Though commonly used to model affective disorders, zebrafish display notable differences in terms of the structure and function of the brain serotonin system, including responses to pharmacological interventions, as compared to mammals. For example, elevation of brain serotonin following acute administration of serotonin reuptake inhibitors (SRIs) generally has anxiogenic effects, both in the clinical situation and in rodent models of anxiety, but previous research has indicated the opposite in zebrafish. However, several issues remain unresolved. We conducted a systematic review of SRI effects in zebrafish models of anxiety and, on the basis of these results, performed a series of experiments further investigating the influence of serotonin-releasing agents on anxiety-like behaviour in zebrafish, with sex-segregated wild-type animals being administered either escitalopram, or the serotonin releaser fenfluramine, in the light-dark test. In the systematic review, we find that the available literature indicates an anxiolytic-like effect of SRIs in the novel-tank diving test. Regarding the light-dark test, most studies reported no behavioural effects of SRIs, although the few that did generally saw anxiolytic-like responses. In the experimental studies, consistent anxiolytic-like effects were observed with neither sex nor habituation influencing treatment response. We find that the general effect of acute SRI administration in zebrafish indeed appears to be anxiolytic-like, indicating, at least partly, differences in the functioning of the serotonin system as compared to mammals and that caution is advised when using zebrafish to model affective disorders.

Childhood trauma can cause deficits in emotional regulation. However, few studies have investigated childhood trauma and emotional regulation skills in patients with mood disorders. We aimed to investigate how childhood trauma and Emotion Regulation Skills Questionnaire (ERSQ) scores are associated with mood disorders.

This study included 779 patients with mood disorders (major depressive disorder [MDD, n = 240], bipolar I disorder [BDI, n = 121], and bipolar II disorder [BDII, n = 418]). We used their Childhood Trauma Questionnaire-Short Form (CTQ) and ERSQ scores for the evaluation.

The between-group differences in CTQ and ERSQ scores were examined. The CTQ and ERSQ total scores were negatively correlated. Among the CTQ subscales, emotional neglect showed a significant correlation with the ERSQ total score, whereas acceptance and tolerance showed higher negative correlations with the CTQ than with the other ERSQ subscales. The negative relationship between emotional regulation and childhood trauma varied significantly depending on the group, with the BDI group showing a more prominent association than the other groups.

Based on various mood disorders, we observed associations between childhood trauma and emotional regulation skills. Consequently, our study offers notable insights for future research on the impact of childhood trauma on ERSQ.

From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that N-acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.

Here, we have utilised the concept of fuzzy logic and Karl Popper’s notion of verisimilitude to advocate navigating the complexity of psychiatric nosology, emphasising that psychiatric disorders defy Boolean logic. We underscore the importance of embracing imprecision and collecting extensive data for a more nuanced understanding of psychiatric disorders, asserting that falsifiability is crucial for scientific progress. We encourage the advancement of personalised psychiatric taxonomy, urging the continual accumulation of data to inform emerging advancements like artificial intelligence in reshaping current psychiatric nosology.

To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25–1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22–1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22–1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.

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.