Acta Neuropsychiatrica最新文献

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.

Objective: Previous studies on the aetiology of attention-deficit/hyperactivity disorder (ADHD) emphasise high heritability and the influence of maternal smoking during pregnancy, highlighting the role of gene–environment interactions. Additionally, low-grade peripheral inflammation is frequently observed in individuals with ADHD. However, the underlying neurobiological mechanisms remain unclear. We aimed to investigate neuroinflammatory signalling contributing to ADHD and explore behavioural and molecular changes in a mouse model.

Methods: We examined neuroinflammatory signalling using a perinatal nicotine exposure (PNE) model via immunohistochemistry combined with cortical thickness (CT) measurement in the subregions of the prefrontal cortex (PFC). Mice were exposed to nicotine via drinking water containing 300 μg/ml nicotine and 2% sucrose starting 2 weeks before mating until weaning to induce ADHD-like symptoms, as opposed to controls receiving drinking water containing 2% sucrose alone. Behavioural tests were conducted to assess ADHD-like behaviours and accompanying anxiety on postnatal week 5. Inflammatory pathways in the anterior cingulate cortex (ACC), prelimbic cortex (PL), and infralimbic cortex (IL) were examined using Iba-1 and NF-κB immunolabelling, and microglial morphology was analyzed.

Results: Findings showed increased CT, microglial cell number, activity, and NF-κB activation in the ACC, which correlated with attention-related impairment in PNE mice. Increased Iba-1 levels in the PL and IL, along with elevated NF-κB activation in the IL, were observed in PNE mice, which corresponded with a significant increase in anxiety-like behaviours compared to controls. PNE mice also morphologically exhibited microglia activation in all three subregions.

Conclusion: PNE contributes to ADHD development through neuroinflammatory signalling, a common end pathway.

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.