Acta Neuropsychiatrica最新文献

Objective: Accelerated ageing indexed by telomere attrition is suggested in schizophrenia spectrum- (SCZ) and bipolar disorders (BD). While inflammation may promote telomere shortening, few studies have investigated the association between telomere length (TL) and markers of immune activation and inflammation in severe mental disorders.

Methods: Leucocyte TL defined as telomere template/amount of single-copy gene template (T/S ratio), was determined in participants with SCZ (N = 301) or BD (N = 211) and a healthy control group (HC, N = 378). TL was analysed with linear regressions for associations with levels of 12 immune markers linked to SCZ or BD. Adjustments were made for a broad range of potential confounding variables. TL was measured by quantitative polymerase chain reaction (qPCR) and the immune markers were measured by enzyme immunoassays.

Results: A positive association between levels of soluble tumour necrosis factor receptor 1A (sTNF-R1) and TL in SCZ (β = 0.191, p = 0.012) was observed. Plasma levels of the other immune markers were not significantly associated with TL in the BD, SCZ or HC groups.

Conclusion: There was limited evidence of association between immune markers and TL in SCZ and BD. The results provide little support for involvement of immune dysregulation, as reflected by current systemic markers, in telomere attrition-related accelerated ageing in severe mental disorders.

Objective: Ultrasonic vocalisations (USVs) emitted by rats may reflect affective states. Specifically, 50 kHz calls emitted during juvenile playing are associated with positive affect. Given that depression is characterised by profound alterations in this domain, we proposed that USV calls may configure a suitable tool for assessing depressive-like states. Utilising the Flinders Sensitive Line (FSL), a well-established animal model of depression, we assessed USV calls emitted by rats during tickling, a procedure based on juvenile rats' rough-and-tumble play.

Methods: Juvenile FSL rats and their control counterparts, the Flinders Resistant Line (FRL) and Sprague Dawley, were submitted to tickling sessions to imitate rats playing behaviour. The rats were tickled daily for 6 weeks starting at PND21. Tickling sessions were recorded for further acoustic analysis of 50 kHz calls.

Results: Tickling increased 50 kHz calls in all the strains. FSL rats emitted more calls than control strains and exhibited a higher number of flat-trill combination calls.

Conclusion: Tickling is a robust method for inducing 50 kHz USV calls. Analysing USV calls emitted during tickling configurates a suitable method for studying affective states relevant to depression. FSL rats did not present anhedonia but rather higher reward sensitivity, which may underlie their stress vulnerability.

Objective: Folate and cobalamin deficiency or impaired function due to genetic variants in key enzymes have been associated with neuropsychiatric symptoms. The aim of this study was to compare folate and cobalamin status in patients admitted to an acute psychiatric unit to patients from primary health care in order to reveal factors which may be important in the follow-up of patients with mental disorders.

Methods: Anonymous blood samples tested for folate, cobalamin, the metabolic marker total homocysteine (tHcy), creatinine and glomerular filtration rate as well as age and gender in patients admitted to a psychiatric acute unit (n = 981) and patients from primary health care (controls) (n = 32,201) were reviewed retrospectively.

Results: Median serum folate was 18% lower and median serum cobalamin was 11% higher in patients with mental disorders compared to controls. Folate deficiency was associated with 54% higher median tHcy levels among patients with mental disorders compared to controls. The prevalence of folate deficiency was 31% and of cobalamin deficiency 6% in patients admitted to a psychiatric acute unit in a Norwegian hospital in 2024.

Conclusion: Folate, but not cobalamin deficiency, was prevalent in Norwegian patients with mental disorders. The higher tHcy levels in folate-deficient patients with mental disorders indicate an impaired folate metabolism, which might be related to genetic factors, such as polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Ensuring a serum folate concentration above 15 nmol/L and a serum cobalamin above 250 pmol/L might improve symptoms in patients with mental disorders.

Objectives: Cognitive function plays a pivotal role in assessing an individual's quality of life. This research aimed to investigate how azelaic acid (AzA), a natural dicarboxylic acid with antioxidant and anti-inflammatory properties, affects aluminium chloride (AlCl₃)-induced behavioural changes and biochemical alterations in the hippocampus of rats.

Methods: Thirty-two male Wistar rats divided into four groups received distilled water, AzA 50 mg/kg, AlCl₃ 100 mg/kg and AzA plus AlCl₃, respectively, by oral gavage for 6 weeks. Behavioural changes were evaluated using open-field maze, elevated plus maze, novel object recognition (NOR), passive avoidance task, and Morris water maze (MWM) tests. Also, malondialdehyde (MDA), carbonyl protein, tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor-kappa B (NF-κB), C/EBP homologous protein (CHOP), glycogen synthase kinase-3 beta (GSK-3β), brain-derived neurotrophic factor (BDNF) and acetylcholinesterase (AChE) activity were examined.

Results: AzA significantly affected AlCl₃-provoked anxiety-like behaviours and learning and memory impairments. It also reduced the toxic effect of AlCl₃ on MDA, carbonyl protein, TNF-α, IL-1β, NF-κB and GSK-3β status; however, its beneficial effects on AlCl₃-induced changes of CHOP, BDNF and AChE activity were not significant.

Conclusion: These findings disclosed that AzA could improve behavioural and cognitive function and almost limit the oxidative stress and neuroinflammation caused by AlCl₃.

Objective: Psychotic disorders are characterised by abnormalities in the synchronisation of neuronal responses. A 40 Hz gamma band deficit during auditory steady-state response (ASSR) measured by electroencephalogram (EEG) is a robust observation in psychosis and is associated with symptoms and functional deficits. However, the majority of ASSR studies focus on specific electrode sites, while whole scalp analysis using all channels, and the association with clinical symptoms, are rare.

Methods: In this study, we use whole-scalp 40 Hz ASSR EEG measurements – power and phase-locking factor – to establish deficits in early-stage psychosis (ESP) subjects, classify ESP status using an ensemble of machine learning techniques, identify correlates with principal components obtained from clinical/demographic/functioning variables, and correlate functional outcome after a short-term follow-up.

Results: We identified significant spatially-distributed group level differences for power and phase locking. The performance of different machine learning techniques and interpretation of the extracted feature importance indicate that phase locking has a more predictive and parsimonious pattern than power. Phase locking is also associated with principal components composed of measures of cognitive processes. Short-term functional outcome is associated with baseline 40 Hz ASSR signals from the FCz and other channels in both phase locking and power.

Conclusion: This whole-scalp EEG study provides additional evidence to link deficits in 40 Hz ASSRs with cognition and functioning in ESP, and corroborates with prior studies of phase locking from a subset of EEG channels. Confirming 40 Hz ASSR deficits serves as a candidate phenotype to identify circuit dysfunctions and a biomarker for clinical outcomes in psychosis.

Objective: Combining different pharmaceuticals may be beneficial when treating disorders with complex neurobiology, including alcohol use disorder (AUD). The gut-brain peptides amylin and GLP-1 may be of potential interest as they individually reduce alcohol intake in rodents. While the combination of amylin receptor (AMYR) and glucagon-like peptide-1 receptor (GLP-1R) agonists have been found to decrease feeding and body weight in obese male rats synergistically, their combined impact on alcohol intake is unknown.

Methods: Therefore, the effect of the combination of an AMYR (salmon calcitonin (sCT)) and a GLP-1R (dulaglutide) agonist on alcohol intake in rats of both sexes was explored in two separate alcohol-drinking experiments. The first alcohol-drinking experiment evaluated the potential of adding sCT to an ongoing dulaglutide treatment, whereas the second alcohol-drinking experiment examined the effect when adding sCT and dulaglutide simultaneously.

Results: When adding sCT to an ongoing dulaglutide treatment, a reduction in alcohol intake was observed in both male and female rats. However, when combining sCT and dulaglutide simultaneously, an initial reduction in alcohol intake was observed in rats of both sexes, whereas tolerance towards treatment was observed. In both alcohol-drinking experiments, this treatment combination consistently decreased food consumption and body weight in males and females. While the treatment combination did not affect inflammatory mediators, the gene expression of AMYR or GLP-1R, it changed fat tissue morphology.

Conclusions: Further investigation needs to be done on the combination of AMYR and GLP-1R agonists to assess their combined effects on alcohol intake.

The dorsal midbrain comprises dorsal columns of the periaqueductal grey matter and corpora quadrigemina. These structures are rich in beta-endorphinergic and leu-enkephalinergic neurons and receive GABAergic inputs from substantia nigra pars reticulata. Although the inferior colliculus (IC) is mainly involved in the acoustic pathways, the electrical and chemical stimulation of central and pericentral nuclei of the IC elicits a vigorous defensive behaviour. The defensive immobility and escape elicited by IC activation is commonly related to panic-like emotional states. To investigate the role of κ-opioid receptor of the IC in the antiaversive effects of endogenous opioid receptor blockade in a dangerous situation, male Wistar rats were pretreated in the IC with the κ-opioid receptor-selective antagonist nor-binaltorphimine at different concentrations and submitted to the non-enriched polygonal arena for a snake panic test in the presence of a rattlesnake and, after 24 h, prey were resubmitted to the experimental context. The snakes elicited in prey a set of antipredatory behaviours, such as the anxiety-like responses of defensive attention and risk assessment, and the panic-like reactions of defensive immobility and either escape or active avoidance during the elaboration of unconditioned and conditioned fear-related responses. Pretreatment of the IC with microinjections of nor-binaltorphimine at higher concentrations significantly decreased the frequency and duration of both anxiety- and panic-attack-like behaviours. These findings suggest that κ-opioid receptor blockade in the IC causes anxiolytic- and panicolytic-like responses in threatening conditions, and that kappa-opioid receptor-selective antagonists can be a putative coadjutant treatment for panic syndrome treatment.

This study aims to assess the correlation between NAA (N-acetyl-l-aspartate), CHO (choline), and CRE (creatine) levels in the hippocampus regions of individuals suffering from obsessive-compulsive disorder (OCD) and defensive styles of the ego.The study group was composed of twenty patients with OCD and twenty healthy controls. NAA, CHO, and CRE values in the hippocampal region using proton magnetic resonance spectroscopy (1H-MRS) were measured. Participants' defense styles were ascertained by administering the Defense Style Questionnaire-40.The patient group's NAA levels were considerably lower than the control group's on both sides of the hippocampus. The levels of CHO and CRE did not significantly differ between the two groups. The following statistically significant correlations were discovered: in the comparison group, there were negative correlations between the scores of mature defense styles and the right and left CHO levels, as well as between the immature defense mechanism scores and the right NAA levels in both the patient and control groups. In the patient group, there were also negative correlations between the left NAA values and the scores of mature defense styles.OCD patients have lower levels of NAA in the hippocampus. To validate and extend the current findings, more research involving a greater sample size is required.

Objective: The objective of the current research is to study the serum levels of ischemia modified albumin (IMA), a new oxidative stress indicator, and various peptides (galanin, alarin, and meteorin-like protein) that may affect the pathophysiology of schizophrenia, determine their relationship with clinical features and each other, and compare them to those in healthy controls.

Materials and methods: This is a cross-sectional study consisting of 45 individuals with schizophrenia who are in remission and 45 healthy individuals. The differences and relationships between categorical variables and serum protein levels of the patient and control groups were statistically analysed. Receiver operating characteristics analysis was used for the diagnostic decision-making properties of serum protein levels to predict the presence of the disease.

Results: In comparison with the control group, the median levels of serum proteins galanin and alarin were statistically lower in the patient group, whereas METRNL and IMA levels were higher. Considering the predictive values of serum proteins in the diagnosis of the disease, it was observed that serum galanin, alarin, and IMA levels had a sensitivity and specificity higher than 80%, followed by METRNL with 73.3% sensitivity and 66.7% specificity.

Conclusion: Our findings reveal galanin, alarin, meteorin-like protein, and IMA are important molecules with high sensitivity and specificity in diagnosing schizophrenia. Furthermore, we think that further studies are needed to use them as reliable parameters in terms of clinical course, classification, and prognosis in explaining the etiopathogenesis of the disease.