial. Here, we aim to explore this topic and highlight research directions to advance our understanding. Preclinical studies suggest that psilocybin/psilocin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and ayahuasca possess anti-inflammatory and anti-nociceptive properties. Studies investigating the effects of classical psychedelics or 3,4-methylenedioxymethamphetamine (MDMA) on factors such as muscle strength, motor coordination, locomotion, endurance, fluid and electrolyte balance, hormonal regulation, and metabolism are still scarce. While adhering to regulatory frameworks, further research in animal models, athletes, and non-athletes is needed to address these gaps, compare psychedelics with commonly used psychoactive drugs, and explore the potential prophylactic and regenerative benefits of specific interventions.

Objective: New developments in neuro-navigation and machine learning have allowed for personalized approaches to repetitive transcranial magnetic stimulation (rTMS) to treat various neuropsychiatric disorders. One specific approach, known as the Cingulum Framework, identifies individualized brain parcellations from resting state fMRI based on a machine-learning algorithm. Theta burst stimulation, a more rapid form of rTMS, is then delivered for 25 sessions, 5 per day, over 5 days consecutively or spaced out over 10 days. Preliminary studies have documented this approach for various neurological and psychiatric ailments. However, the safety and tolerability of this approach is unclear.

Methods: We performed a retrospective study on 165 unique patients (202 Target Sets) treated with this personalized approach between January 2020 to December 2023.

Results: Common side effects included fatigue (102/202, 50%), local muscle twitching (89/202, 43%), headaches (49/202, 23%), and discomfort (31/202, 17%), all transient. The top 10 unique parcellations commonly found in the Target Sets included L8av (52%), LPGs (28%), LTe1m (21%), RTe1m (18%), LPFM (17%), Ls6-8 (13%), Rs6-8 (9%), L46 (7%), L1 (6%), and L6v (6%). Fatigue was most common in Target Sets that contained R6v (6/6, 100%) and L8c (5/5, 100%). Muscle twitches were most common in Target Sets that contained RTGv (5/5, 100%) and LTGv (4/4, 100%).

Conclusion: These side effects were all transient and well-tolerated. No serious side effects were recorded. Results suggested that individualized, connectome-guided rTMS is safe and contain side effect profiles similar to other TMS approaches reported in the literature.

Major depressive disorder (MDD) and coronary heart disease (CHD) can both cause significant morbidity and mortality. The association of MDD and CHD has long been identified, but the mechanisms still require further investigation. Seven mRNA microarray datasets containing samples from patients with MDD and CHD were downloaded from Gene Expression Omnibus. Combined matrixes of MDD and CAD were constructed for subsequent analysis. Differentially expressed genes (DEGs) were identified. Functional enrichment analyses based on shared DEGs were conducted to identify pivotal pathways. A protein-protein network was also applied to further investigate the functional interaction. Results showed that 24 overlapping genes were identified. Enrichment analysis indicated that the shared genes are mainly associated with immune function and ribosome biogenesis. The functional interactions of shared genes were also demonstrated by PPI network analysis. In addition, three hub genes including MMP9, S100A8, and RETN were identified. Our results indicate that MDD and CHD have a genetic association. Genes relevant to immune function, especially IL-17 signalling pathway may be involved in the pathogenesis of MDD and CHD.

Aim: Mild behavioral impairment (MBI) is a neurobehavioral prodrome to dementia with multiple phenotypic characteristics. To investigate the complex neurobiological substrate underlying MBI, we evaluated its association with a composite magnetic resonance imaging (MRI)-based measure of concomitant cerebrovascular disease (CeVD) and neurodegeneration; and the interaction effects of MBI and MRI scores on cognitive and clinical trajectory.

Methods: 253 dementia-free participants (mean age=71.9, follow-up period=49.89 months) from 2 memory clinics were included in this study. 37 (14.6%) participants met clinical diagnostic criteria for MBI, ascertained by repeated neuropsychiatric inventory assessments. MRI scores were computed using a validated weighted sum of white matter hyperintensities volume, presence of infarct, hippocampal volume, and cortical thickness of known Alzheimer's disease-associated regions. Clinical and cognitive outcomes were evaluated annually using the Clinical Dementia Rating sum-of-boxes (CDR-SB) and standardized global cognitive scores of a comprehensive neuropsychological battery respectively.

Results: Lower MRI scores, indicating greater burden of comorbid CeVD and neurodegeneration, yielded a 3.8-fold likelihood of MBI compared to 1.5-fold with larger WMH volume or lower cortical thickness individually. Interaction analyses showed that MBI participants with low MRI scores had greater increase in CDR-SB (B=0.05, SE=0.01, p<0.001) over time. All models involving the composite MRI measure yielded a better fit compared to reduced models with either pathology alone.

Conclusion: MBI is associated with a composite MRI measure that reflects mixed pathologies of dementia and their co-evaluation may improve risk profiling and identification of memory clinic patients without dementia who are at the highest risk of experiencing clinical decline.