Acta Neuropsychiatrica最新文献

Objective: A previous study by our research group identified psychomotor and neurofunctional impairments following SARS-CoV-2 infection. This study continues that investigation, aiming to evaluate whether these impairments persisted over time, as part of the broader characterization of long COVID. Moreover, it was explored potential correlations with variables such as age, blood type, symptoms, and medical care.

Methods: From an initial pool of 214 subjects, 30 post-COVID-19 participants and 30 healthy controls were selected after strict exclusion criteria. The assessments protocol included eight psychomotor tests-Fine Motor Development (Diadochokinesia, Puppets, Fan, and Paper) and Balance (Immobility, Static Balance on One Foot, Feet in Line, and Persistence)-as well as three cognitive screening tasks from the Mini-Mental State Examination: Episodic Memory After Distracters, Verbal Fluency, and Clock tests. Evaluations were performed at three time points: baseline (post-COVID-19), 12 weeks, and 24 weeks. Participants were stratified by age (18-30, 31-45, and 46-64 years), symptoms profile, medical care, and blood type.

Results: COVID-19 induced psychomotor and neurofunctional sequelae lasting at least 24 weeks post-infection. These impairments were more pronounced and persistent in the 31-45-years age group, while memory-related impairments were more evident in the 18-30 age group. Body pain, coryza, and sore throat were key symptoms linked to long-term sequelae. Rh-negative blood type was suggested as a potential risk factor.

Conclusion: The findings support that long COVID included sustained psychomotor and neurofunctional sequelae, premature senescence, and associations with specific clinical and biological variables.

Objective: Investigating metabolic differences between pre-pubertal Flinders sensitive (FSL) and resistant (FRL) line rats and determine the impact of early-life adversity on these differences.

Methods: Untargeted metabolomic profiling of whole-brain tissue from postnatal day 25 Flinders line rats, exposed to maternal separation with early weaning (MSEW), or not, was done by using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS).

Results: Irrespective of MSEW, FSL rats had higher urea and lower glutamine, norvaline and valine concentrations than age-matched FRL controls. Across strains, MSEW reduced gamma-aminobutyric acid (GABA), glutamate, glutamine, lactate, phenylalanine, norvaline and valine concentrations, whist elevating 2-keto-3-methylbutyric acid, glycerophosphate, and urea. This effect was most pronounced in FRL rats.

Conclusion: Pre-pubertal FSL rats displayed distinct metabolic signatures associated with altered energy and amino acid metabolism. Early-life stress further disrupts these pathways, highlighting key metabolites as potential targets in the expansion of the biological contracts underlying the pre-pubertal FSL/FRL model.

Background: Major depressive disorder (MDD) is a neuro-immune, oxidative, and nitrosative stress (NIMETOX) disorder, in which peripheral immune-redox pathways intersect with metabolic networks leading to neurotoxicity within the limbic-prefrontal affective circuits. Comprehensive metabolomics analysis in well-phenotyped patients is vital to elucidate their metabolic profile.

Objectives: To identify metabolic abnormalities that differentiate inpatients with severe MDD from healthy controls through high-resolution, untargeted metabolomics.

Methods: Serum samples from 125 MDD inpatients and 40 healthy controls were analyzed utilizing liquid chromatography and mass spectrometry. A meticulously regulated multistage machine learning pipeline with leakage-prevention protocols was employed to analyze differences between MDD and controls and to predict phenome scores.

Results: Feature selection showed that 16 metabolites and 6 functional modules reliably distinguished MDD. The functional profile of the metabolites indicates a convergence of lipotoxicity, phospholipid remodeling, disruptions in fatty acid metabolism, mitochondrial redox imbalance, ether-lipid metabolism, and antioxidant depletion. This MDD metabotype was not affected by metabolic syndrome. A substantial portion of the variance in overall depression severity (72.5%), physiosomatic symptoms (55.8%) and suicidal ideation (23.6%) was accounted for by increased lipotoxicity, phospholipid remodeling, and fatty acid storage/signaling. The recurrence of illness (27.7%) was associated with a self-reinforcing lipid-redox-inflammatory module that maintains cellular stress.

Discussion: The MDD metabotype represents a cohesive metabolic network that is associated with the NIMETOX pathogenesis of MDD. Metabolomics provides a comprehensive foundation for subtyping and precision psychiatry. Lipoxygenase-15, lipotoxicity, phospholipase A₂, and lipid-redox intersections might be important drug targets to treat MDD.

Objective: Low heart rate variability (HRV) levels may be a susceptibility factor for major depressive disorder (MDD). Sleep-state HRV may be more likely to reveal the pathological features of MDD compared with resting state HRV (RS-HRV). This study aimed to elucidate HRV alterations in the sleep states of patients with MDD.

Methods: Physiological signal data from the resting state before sleep, first non-rapid eye movement (NREM) and rapid eye movement (REM) stages, and last NREM and REM stages were acquired using polysomnography.

Results: The RS-HRV indices (the standard deviation [SD] of all normal-to-normal [NN] intervals [SDNN], the square root of the mean of the sum of the squares of the differences between adjacent NN intervals [RMSSD], the percentage difference between adjacent NN intervals >50 ms [pNN50], high-frequency [HF], low-frequency [LF], very low frequency [VLF], SD1, and sample entropy [SampEn]) were lower in patients with MDD than in healthy controls (HCs). Patients with MDD had lower SDNN, RMSSD, pNN50, HF, LF, VLF, SD1, SD2, and SampEn and higher SD2/SD1, α1, and α2 than HCs in the NREM stage. They also had lower SDNN, RMSSD, pNN50, HF, LF, VLF, SD1, SD2, and SampEn and higher LF/HF than HCs in the REM stage. Fewer indices changed significantly during different sleep stages in patients with MDD than in HCs.

Conclusions: Patients with MDD had a generalized reduction in HRV in both RS and sleep state and decreased dynamic changes during sleep. Altered autonomic nervous system activity has been implicated in MDD pathology.

Objective: Impaired autophagy has been implicated in the pathophysiology of neurodegenerative disorders, such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). Consistent and replicated evidence indicate that Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) exert treatment and preventative effects across disparate neurologic and mental disorders, potentially through mechanisms involving autophagy. This systematic review examined the effects of GLP-1RAs on autophagy in cell and animal models of AD and PD, as a proof of concept, to determine if these agents can be repurposed for the prevention and treatment of neurodegenerative and other mental disorders.

Methods: A systematic search on PubMed, Web of Science, and OVID (Medline, Embase, and APA PsycInfo databases) was conducted from inception to June 17, 2025. Screening was performed independently by two reviewers (MCS and IH) using predefined inclusion and exclusion criteria. Subsequently, a quality assessment was conducted.

Results: The search yielded 142 studies, of which 14 were included. Across studies, GLP-1RAs (e.g., liraglutide, semaglutide, and exendin-4) autophagy-specific markers, including beclin-1, LC3-II/LC3-I, ATG7, ATG3, and LAMP1, while normalizing p62 levels.

Discussion: In addition to promoting neurogenesis, neuroplasticity, and reducing inflammation, GLP-1RAs appear to modulate molecular and cellular systems contributing to autophagy, potentially mediating their broad therapeutic effects. Collectively, these studies present promising findings of GLP-1RAs for neurodegenerative and mental disorders; however, further studies are required to establish their translatability to human populations.

Ibogaine is a psychedelic alkaloid without an approved indication. Observational clinical research shows linkages between single administration of ibogaine and relief of symptoms of neuropsychiatric conditions including substance use disorder, multiple sclerosis, and traumatic brain injury. Ibogaine has multi-receptor actions, but the neurobiological mechanisms underlying such putative effects is unknown. Here we review and discuss the relevant literature, focusing on remyelination and metabolic restoration. We provide evidence that ibogaine upregulates markers of myelination following opioid administration; that conditions such as opioid use disorder, multiple sclerosis and traumatic brain injury are characterized by white matter pathology; that decreased myelination is related to dysregulated metabolic homeostasis, ischemia and hypoxia which may also play a role in these disorders. We conclude that multi-receptor actions of ibogaine, especially its affinities for the NMDA, kappa opioid and sigma receptors, in turn account for reduction in excitotoxicity, metabolic regulation, lasting neuroplasticity and immunomodulation that facilitates neuronal repair and remyelination providing a rationale for future investigation of its use as a therapeutic agent for these common central nervous system disorders.

Objectives: Electroconvulsive therapy (ECT) is an effective treatment of severe manifestations of mental illness. Since delay in initiation of ECT can have detrimental effects, prediction of the need for ECT could improve outcomes via more timely treatment initiation. Therefore, this study aimed to predict the need for ECT following admission to a psychiatric hospital.

Methods: This study was based on electronic health record (EHR) data from routine clinical practice. Adult patients admitted to a hospital within the Psychiatric Services of the Central Denmark Region between January 2013 and November 2021 were included in the study. The outcome was initiation of ECT >7 days (to not include patients admitted for planned ECT) and ≤67 days after admission. The data was randomly split into an 85% training set and a 15% test set. On the 7^th day of the inpatient stay, machine learning models (extreme gradient boosting) were trained to predict initiation of ECT and subsequently tested on the test set.

Results: The cohort consisted of 41,610 patients with 164,961 admissions. In the held out test set, the trained model predicted ECT initiation with an area under the receiver operating characteristic curve of 0.94, 47% sensitivity, 98% specificity, positive predictive value of 24% and negative predictive value of 99%. The top predictors were the highest suicide assessment score and mean Brøset violence checklist score in the preceding three months.

Conclusions: EHR data from routine clinical practice may be used to predict need for ECT. This may lead to more timely treatment initiation.

Background: Self-regulation is central to adolescent emotional and cognitive development and deficits in self-regulation may associate with depression and anxiety. This scoping review maps the use of the Emotional Go/No-Go (EGNG), Delay Discounting Task (DDT), and Balloon Analogue Risk Task and Youth version (BART) in studies of adolescent depression and anxiety, examines consistency of task implementation, and identifies methodological and geographic gaps.

Methods: A PRISMA-ScR-compliant search was conducted in MEDLINE (PubMed), Scopus, and PsycINFO from database inception to 15 December 2025 (initial search: 1 December 2023; updated: 15 December 2025). Data were charted using a standardized form. Eligible studies included adolescents, employed EGNG, DDT, or BART, and assessed depressive or anxiety symptoms.

Results: Thirty reports were included (EGNG n = 21; DDT n = 3; BART n = 6). Twenty-six studies (87%) were conducted in high-income countries and 24 (80%) were English language. Twenty-two studies were cross-sectional (EGNG n = 18/21; DDT n = 2/3; BART n = 2/6); five employed longitudinal designs, and two employed experimental manipulations. Fourteen studies (47%) reported significant task performance associations with depression or anxiety (EGNG n = 8/21; DDT n = 2/3; BART n = 4/6); remaining studies reported no significant associations. The directionality of associations differed across study populations and methodologies.

Conclusion: The current literature is concentrated in English-speaking higher-income contexts and has yielded few and inconsistent associations with adolescent depression and anxiety. Future research should harmonize protocols, expand evidence from low- and middle-income settings, and increase longitudinal and intervention-based studies to assess sensitivity to change and clinical utility.

Objective: This study aimed to investigate leptin (LEP) (G-2548A) and leptin receptor (LEPR) (668A>G) gene polymorphisms in SCZ patients with and without suicide attempts, compared to controls.

Methods: The study included 120 patients with SCZ and 130 healthy volunteers. Sociodemographic characteristics, suicidal behavior, and symptom severity were assessed using data collection forms. Gene polymorphisms were analyzed from DNA samples using the polymerase chain reaction-restriction fragment length polymorphism.

Results: The LEP genotype distribution in SCZ patients differed significantly from controls, with the heterozygous GA genotype more frequent in controls (p = .026). Within SCZ, LEPR genotype distribution differed by suicide attempt history; the heterozygous AG genotype was more frequent in non-attempters (p = .048). Logistic regression showed that the LEPR polymorphism (p = .023), number of hospitalizations (p = .036), and PANSS-psychopathology score (p = .023) predict suicide attempt history in SCZ.

Conclusion: Our findings suggest that LEP polymorphism may contribute to SCZ susceptibility, while LEPR polymorphism may be linked to suicide attempts in SCZ.