Acta Neuropsychiatrica最新文献

Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N⁶ (m⁶A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m⁶A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt's test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m⁶A methylation has potential for neuropsychiatric drug development.

There is a high prevalence of neuropsychiatric disorders in myotonic dystrophy types 1 and 2 (DM1 and DM2), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in DM1, and depression and anxiety in both DMs. The aim of this systematic review and meta-analysis was to estimate the prevalence of ASD, ADHD, depression and anxiety in the population with DM, and their association with disease onset. A systematic search of Medline, Scopus, Web of Science, and the Cochrane Library was conducted from inception to November 2023. Observational studies estimating the prevalence of these disorders in DM1 or DM2 were included. A meta-analysis of the prevalence of these disorders and an association study with disease onset by prevalence ratio meta-analysis were performed. Thirty-eight studies were included. In DM1, the prevalence of ASD was 14%, with congenital onset being 79% more common than juvenile onset, while the prevalence of ADHD was 21%, with no difference between congenital and juvenile onset, and the prevalence of depression and anxiety were 14% and 16%. Depression was more common in the adult onset. Finally, the prevalence of depression in DM2 was 16%. A higher prevalence of neuropsychiatric disorders is observed in individuals with DM1 and DM2 than in the general population. Therefore, actively screening for congenital and juvenile neurodevelopmental disorders in DM1 and emotional disorders in DM1 and DM2 may improve the quality of life of those affected.

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.

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions, either unilaterally (left or right) or bilaterally, can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention. The analysis is based on retrospective data from a clinical intervention. We administered test of variables of attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10-20 EEG convention, for 20 mins in each session. We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time (p = 0.0002), increase in d-Prime (separability of targets and non-targets; p = 0.0157), and decrease in commission error rate (p = 0.0116). The mean RT and omission error rate largely remained unchanged. Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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: To investigate the effects of cannabidiol (CBD) on emotional and cognitive symptoms in rats with intra-nigral 6-hydroxydopamine (6-OHDA) lesions.

Methods: Adult male Wistar rats received bilateral intranigral 6-OHDA infusions and were tested in a battery of behavioural paradigms to evaluate non-motor symptoms. The brains were obtained to evaluate the effects of CBD on hippocampal neurogenesis.

Results: 6-OHDA-lesioned rats exhibited memory impairments and despair-like behaviour in the novelty-suppressed feeding test and forced swim test, respectively. The animals also exhibited dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), striatum, and ventral tegmental area and a reduction of hippocampal neurogenesis. CBD decreased dopaminergic neuronal loss in the SNpc, reduced the mortality rate and decreased neuroinflammation in 6-OHDA-lesioned rats. In parallel, CBD prevented memory impairments and attenuated despair-like behaviour that were induced by bilateral intranigral 6-OHDA lesions. Repeated treatment with CBD favoured the neuronal maturation of newborn neurons in the hippocampus in Parkinsonian rats.

Conclusion: The present findings suggest a potential beneficial effect of CBD on non-motor symptoms induced by intra-nigral 6-OHDA infusion in rats.

Objective: Preclinical studies suggest that cannabidiol (CBD), a non-intoxicating phytocannabinoid, may reduce addiction-related behaviours for various drug classes in rodents, including ethanol, opiates, and psychostimulants. CBD modulates contextual memories and responses to reward stimuli. Nonetheless, research on the impact of CBD on cocaine addiction-like behaviors is limited and requires further clarification. This study tested the hypothesis that CBD administration inhibits the acquisition and retrieval of cocaine-induced conditioned place preference (CPP) in adult male and female C57BL6/J mice. We also ought to characterise a 5-day CPP protocol in these animals.

Methods: Male and female C57BL/6J mice were administered CBD (3, 10, and 30 mg/kg) 30 minutes before cocaine (15 mg/kg) acquisition of expression of CPP.

Results: Cocaine induces a CPP in both female and male mice in the 5-day CPP protocol. CBD failed to prevent the acquisition or retrieval of place preference induced by cocaine. CBD did not decrease the time spent on the side paired with cocaine at any of the doses tested in male and female mice, in either acquisition or expression of contextual memory.

Conclusion: This study found no support for the hypothesis that CBD decreases reward memory involved in the formation of cocaine addiction. Further research is necessary to investigate the involvement of CBD in other behavioural responses to cocaine and other psychostimulant drugs. This study, however, characterised a 5-day CPP protocol for both female and male C57BL/6J mice.

Objective: The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB₁), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB₁ have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB₁ receptors and TRPV1 channels in learned fear processing.

Methods: We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning.

Results: TRPV1 and CB₁ receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB₁ restrains fear responses.

Conclusion: TRPV1 and CB₁ seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning.

Background: Cannabidiol (CBD) is one of the main cannabinoids present in Cannabis sativa female flowers. Previous investigation has already provided insights into the CBD molecular mechanism; however, there is no transcriptome data for CBD effects on hippocampal subfields. Here, we investigate transcriptomic changes in dorsal and ventral CA1 of adult mice hippocampus after 100 mg/kg of CBD administration (i.p.) for one or seven consecutive days.

Methods: C57BL/6JUnib mice were treated with either vehicle or CBD for 1 or 7 days. The collected brains were sectioned, and the hippocampal sub-regions were laser microdissected for RNA-Seq analysis.

Results: The transcriptome analysis following 7 days of CBD administration indicates the differential expression of 1559 genes in dCA1 and 2924 genes in vCA1. Furthermore, GO/KEGG analysis identified 88 significantly enriched biological process and 26 significantly enriched pathways for dCBD7, whereas vCBD7 revealed 128 enriched BPs and 24 pathways.

Conclusion: This dataset indicates a widespread decrease of electron transport chain and ribosome biogenesis transcripts in CA1, while chromatin modifications and synapse organization transcripts were increased following CBD administration for 7 days.