Acta Neuropsychiatrica最新文献

Lewy body dementias (LBD) are the second most common dementia. Several genes have been associated with LBD, but little is known about their contributions to LBD pathophysiology. Each gene may transcribe multiple RNA, and LBD brains have extensive RNA splicing dysregulation. Hence, we completed the first transcriptome-wide transcript-level differential expression analysis of post-mortem LBD brains for gaining more insights into LBD molecular pathology that are essential for facilitating discovery of novel therapeutic targets and biomarkers for LBD. We completed transcript-level quantification of next-generation RNA-sequencing data from post-mortem anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC) of people with pathology-verified LBD (LBD = 14; Controls = 7) using Salmon. We identified differentially expressed transcripts (DET) using edgeR and investigated their functional implications using DAVID. We performed transcriptome-wide alternative splicing analysis using DRIMseq. We identified 74 DET in ACC and 96 DET in DLPFC after Benjamini-Hochberg false discovery rate (FDR) correction (5%). There were 135 and 98 FDR-corrected alternatively spliced genes in ACC and DLPFC of LBD brains, respectively. Identified DET may contribute to LBD pathology by altering DNA repair, apoptosis, neuroplasticity, protein phosphorylation, and regulation of RNA transcription. We confirm widespread alternative splicing and absence of chronic neuroinflammation in LBD brains. Transcript-level differential expression analysis can reveal specific DET that cannot be detected by gene-level expression analyses. Therapeutic and diagnostic biomarker potential of identified DET, especially those from TMEM18, MICB, MPO, and GABRB3, warrant further investigation. Future LBD blood-based biomarker studies should prioritise measuring the identified DET in small extracellular vesicles.

Rewards are rewarding owing to their hedonic or metabolic value. Individual differences in sensitivity to rewards are predictive of mental health problems but may reflect variation in metabolic types. We have assessed the association of two distinguishable aspects of reward sensitivity, openness to rewards (the striving towards multiple rewards) and insatiability by reward (the strong pursuit and fixation to a particular reward), with measures of metabolism and activity in a longitudinal study of representative birth cohort samples. We used data of the Estonian Children Personality Behaviour and Health Study (original n = 1238) collected at age 15, 18 and 25. Reward sensitivity and physical activity were self-reported during a laboratory visit, when also blood sampling, measurement of blood pressure, height and weight, aerobic exercise testing and the diet interview, after the participants had kept food diary, took place. In the younger cohort, physical activity was also assessed by accelerometry at age 18 and 25. Across adolescence and young adulthood, openness to rewards was positively associated with physical activity and negatively with blood pressure and serum levels of glucose, insulin and cholesterol levels. In contrast, insatiability by reward was positively associated with serum triglyceride levels and negatively with energy intake and cardiorespiratory fitness. In conclusion, the two facets of reward sensitivity have a fairly different association with a variety of metabolic and health-related measures. This may explain the variable findings in literature, and suggests that individual differences in reward sensitivity are part of a complex physiological variability, including energy expenditure profiles.

This study presents a comprehensive analysis of recent mental illness research by utilizing an advanced bibliographic method capable of analyzing up to 12,965 papers indexed in the Web of Science database, overcoming the limitations of traditional tools like VOSviewer, which typically analyze fewer than 1,000 papers. By examining a vast dataset, this study identifies key trends, significant keywords, and prominent contributors, including leading researchers, universities, and countries/regions, in the field of mental illness research. Additionally, the study highlights eight major contributors to mental health problems, offering critical insights into the field’s current state. The findings underscore the importance of advanced bibliographic methods in providing a more detailed and accurate overview of mental illness research. This analysis not only enhances the understanding of young scholars entering the field but also uncovers significant trends and identifies notable gaps in the literature. The study advocates for continued innovation and interdisciplinary collaboration to deepen understanding and address unresolved challenges in mental health research.

Objective: This study aimed to utilise graph theory to explore the functional brain networks in individuals with tic disorders and to investigate resting-state functional connectivity changes in critical brain regions associated with tic disorders.

Methods: Participants comprised individuals with tic disorders and age-matched healthy controls, ranging from 6 to 18 years old, all recruited from Korea University Guro Hospital. We ensured a medication-naïve cohort by excluding participants exposed to psychotropic medications for at least three weeks prior to the study. Data included structural and resting-state functional MRI scans, analysed with the CONN-fMRI Functional Connectivity toolbox v20b. The analysis included 22 patients (18 males, 4 females) and 26 controls (14 males, 12 females).

Results: Significantly increased global efficiency was observed in the left inferior frontal gyrus pars opercularis among tic disorder patients compared to controls. Furthermore, this region displayed enhanced resting-state functional connectivity with its right counterpart in patients versus controls.

Conclusion: The inferior frontal gyrus pars opercularis, known for its inhibitory role, may reflect adaptive functional adjustments in response to tic symptoms. Increased hubness of the inferior frontal gyrus pars opercularis possibly represents functional adjustments in response to tic symptoms. The identified brain region with increased efficiency and connectivity presents a promising avenue for further research into tic expression and control mechanisms.

Objective: Time distortions characterise severe mental disorders, exhibiting different clinical and neurobiological manifestations. This systematic review aims to explore the existing literature encompassing experimental studies on time perception in patients with bipolar disorder (BD), considering psychopathological and cognitive correlates.

Methods: Studies using an experimental paradigm to objectively measure the capacity to judge time have been searched for. Selected studies have been described based on whether i) explicit or implicit time perception was investigated, ii) the temporal intervals involved were sub-second or supra-second, and iii) a perceptual or motor timing paradigm was used.

Results: Only 11 met the criteria for inclusion in the review. The available literature shows that the performance of BD patients mostly aligns with controls within sub-second timeframes (six articles), while a different pattern emerges within supra-second intervals based on the clinical phase of the disease (seven articles). Specifically, for longer temporal spans, BD patients tend to overestimate the duration during manic states and underestimate it during depressive states. Notably, no studies have directly investigated the neurobiological mechanisms associated with time perception.

Conclusion: This review indicates that BD patients exhibit time perception similar to controls within sub-second intervals, but tend to overestimate time and underestimate it based on the clinical phase within supra-second intervals. Expanding the understanding of time perception in BD, particularly in relation to clinical phases and cognitive function, is of great importance. Such insights could deepen our understanding of the disorder, refine diagnostic processes, and guide the development of innovative therapeutic interventions.

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.