Acta Neuropsychiatrica最新文献

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.

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, and variations in CYP2D6 activity may affect treatment response or adverse effects. However, the impact of these variations on adherence and medication attitudes is unclear. This study investigates the relationships between CYP2D6 phenotype, self-reported adherence, adverse effects, and attitudes among aripiprazole and risperidone users. The study analysed 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 analysed using logistic regression and beta regression in aripiprazole and risperidone groups separately. Among risperidone users, we observed no association between CYP2D6 phenotypes and adherence, adverse effects, or attitudes. Similarly, we found no link 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 favourable attitudes towards antipsychotic treatment (β = −0.48, p = 0.023). These findings provide 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.

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.

Objective: New developments in neuro-navigation and machine learning have allowed for personalised approaches to repetitive transcranial magnetic stimulation (rTMS) to treat various neuropsychiatric disorders. One specific approach, known as the cingulum framework, identifies individualised 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 are unclear.

Methods: We performed a retrospective study on 165 unique patients (202 target sets) treated with this personalised approach between January 2020 and 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 individualised, connectome-guided rTMS is safe and contain side-effect profiles similar to other TMS approaches reported in the literature.

Aim: Mild behavioural 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 standardised 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.

Objectives: Selective serotonin reuptake inhibitors (SSRIs) have been associated with increased risk of osteoporosis, and sertraline may be more potent than citalopram in this regard. Here, target trial emulation was used to investigate whether sertraline, citalopram and escitalopram (the S-enantiomer of citalopram) differentially affect the risk of osteoporosis. Subsequently, it was examined whether SSRIs increase the risk of osteoporosis in a dose-response-like manner.

Methods: Danish nationwide registers were used to identify all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram between January 1, 2007, and March 1, 2019. These individuals were followed until development of osteoporosis, death, or end of follow-up. Cox proportional hazards regression was used to adjust for relevant baseline covariates to emulate randomised treatment allocation to compare the rate of osteoporosis for individuals treated with sertraline, citalopram or escitalopram. Subsequently, the cumulative dose of sertraline, citalopram, and escitalopram was calculated, and Cox proportional hazards regression was used to assess dose-response-like relationships with osteoporosis.

Results: We identified 27,280, 65,529, and 17,703 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. There was no material or statistically significant differential risk of osteoporosis between these groups (adjusted hazard rate ratio, aHRR = 0.98 for citalopram versus sertraline and aHRR = 0.94 for escitalopram versus sertraline). The results were not indicative of the SSRIs having a dose-response-like effect on osteoporosis risk.

Conclusions: Sertraline, citalopram and escitalopram do not appear to differentially affect the risk of osteoporosis. The lack of clear dose-response-like relationships suggest that they do not have a causal effect on osteoporosis risk.

Major depressive disorder (MDD) is considered a psychiatric disorder and have a relationship with stressful events. Although the common therapeutic approaches against MDD are diverse, a large number of patients do not present an adequate response to antidepressant treatments. On the other hand, effective non-pharmacological treatments for MDD and their tolerability are addressed. Several affective treatments for MDD are used but non-pharmacological strategies for decreasing the common depression-related drugs side effects have been focused recently. However, the potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs), microRNAs (miRNAs) as cell-based therapeutic paradigms, besides other non-pharmacological strategies including mitochondrial transfer, plasma, transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and exercise therapy needs to further study. This review explores the therapeutic potential of cell-based therapeutic non-pharmacological paradigms for MDD treatment. In addition, plasma therapy, mitotherapy, and exercise therapy in several in vitro and in vivo conditions in experimental disease models along with tDCS and TMS will be discussed as novel non-pharmacological promising therapeutic approaches.

Introduction: Extant literature implicates the role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) on modulating alcohol-associated behaviours, with a particular emphasis of these agents on neural circuits subserving reward and appetite control. Herein, we explore the potential effects of GLP-1RAs on alcohol-associated behaviours in brain regions implicated in reward processing facilitating the repurposing of these agents for the treatment and prevention of problematic drinking. Understanding how GLP-1's analogues interact with alcohol-related behaviours may underscore the development of therapeutic strategies for alcohol use disorder (AUD) and those with comorbid metabolic disorders.

Methods: A systematic review was conducted, wherein relevant literature was identified through Web of Science, PubMed, and OVID (MedLINE, Embase, AMED, PsycInfo, JBI EBP) from database inception to October 27th, 2024. Preclinical and clinical studies examining the association between GLP-1RAs and alcohol-related behaviours were assessed.

Results: Preclinical studies (n = 19) indicate that GLP-1RAs attenuate alcohol-related behaviours, with exenatide demonstrating significant dose-dependent effects in high alcohol-consuming phenotypes. Semaglutide and liraglutide are associated with reduced alcohol intake, though their effects were often transient. In human studies (n = 2) with AUD, semaglutide significantly reduced alcohol consumption, while exenatide showed mixed results, with reductions in alcohol drinking within high BMI subpopulations.

Discussion: Extant preclinical and clinical literature provides preliminary support for the potential therapeutic role of GLP-1RAs in attenuating alcohol consumption and preference. There is a need for large well controlled studies evaluating the effect of GLP-1RAs as a treatment strategy for behavioural modifications in individuals living with alcohol use disorder.

Objective: Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroproliferative effects and modulatory effects in neuronal pathways. Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on neurogenesis.

Methods: We examined studies that investigate changes in neurogenesis mediated by GLP-1 and GLP-1 RA administration in both human and animal populations. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to July 2nd. Primary studies investigating the role of GLP-1 and GLP-1 RAs on neurogenesis were included for analysis.

Results: GLP-1 and GLP-1 RAs (i.e. exenatide, geniposide, liraglutide, lixisenatide, and semaglutide), increased neurogenesis within the dentate gyrus, hippocampus, olfactory bulb, and the medial striatum in animal models. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in multiple apoptotic pathways and upregulating survival pathways.

Discussion: GLP-1 and GLP-1 RAs are positively associated with neurogenesis. This effect may have translational implications insofar as disparate mental disorders that are characterised by neurogenesis defects (e.g. depressive disorders and neurocognitive disorders) may be benefitted by these agents.