Acta Neuropsychiatrica最新文献

Introduction: Extant literature indicated that glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may potentially reduce risk of opioid overdose in persons with opioid use disorders (OUDs). Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on OUDs.

Methods: We examined preclinical and clinical paradigms examining the effects of GLP-1 and GLP-1 RAs on OUD and OUD-associated behaviours (i.e. opioid self-administration, opioid-seeking behaviour). Relevant articles were retrieved from OVID (MedLine, Embase, AMED, PsychINFO, and JBI EBP Database), PubMed, and Web of Science from database inception to 1 May 2025. Primary studies (n = 10) examining the aforementioned effects associated with GLP-1 and GLP-1 RA administration were retrieved for analysis.

Results: GLP-1 RAs (i.e. exenatide, liraglutide) reduced opioid-seeking behaviour (p < 0.05) and self-administration of opioid drugs (p < 0.05) in preclinical paradigms. In addition, results from human studies indicate that GLP-1 administration was associated with reducing the risk of opioid overdose in human studies (aIRR = 0.60, 95% CI [0.43, 0.83]).

Conclusion: GLP-1 RAs may affect opioid self-administration as well as the risk for overdose as evidenced by both preclinical and clinical data. There is a need for adequate well-controlled studies to determine whether GLP-1 RAs may provide clinically meaningful improvement and risk reduction in persons living with OUDs.

Objective: Cortisol is a well-established biomarker of stress, assessed through salivary or blood samples, which are intrusive and time-consuming. Speech, influenced by physiological stress responses, offers a promising non-invasive, real-time alternative for stress detection. This study examined relationships between speech features, state anger, and salivary cortisol using a validated stress-induction paradigm.

Methods: Participants (N = 82) were assigned to cold (n = 43) or warm water (n = 39) groups. Saliva samples and speech recordings were collected before and 20 minutes after the Socially Evaluated Cold Pressor Test (SECPT), alongside State-Trait Anger Expression Inventory (STAXI) ratings. Acoustic features from frequency, energy, spectral, and temporal domains were analysed. Statistical analyses included Wilcoxon tests, correlations, linear mixed models (LMMs), and machine learning (ML) models, adjusting for covariates.

Results: Post-intervention, the cold group showed significantly higher cortisol and state anger. Stress-related speech changes occurred across domains. Alpha ratio decreased and MFCC3 increased post-stress in the cold group, associated with cortisol and robust to sex and baseline levels. Cortisol-speech correlations were significant in the cold group, including sex-specific patterns. LMMs indicated baseline cortisol influenced feature changes, differing by sex. ML models modestly predicted SECPT group membership (AUC = 0.55) and showed moderate accuracy estimating cortisol and STAXI scores, with mean absolute errors corresponding to ∼ 24-38% and ∼16-28% of observed ranges, respectively.

Conclusion: This study demonstrates the potential of speech features as objective stress markers, revealing associations with cortisol and state anger. Speech analysis may offer a valuable, non-invasive tool for assessing stress responses, with notable sex differences in vocal biomarkers.

Background: Major depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-HT1A and 5-HT2C receptors. Its precise mechanisms remain under investigation.

Objectives: (1) To consolidate evidence on psilocybin’s efficacy and safety for depression and the role of 5HT2a, (2) to identify limitations in the literature, and (3) to highlight areas needing further research.

Methods: This systematic review follows PRISMA guidelines and analyses 22 studies, including randomised controlled trials (RCTs) and open-label studies. The studies cover various populations, including individuals with treatment-resistant depression, different dosing regimens, and adjunctive therapies.

Results: Psilocybin therapy shows substantial and rapid antidepressant effects, often after one or two sessions with psychological support. Improvements are sustained for weeks or months in many cases. Psilocybin is generally well-tolerated, with mild adverse effects such as anxiety during administration and transient headaches, which are manageable in controlled settings.

Conclusions: Psilocybin demonstrates promise as a novel treatment for depression, especially for individuals unresponsive to conventional antidepressants. Further research is needed to refine dosing, explore long-term effects, and understand its mechanisms of action.

Objectives: There are differences in IgA responses to tryptophan catabolites (TRYCATs) in major neurocognitive psychosis (MNP) versus simple neurocognitive psychosis (SNP) and normal controls. MNP and SNP are distinct schizophrenia classes which are differentiated by neurocognitive deficits, phenome features, and biomarker pathways. Nevertheless, there is no data on serum concentrations of those TRYCATs in MNP and SNP. The aim of the present study is to examine serum concentrations of tryptophan and TRYCATs in MNP versus SNP and controls.

Methods: This case-control study examines serum levels of tryptophan and TRYCATs in 52 MNP patients, 68 SNP patients and 60 controls in association with overall severity of schizophrenia (OSOS).

Results: MNP patients show lower tryptophan, kynurenic acid (KA), 3-OH-anthranilic acid (3HAA), and higher anthranilic acid (AA) and quinolinic acid (QA) than SNP patients and controls. There were no differences between SNP and controls in these TRYCATs. Kynurenine (KYN) was lower in MNP+SNP than in controls. We found that 36.5% of the variance in OSOS was explained by the combined effects of lowered tryptophan, KA, and 3-HK, and increased QA and AA. The most important biomarkers of MNP and OSOS were the QA/KA ratio followed by the QA/3HAA ratio.

Conclusions: The alterations in serum TRYCAT levels further emphasize that MNP and SNP represent two biologically distinct subtypes of schizophrenia. The reductions in TRYCATs diminish the antioxidant and immunoregulatory functions of the TRYCAT pathway. Elevated QA levels may exacerbate the disruption of the blood-brain barrier and the immune-related and oxidative neurotoxicity in MNP.

Background: Autoimmune thyroid disease (AITD) and major depressive disorder (MDD) are common genetic diseases. The comorbidity of AITD and MDD has been widely demonstrated by large amounts of epidemiological studies. However, the genetic architectures of the comorbidity remain unknown.

Methods: We use large-scale GWAS summary data and novel genetic statistical methods to assess the genetic correlation and potential causality between AITD and MDD disorders. We perform cross-trait GWAS meta-analyses to identify genetic risk variants not previously associated with the individual traits. And we use summary-data-based mendelian randomisation to identify putative functional genes shared between diseases.

Results: Both global and local genetic correlation study confirmed the genetic correlation of AITD and MDD. Through multi-trait analysis of GWAS (MTAG), we identified 112 SNPs associated with the conjoint phenotype, but not with individual traits. Mendelian randomisation confirmed the causal relationship between MDD (exposure) and AITD (outcome). The summary-based mendelian randomisation study found two plausible functional genes for AITD and MDD comorbidity.

Conclusions: AITD and MDD are genetically correlated in global and local chromosomal regions. MR analyses support a putative casual effect of MDD on AITD risk, though residual pleiotropy or confounding cannot be fully excluded. These findings highlight the need for triangulation with experimental and longitudinal studies to confirm causality.

Objective: Patient-Initiated Brief Admission (PIBA) is an intervention designed to provide constructive crisis management for patients. The purpose of this study was to evaluate outcomes in healthcare utilisation and self-inflicted injuries at one Swedish Hospital where PIBA was implemented in late 2017.

Methods: Patients who signed a PIBA-contract between 2017 and 2023 were included in the study. Data on inpatient care, contacts with the psychiatric emergency department and self-inflicted injuries that resulted in contact with medical care were collected from patients' medical records. Effects of PIBA were assessed using paired t-tests, comparing pre-post changes 0.5, 1 and 2 years, from initiation of PIBA-contract, respectively.

Results: Data from a total of 38 patients were analysed. There was a marked decrease in inpatient care from voluntary admissions in the first six months after initiation of PIBA. There was also a significant decrease in number of contacts with the psychiatric emergency department (for all patients) in the 1-year pre-post comparison, but not for the 0.5- and 2-year pre-post comparisons. There were no significant reductions in compulsory inpatient care or self-inflicted injuries in our cohort. Patients with contracts extending over several years appeared stable, on average, in their use of care and prevalence of intoxications.

Conclusion: The main effect on inpatient care after initiation of PIBA was a reduction in voluntary admissions, coinciding with a shift from voluntary admissions in favour of PIBA. The results support a more widespread utilisation of PIBA from a health-economic perspective.

Background: Metabolic syndrome (MetS) is highly prevalent among adults and is frequently accompanied by depressive symptoms. While high-sensitivity C-reactive protein (hsCRP) has been proposed as a potential indicator of depression, existing evidence remains inconclusive.

Objective: This study aimed to determine whether increased serum hsCRP or other immune-metabolic biomarkers are associated with depressive symptoms in drug-naïve individuals with obesity and MetS.

Methods: A total of 88 drug-naïve patients with obesity and MetS but without coronary-artery disease were enrolled and serum levels of neuro-immune and metabolic biomarkers were assessed.

Results: In MetS, the severity of depression, as assessed using the von Zerssen Depression Rating (VZDR) scale was significantly associated with interleukin (IL)-6, leukocyte numbers, triglyceride x glucose (Tyg) index, low-density lipoprotein cholesterol, Apolipoprotein B (all positively) and mean platelet volume (MPV), visfatin and adiponectin (all negatively). There were no significant associations between hsCRP and severity of depression. In MetS patients, hsCRP is strongly associated with increased leukocyte numbers, alkaline phosphatase, γ-glutamyl transferase, uric acid, platelet numbers and MPV, thereby shaping a distinct subtype of MetS, which is not related to depression.

Conclusions: Our findings indicate that depressive symptoms in MetS patients are associated with immune-metabolic biomarkers indicating immune activation, atherogenicity and insulin resistance, but not with hsCRP. The reason is that hsCRP in MetS is a biomarker of a specific MetS subtype that is characterized by megakaryopoiesis, hepatocyte activation, and uric acid production, which were not associated with depression.

Objective: By synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes.

Methods: A PubMed literature search covering the past 30 years was conducted using keywords such as '5-HT2A receptor', 'psychedelics', 'immune system', and 'HPA axis'. Studies were included if they addressed the effects of 5-HT2AR psychedelics on immune function, neuroimmune interactions, or HPA axis involvement. This narrative review synthesises evidence highlighting the bi-directional effects of 5-HT2AR psychedelics between the immune and nervous systems, identified through this search process.

Results: Preclinical and clinical studies report that 5-HT2AR psychedelics have some direct immunomodulatory properties with downregulation of gene regulators like NF-κB, and reduced cytokine expression such as TNF-α, IL-6, and IL-1β at a central and peripheral level, accompanied by modulation of corticotrophin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and cortisol. Direct immunomodulatory effects are mediated by pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor. Immunomodulation is further mediated indirectly via the HPA axis.

Conclusion: Further studies will determine the molecular and cellular mechanisms underlying these immunomodulatory effects. There is growing interest in the potential of 5-HT2AR psychedelics for treating a range of mental health and brain disorders. In keeping with their immunomodulatory actions, the likely modulation of brain glia and glial-neuronal interaction remains to be determined, representing a promising direction of further research on the therapeutic potential of 5-HT2AR psychedelics.

Objective: This study aimed to examine the relationship between fibroblast growth factor 19 (FGF19) and depressive symptoms, measured by Beck's Depression Inventory (BDI) scores and investigate the moderating role of smoking.

Methods: This study involved 156 Chinese adult males (78 smokers and 78 non-smokers) from September 2014 to January 2016. The severity of depressive symptoms was evaluated using the BDI scores. Spearman rank correlation analyses were used to investigate the relationship between cerebrospinal fluid (CSF) FGF19 levels and BDI scores. Additionally, moderation and simple slope analyses were applied to assess the moderating effect of smoking on the relationship between the two.

Results: FGF19 levels were significantly associated with BDI scores across all participants (r = 0.26, p < 0.001). Smokers had higher CSF FGF19 levels and BDI scores compared to non-smokers (445.9 ± 272.7 pg/ml vs 229.6 ± 162.7 pg/ml, p < 0.001; 2.7 ± 3.0 vs 1.3 ± 2.4, p < 0.001). CSF FGF19 levels were positively associated with BDI scores in non-smokers (r = 0.27, p = 0.015), but no similar association was found among smokers (r = -0.11, p = 0.32). Linear regression revealed a positive correlation between FGF19 and BDI scores (β = 0.173, t = 2.161, 95% CI: 0.015-0.331, p < 0.05), which was negatively impacted by smoking (β = -0.873, t = -4.644, 95% CI: -1.244 to -0.501, p < 0.001).

Conclusion: These results highlight the potential role of FGF19 in individuals at risk for presence of or further development of depressive symptoms and underscore the importance of considering smoking status when examining this association.