OBJECTIVE:Cognitive dysfunction is a core feature of major depressive disorder (MDD). Although both repetitive transcranial magnetic stimulation (rTMS) and vortioxetine have demonstrated procognitive effects, direct comparative evidence remains limited. This study compared the clinical and cognitive outcomes of rTMS and vortioxetine in patients with MDD. METHODS:In this 8-week naturalistic study, 40 patients with MDD received either rTMS (n = 25) or vortioxetine (n = 15). Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Cognitive performance was evaluated with the Perceived Deficits Questionnaire-Depression (PDQ-D), Trail Making Test Part B (TMT-B), Stroop Test, and Wisconsin Card Sorting Test (WCST). Longitudinal changes were analyzed using linear mixed-effects models. Week-8 outcomes were examined using ANCOVA adjusted for baseline cognitive performance and relevant clinical covariates. RESULTS:Both groups showed significant improvements in depressive symptoms and cognitive performance over time, with no significant treatment × time interactions. Baseline cognitive performance strongly predicted week-8 outcomes. Domain-specific differences were observed in executive functioning: vortioxetine showed a modest advantage in WCST performance, whereas rTMS showed a non-significant trend toward better Stroop interference performance. No significant differences were detected in processing speed. CONCLUSION:rTMS and vortioxetine were associated with comparable improvements in depressive symptoms and cognitive functioning in patients with MDD. Baseline cognitive status appeared to be a stronger predictor of outcome than treatment modality.
OBJECTIVE:To investigate whether transcutaneous auricular vagus nerve stimulation (taVNS) modulates empathic choice, and whether any such effect differs for ingroup versus outgroup targets, in a single-session behavioural experiment. METHODS:Twenty-eight healthy East Asian participants were randomly assigned to active taVNS or sham stimulation groups. After 15 minutes of stimulation, participants completed an adapted Empathy Selection Task (EST), choosing to empathize with or describe facial expressions of ingroup (Asian) and outgroup (African) targets displaying negative emotions. Because the design was exploratory and the sample small, a generalized linear mixed model (GLMM) with a binomial distribution and logit link, modeling subject-level random intercepts, was used and effects are reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS:The sham group showed significantly lower empathic choice than the active group (β = -0.82; OR = 0.44, 95% CI [0.22, 0.90], p = 0.024). The main effect of target ethnicity was non-significant (OR = 0.88, 95% CI [0.60, 1.28], p = 0.494), indicating no detectable baseline ingroup bias. A group × ethnicity interaction (OR = 1.74, 95% CI [1.01, 3.00], p = 0.048) indicated that the taVNS effect was selectively larger for outgroup targets; this pattern survived parametric bootstrap (bootstrap p = 0.022) and Bayesian reanalysis (96.7% of the posterior above zero), though its credible interval narrowly included no effect, marking it as supported but not decisive. CONCLUSION:taVNS may increase motivational empathy and selectively enhance empathic choice toward outgroup negative emotions. These exploratory findings are consistent with, but do not directly test, the aversiveness reduction hypothesis, and require replication with autonomic measures and larger samples.
Abstract Defined by DSM-5-TR as a neurodevelopmental disorder, attention-deficit/hyperactivity disorder (ADHD) has attracted ever-mounting attention from the public, coupled with a growing interest from clinicians, researchers, and patients. This is reflected in significantly higher demand for clinical assessments and frequent media reports of a surge in ADHD cases across the lifespan. These trends are puzzling as it is unknown what they truly reflect: an improvement in clinical detection or a concerning degree of overdiagnosis? A key reason for this uncertainty is our limited understanding of the disorder and imprecision of the diagnosis – a long-running subject of criticism. To better understand these issues, in this article, we deconstruct ADHD through the lens of its DSM-5-TR diagnostic criteria – the basis upon which the diagnosis is routinely made. Our in-depth analysis reveals major problems associated with the diagnostic criteria with respect to their arbitrariness , vagueness , redundancy , and context-dependent normality , which together substantially undermine the validity and reliability of the diagnosis, and the ADHD construct itself, blunting the precision of ADHD research, clinical decisions, and the effectiveness of treatment – all of which are contingent on having a robust diagnosis in the first place. Hence, our detailed deconstruction of the diagnosis of ADHD is critical as it provides the necessary groundwork for its accurate reconstruction – an essential step towards developing a valid, reliable, and clinically meaningful diagnostic foundation that will inform research and improve clinical care for patients with attentional and hyperactivity–impulsivity problems.
BACKGROUND:Depressive disorder (DD) is a widespread mental illness that lacks objective diagnostic biomarkers, complicating early detection and personalized treatment. This study investigated the diagnostic value of serum interferon-gamma (IFN-γ), nerve growth factor (NGF), and their ratio, alongside thyroid peroxidase antibody (TPOAb) and glial fibrillary acidic protein (GFAP), in patients with DD compared to healthy controls. METHODS:A total of 238 participants (118 with DD and 120 controls) were enrolled. Depression severity was assessed using DSM-5 and HAM-D criteria. Serum biomarkers were measured using enzyme-linked immunosorbent assays (ELISA), and receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance. RESULTS:DD patients exhibited significantly lower IFN-γ and higher NGF levels than controls (both p < 0.001), resulting in a markedly reduced IFN-γ/NGF ratio. The IFN-γ/NGF ratio achieved the highest diagnostic accuracy (AUC = 0.858, sensitivity = 82.20%, specificity = 77.50%), outperforming IFN-γ (AUC = 0.766) and NGF (AUC = 0.848) alone. TPOAb and GFAP levels did not differ significantly between groups. CONCLUSION:The IFN-γ/NGF ratio is a promising biomarker for depressive disorder, offering superior diagnostic accuracy over individual immune or neurotrophic markers. This composite index may support more objective and biologically informed diagnosis in clinical psychiatry.
INTRODUCTION:Schizophrenia spectrum disorders (SSD) are complex illnesses influenced by genetic, biological and psycho-social factors, necessitating large clinical deep-phenotyped cohorts. Here, we describe the Region Midt Schizophrenia (RMS) Cohort, which aims to establish such a large, representative cohort with long-term follow-up, enabling large-scale studies on SSD etiology and prognosis. METHODS:The RMS cohort includes patients aged ≥15 years diagnosed with a first-episode SSD recruiting at 6 Danish psychiatric hospitals. Baseline and follow-up assessments at 1, 2, 3, and 12 months and 2, 3, 5, and 10 years cover sociodemographic measures, psychotic and negative symptoms, adverse childhood experiences (ACEs), level of functioning, sleep, actigraphy, cognition, side effects, and medication adherence. Blood is collected at baseline and months 3 and 12 and at years 2, 3, 5 and 10 enabling comprehensive molecular analyses, e.g. genetics and omics. Age- and sex-matched healthy controls will complete a baseline assessment including blood draw. Participants give informed consent for linkage with Danish nationwide register-based data. STATUS AND PERSPECTIVES:By February 23rd, 2026, a total of 131 participants with SSD have been recruited (109 with schizophrenia, median age 25 years (IQR 8), 54% females). Retention rates at 1, 2, 3 and 12 months are 86%, 80%, 78%, and 75%, respectively. Our vision is continuous recruitment of 100 participants/year, establishing a large, deep-phenotyped, and representative clinical cohort with long-term follow-up. The RMS cohort will serve as the basis for several studies on etiological and prognostic factors and is designed to match with similar international cohorts enabling further collaborations. ETHICS AND DISSEMINATION:The protocol has been approved by the ethics committee of the Central Denmark Region (reference: 1-10-72-147-23). Study findings will be published in peer-reviewed journals independent of whether they are positive, negative, or inconclusive, and will be presented at national and international conferences.
OBJECTIVES:Attention deficit and hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder (Drechsler et al., 2020). Recently, psychedelics have become of interest regarding developing treatment options for ADHD. The aim of this systematic review is to find all studies from the APA PsychInfo and MEDLINE databases, where psychedelics have been used for ADHD and assess whether further clinical studies are warranted. METHODS:APA PsychInfo and MEDLINE were searched on the 20th of August 2025 for studies discussing ADHD and lysergic acid diethylamide (LSD) or psilocybin or dimethyltryptamine (DMT) or mescaline or phencyclidine or 3,4-methylenedioxymethamphetamine (MDMA) or ketamine. Primary research articles in English where the effects of the psychedelics mentioned on ADHD in humans were included. RESULTS:N = 1023 results were identified. Six studies were included - one randomised controlled trial (RCT) finding no statistically important difference compared to placebo, 3 cross sectional studies where respondents reported positive effect of psychedelics and one where the statistically important improvement was measured by the Child Bipolar Questionnaire. In addition, one case study, where both, depressive symptoms and functioning improved with ketamine. CONCLUSIONS:There is not sufficient evidence to give recommendations on psychedelic use for ADHD. In addition, it is not known whether patients, whose depressive symptoms have responded positively to ketamine, have also had ADHD. Also, no research was found on how psychedelics affect patient subgroups with different etiopathology causing their symptoms. Although only six studies filled the inclusion criteria, they bring out valuable implications for further research.
Defined by DSM-5-TR as a neurodevelopmental disorder Attention-Deficit/Hyperactivity Disorder (ADHD) has attracted ever-mounting attention from the public, coupled with a growing interest from clinicians, researchers, and patients. This is reflected in significantly higher demand for clinical assessments and frequent media reports of a surge in ADHD cases across the lifespan. These trends are puzzling as it is unknown what they truly reflect: an improvement in clinical detection or a concerning degree of overdiagnosis? A key reason for this uncertainty is our limited understanding of the disorder and imprecision of the diagnosis - a long-running subject of criticism. To better understand these issues, in this article we deconstruct ADHD through the lens of its DSM-5-TR diagnostic criteria - the basis upon which the diagnosis is routinely made. Our in-depth analysis reveals major problems associated with the diagnostic criteria with respect to their arbitrariness, vagueness, redundancy, and context-dependent normality, which together substantially undermine the validity and reliability of the diagnosis, and the ADHD construct itself, blunting the precision of ADHD research, clinical decisions and the effectiveness of treatment - all of which are contingent on having a robust diagnosis in the first place. Hence, our detailed deconstruction of the diagnosis of ADHD is critical as it provides the necessary groundwork for its accurate reconstruction - an essential step towards developing a valid, reliable, and clinically meaningful diagnostic foundation that will inform research and improve clinical care for patients with attentional and hyperactivity-impulsivity problems.
BACKGROUND:Neuropeptide Y (NPY) has been implicated in stress resilience and depression, yet findings on circulating levels in major depressive disorder (MDD) remain inconsistent, possibly due to confounders such as age, sex, and body mass index (BMI). This study assessed NPY concentrations in individuals with MDD and in matched controls from the Danish PRISME cohort of public-sector employees. METHODS:We investigated plasma NPY (p-NPY) concentrations in 77 adults with a current ICD-10 diagnosis of MDD and 77 age- and sex-matched controls. Plasma samples were analysed using a commercial ELISA kit. A general linear model examined the effects of group, age, sex, and BMI, including a sex-by-group interaction. Plasma NPY values were log10-transformed prior to analysis. RESULTS:p-NPY concentrations did not differ significantly between MDD and controls (p = 0.785). No main effect of sex or sex-by-group interaction was observed (all p > 0.17), and BMI was unrelated to p-NPY (p = 0.917). By contrast, age was a strong predictor (β = 0.38, p < 0.001), explaining 13% of the variance. CONCLUSIONS:In this community-based sample of high-functioning individuals with MDD, we found no evidence of altered p-NPY concentrations compared with matched controls. Instead, age emerged as a robust determinant of circulating NPY levels, independent of depression status and BMI, after adjustment for sex. These findings suggest that peripheral NPY variation may be more strongly related to demographic factors than to depression per se in this type of cohort.
BACKGROUND:In Africa, bewitchment is described as a moral framework that helps individuals and societies make sense out of disease and misfortune. Numerous African belief systems attribute difficult-to-treat health problems to bewitchment, rather than a conventional medical diagnosis, especially if biomedical doctors are unable to resolve the condition. This study examines one such illness, known as xifula, in rural Limpopo Province, South Africa. METHODS:Using convenience sampling, 95 participants (≥18 years old) were interviewed to gauge their knowledge of the condition known as xifula. Data was analysed using NVivo software. FINDINGS:Xifula is a cultural concept of distress related to bewitchment. The most common symptom of xifula is swelling of the legs or hands, followed by chronic headaches. Participants noted that xifula can start as a minor ailment, but then grows into a larger problem. After a long period without healing, however, xifula can begin to represent a significant threat to the individual's health. Nearly all participants noted that xifula cannot be treated by Western biomedical professionals and instead requires a traditional healer to treat the condition. INTERPRETATION:This research highlights the importance of context-specific education about the diagnosis and treatment of common ailments, as beliefs about afflictions, their causes, and appropriate treatments suggest a need for tailored information. As biomedical and traditional healthcare currently exist as parallel, siloed structures of diagnosis and treatment in Africa, there should also be efforts to bridge the divide between the two.
Objectives: This study investigated whether targeting mood via sequential bilateral dorsolateral prefrontal cortex (DLPFC) tDCS could favorably affect motor function in patients maintaining a stable medication 'ON' state. Additionally, we employed wearable smart devices to objectively evaluate real-world changes in daily activity and sleep patterns, complementing traditional clinician-rated scales.Methods: PD patients with mild-to-moderate depressive symptoms were enrolled. All participants completed a 7-day baseline monitoring period using a smart band. Participants received ten sessions of bilateral tDCS targeting the DLPFC (anode F3, cathode F4) at 2 mA for 30 min, three times a week. Clinical assessments and smart band monitoring were repeated during the final week of treatment. Pre-post changes and correlations were analyzed while controlling for potential confounders.Results: Following tDCS, it was significant improvements in K-MADRS, STAI, AS, UPDRS part III, and PDQ-39. Smart device data showed a significant increase in daily step counts after treatment, while changes in physical activity time and sleep duration were not significant. Changes in step count were strongly correlated with improvements in apathy, and this relationship remained significant after confounding variables (rho = -0.76, p < 0.001).Conclusions: Bilateral DLPFC tDCS significantly improved mood and motor function in patients with PD. Smart band data further showed an increase in daily step counts after the intervention, with reductions in apathy. These findings suggest that tDCS may enhance goal-directed behavior by modulating mood-related pathways, highlighting apathy as an important therapeutic target in PD.
INTRODUCTION:Estimating the prevalence of use of substances such as heroin remains a challenge. The aim of this study is to identify the scientific publications in Spain that have used surveys to investigate heroin use, to describe their methodology and to contrast the formulation of the questions with users' input on key aspects associated with use. METHODS:A scoping review was conducted until November 2024 in MEDLINE (Ovid), EMBASE and Web of Science. The review included questionnaire-based research studies assessing heroin use in Spain. Information on study, population, data collection and consumption characteristics was compiled from each included study. In addition, in-depth interviews were conducted with Spanish heroin current users and ex-users. RESULTS:Twenty-nine questionnaire-based research studies assessing heroin use in Spain were identified; none of them were specifically oriented to estimate and characterise heroin use at the population level. Most of the studies focused on specific population groups, mainly drug users, students, or inmates. The majority addressed lifetime, past-year, and past-month use, although users found the past 3 or 6 months more relevant. Few studies explored other use characteristics; however, interviews with heroin ex-users highlighted the importance of factors like route of administration and age of first use. CONCLUSIONS:The studies identified in this review vary in terms of target population, geographic scope, reference time frame, and data collection methods. Moreover, questionnaires rarely address additional characteristics of use that are considered relevant by former users. This review identifies areas for improvement to guide future studies and refine methodological approaches.
OBJECTIVE:Anxiety disorders are prevalent neuropsychiatric conditions associated with neuroinflammation and altered cytokine signalling in the hippocampus. This study aimed to evaluate the anxiolytic-like effects of alpha-pinene and its potential modulation of hippocampal neuroinflammatory pathways in a reserpine-induced anxiety model. METHODS:Adult male Wistar rats were randomly assigned to four groups: control (vehicle), reserpine (0.5 mg/kg, i.p.), and reserpine co-treated with alpha-pinene at 50 or 100 mg/kg. Treatments were administered intraperitoneally for 10 consecutive days. Behavioural assays – including the Open Field Test, Elevated Plus Maze, and Light/Dark Box Test – assessed locomotor activity and anxiety-like behaviours. Following testing, hippocampal tissues were collected for molecular analyses, including real-time PCR for TLR4, MyD88, and NF-κB expression, and ELISA quantification of IL-1β and IL-6 levels. RESULTS:Reserpine induced robust anxiety-like behaviours, accompanied by significant upregulation of TLR4, MyD88, and NF-κB expression and increased hippocampal IL-1β and IL-6. Alpha-pinene treatment at both doses significantly attenuated anxiety-like behaviours and reduced neuroinflammatory markers, suggesting involvement of the TLR4/MyD88/NF-κB pathway. CONCLUSION:Alpha-pinene exhibits anxiolytic-like effects in reserpine-treated rats, potentially via suppression of hippocampal neuroinflammation, supporting further investigation into its therapeutic potential for anxiety disorders.
OBJECTIVE:We tested the hypothesis that resuming dietary control in early-treated phenylketonuria (PKU) is associated with improvements in white matter integrity, using data from the ReDAPT study, which previously demonstrated cognitive and psychiatric improvements with reduced phenylalanine (Phe) levels. METHODS:We re-initiated dietary control for early-treated patients with PKU and assessed the T1w/T2w ratio from standard T1-and T2-weighted magnetic resonance images, a marker of myelination and microstructural integrity. General linear mixed-effects model (GLMM) analyses were performed to assess change in the T1w/T2w ratio from baseline over twelve months after resumption of dietary control. RESULTS:Seven participants (mean age 31 years; five female) with neuroimaging were included, with a mean of 16 years off diet and baseline Phe levels of 1157 µmol/L. GLMM analyses showed significant increases in T1w/T2w ratio over time for the whole brain (β = 0.47 [95%CI = 0.28, 0.66]), left hemisphere (β = 0.36 [95%CI = 0.19, 0.54]) and right hemisphere regions of interest (β = 0.52 [95%CI = 0.30, 0.72]). Longer time off diet was also positively associated with greater T1w/T2w changes. There was no evidence for the effects of gender or age at baseline. CONCLUSIONS:This study demonstrated significant increases in the T1w/T2w ratio in PKU patients as they resumed dietary control over a 12-month period. Raw Phe levels were not strongly associated with neuroimaging measures. These findings support the importance of lifelong treatment for PKU and also demonstrate the potential reversibility of white matter changes in the disease.
OBJECTIVE:Emerging evidence suggests that immune dysregulation may play a key role in the pathophysiology of psychosis. However, longitudinal studies integrating both innate and adaptive immune components in the same sample remain scarce. This study aimed to examine a broad spectrum of immunological parameters in first-episode psychosis (FEP) patients, both at onset and after treatment, in comparison to healthy controls. METHODS:Thirty-two minimally treated FEP patients (no lifetime psychotropic exposure >1 month) and 26 healthy controls were assessed at baseline. 20 patients completed a follow-up approximately one year later. Immunological markers – including complete blood count (leukocyte, neutrophil, lymphocyte, monocyte), C-reactive protein (CRP), SAA, complement components (C3, C4), and immunoglobulins (IgG, IgA, IgM, IgE) – were measured at both time points. First-episode psychosis was confirmed using SCID (DSM-IV). Symptom severity was evaluated using PANSS and BPRS. ROC and logistic regression analyses were performed to assess predictive value. RESULTS:Neutrophil, monocyte, C3, C4 levels and neutrophil-to-lymphocyte ratio (NLR) were significantly elevated in patients at both time points, with no change over time. CRP was elevated at T1 but normalised at follow-up. In contrast, immunoglobulin levels showed temporal and dimensional associations with symptom severity. NLR was correlated with negative symptoms during the acute phase, while IgG was associated with positive symptoms during remission. Elevated NLR and C4 predicted patient status in logistic regression analysis. CONCLUSION:This longitudinal study provides a system-level immunological profile across illness phases in FEP. The findings underscore distinct and dynamic contributions of innate and adaptive immunity to the onset and progression of psychosis.
In severe cases of depression and obsessive-compulsive disorder (OCD), clomipramine is sometimes administered parenterally. This systematic review aimed to investigate whether parenteral clomipramine is superior to oral clomipramine or other treatments, primarily in terms of reducing depressive/OCD symptoms within two weeks (CRD420250654029). Medline, Embase, the Cochrane Library, and PsycInfo were searched for relevant publications. Randomized controlled trials (RCTs) without a high risk of bias formed the primary basis for the conclusions. Meta-analyses were performed when applicable. Certainty of evidence was assessed according to GRADE. The literature search identified 4973 unique publications, whereof 14 RCTs contributed data regarding the question at issue in this systematic review. The evidence synthesis revealed that parenteral clomipramine may not be superior to oral administration in terms of reducing depressive symptoms within two weeks, but a clinically relevant effect cannot be excluded (low certainty of evidence; five RCTs including 70 patients; mean difference of change in Hamilton depression rating scale scores (meta-analysis based on three RCTs): -1.27 (95% confidence interval: -3.09 to 0.54; 2, I2 = 22%). Regarding patients with OCD, no conclusion could be drawn (very low certainty of evidence; two RCTs including 47 patients; meta-analysis not conducted due to heterogeneity). Regarding comparisons with other treatments, the available RCT (depression) did not allow for conclusions, or no RCTs (OCD) were available. Current evidence indicates that parenteral administration of clomipramine may not be favourable compared to oral administration, and RCTs with relevant comparisons such as electroconvulsive therapy and ketamine are lacking.
The COVID-19 pandemic had substantial impact on healthcare systems across the globe, including psychiatric services. Use of electroconvulsive therapy (ECT), a lifesaving intervention for severe mental illness, was reported to have declined during the pandemic in several countries, but nationwide data remain scarce. Using nationwide data from the Danish National Patient Register, we examined all ECT treatments administered in Denmark from September 2019 to May 2025. Weekly treatment numbers were visualized across the three national COVID-19 lockdowns to descriptively assess changes in ECT use. A notable reduction in ECT treatments was observed in the weeks preceding and during the first lockdown (March 11 to May 18, 2020). A post-hoc estimation indicated approximately 1,366 “missed” treatments during the initial pandemic phase in 2020. When these were added to the 27,033 treatments delivered in 2020, the adjusted total approximated annual treatment volumes in 2019 and 2022, suggesting a temporary disruption rather than sustained decline. In contrast, ECT activity during the second and third lockdowns appeared largely unaffected. These findings suggest that ECT provision in Denmark was temporarily reduced during the initial phase of the pandemic but remained resilient thereafter. In the case of a future pandemic, safeguarding timely access to ECT—particularly in early phases— should be prioritized given its critical role in the treatment of severe mental illness.
Objective: The comorbidity of psychiatric and metabolic conditions is prevalent and poses a heavy burden on public health. Several biopsychosocial factors are known to influence both metabolic and psychiatric health, including inflammation, eating behavior, physical activity, and early life stress. Few studies, however, have examined the constellation of interrelationships among multiple risk domains simultaneously.Methods: Using a sample of 200 medically healthy adults enrolled in a parent study, we used Gaussian Graphical Modeling, a type of network analysis, to characterize interdependent cross-sectional associations between early life stress (childhood trauma), health behaviors (diet quality and physical activity), blood-based biomarkers of metabolic functioning (insulin resistance, HDL cholesterol, triglycerides) and inflammation (C-reactive protein [CRP]), and three domains of mental health symptoms (depressive, anxious, and post-traumatic stress symptoms). We hypothesized that the network structure would highlight a pattern whereby higher CRP, poorer diet quality, lower physical activity, and higher childhood trauma would associate with increased risk for both metabolic and psychiatric impairments.Results: Findings revealed a positive conditional association between CRP and childhood trauma, which may function as an intermediary process to increase risk for both metabolic impairments and psychiatric symptoms in adulthood. Further, higher physical activity was associated with lower insulin resistance and fewer depressive symptoms, and better diet quality was associated with lower CRP levels.Conclusion: Results highlight potential avenues for interventions aimed at reducing inflammation, improving health behavior, and addressing the effects of childhood trauma to improve physical and mental health comorbidities.
Objective: Psychedelics such as psilocybin are known for their hallucinogenic properties and have also been reported to produce long-lasting therapeutic effects in depression and possibly also other psychiatric disorders. Several lines of evidence suggest that psilocybin exerts its effects through activation of 5-HT2A receptors located postsynaptically to serotonergic neurons, for example, in the frontal cortex, parts of the limbic system, including the amygdala and hippocampus, and striatum. The present study was conducted to shed further light on psilocybin-induced changes in gene expression.Method: Samples from the medial prefrontal cortex, cingulate cortex, hippocampus, amygdala, and striatum were collected from 24 male Wistar rats 90 min after they had been injected with either saline or psilocybin (2 mg/kg) and subjected to multi-region transcriptional profiling using 3prime-RNASeq technology.Results: Nfkbia and Sgk1 were upregulated in all the studied regions, Ddit4 was upregulated in four regions, and Gpd1, Apold1, Sox9, Tsc22d3, and Slc2a1 were differentially expressed in two regions. Other cases of differentially expressed genes were region-specific.Conclusion: Whereas psilocybin was not found to alter the expression of genes encoding enzymes, transporters, or receptors implicated in the serotonergic signalling, or those specifically involved in the regulation of the synaptic activity of other neurotransmitters, a common denominator for many of the genes impacted by psilocybin is that they have previously been found to be activated by glucocorticoids.
Objective: Emotion regulation, while closely linked to depressive symptoms, has seldom been examined together with them in studies of the relationship between chronotype and suicidality. We therefore examined whether chronotype predicts suicidality through the sequential mediation of poor emotion regulation and depressive symptoms. In addition, we examined whether these mediation pathways differ between morning-type and evening-type groups.Methods: This study included 3109 Korean adults from the general population. Chronotype, depressive symptoms, emotion regulation, and suicidality were assessed using the Composite Scale of Morningness, Self-Rating Depression Scale, Emotion Regulation Skills Questionnaire, and the Suicidality module of the Mini International Neuropsychiatric Interview, respectively.Results: Chronotype did not have a direct effect on suicidality. Instead, eveningness was indirectly linked to higher suicidality. Specifically, individuals with stronger eveningness tendencies reported poorer emotion regulation, which increased depressive symptoms; depressive symptoms, in turn, predicted suicidal ideation, which emerged as a significant predictor of suicide attempts. Subgroup analyses revealed that the same sequential pathway was significant only among evening-types, but not among morning-types.Conclusions: Chronotype appears to play a role in suicide risk in the general population. Screening for chronotype and focusing on emotion regulation and depressive symptoms may enhance prevention efforts tailored to chronotype, especially for evening-type individuals.
Longitudinal studies on population representative samples offer unique insights. The Estonian Children Personality Behaviour and Health Study (ECPBHS; EstChild) was launched in 1998 on two birth cohort samples at age 9 or 15 with an exceptional participation rate, has been monitored at ages 15, 18, 25 and 33, and also recruited parents of the target subjects. This multidisciplinary investigation has been focused on behavioural neuroscience, illuminating findings on what could be discerned from biomarkers, candidate genes, gene × environment interactions, and epigenetic markers in representative samples, and in birth cohorts living through societal transformation. ECPBHS analysed how biomarkers and lifestyle are associated with real-life behaviours and developmental trajectories, phenotypes such as neuroticism, bulimia, aggressiveness or attention deficit, and outcomes from incidence of psychiatric disorders to the obtaining of university education. Novel evidence has been observed on clustering of fears and the inner structure of impulsivity and reward sensitivity, together with clues how these may have co-emerged with metabolic types. New insights have been provided to understand the classic biomarkers, cholesterol and platelet monoamine oxidase activity, as well as several functional gene variants. Hypotheses how to synthetise molecular genetics and sociology, how sex or gender matters in the light of gene × environment interactions and how family and parental roles shape the behaviour of offspring have been put forward. The ECPBHS has offered clues on why in biological psychiatry many replication attempts are predestined to fail, and how to learn from such failures.
