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The oxytocin system has been thought to contribute to obsessive-compulsive disorder (OCD). Few studies, only involving adults, have investigated this hypothesis and have found inconsistent results regarding oxytocin system activity and OCD. We investigated whether salivary oxytocin concentrations differed between children and adolescents with and without OCD and qualified our comparative analysis by investigating the possible covariates age, pubertal stage, and sex. Participants included 113 children and adolescents (8-17 years) with OCD and 88 children and adolescents without any previous or current psychiatric disorder and their parents (254 parents included). Salivary oxytocin concentrations were measured in children and parents with enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using frequentist and Bayesian approaches. We found no evidence of a difference in mean salivary oxytocin concentrations between children and adolescents with and without OCD. Bayesian analysis indicated anecdotal to moderate support for the null hypothesis. We found an association between oxytocin and age and between oxytocin and pubertal stage, which by visual inspection of plots and post-hoc tests indicated nonlinear relationships. We found no association between oxytocin concentration and sex. Our findings do not suggest elevated oxytocin concentrations in pediatric OCD. Nonlinear changes in oxytocin across development show the importance of accounting for hormonal and behavioral changes during puberty., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population's yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m 2 , respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p < 0.001, p < 0.001, respectively). Ultimately, telomere trajectories were associated with 1 year weight gain and increases in CRP levels, with telomere shortening strongly enhanced by BMI increments among patients receiving weight-inducing psychotropic treatments., Competing Interests: Competing interests CBE received honoraria for conferences from Forum pour la formation médicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor-Pharma, andZeller in the past 3 years. The authors declare no competing interests. Ethics This study was carried out in accordance with the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Vaud (CER-VD)., (© 2024. The Author(s).)

Aim: We aim to give an insight into the current situation in Switzerland concerning the pathways to care of young people with clinical high risk of psychosis. In a second step we propose a procedure of optimizing pathways to care developed within the project PsyYoung., Methods: A qualitative survey derived and adapted from Kotlicka-Antczak et al. (2020) was conducted in large early detection services of three Swiss cantons (Geneva, Basel-Stadt, Vaud) focusing on pathways to care. More specifically, using questionnaires delivered to the heads of participating services, information was collected on referral sources, on activities to implement outreach campaigns and on the use of a pre-screening tool., Results: Main results on referral source indicated that sources were variable but seemed to come primarily from the medical sector and more so from the psychiatric sector. Very few referrals came from non-medical sectors. Outreach activities included the contact to other clinics as well as through brochures and posters. All services but one used the Prodromal Questionnaire - 16 as pre-screening tool., Conclusions: All in all, the results indicate a referral and care pathway system implemented mostly within the medical and particularly mental health sector. Accordingly, the PsyYoung project proposes a procedure for pathways to care which could help overcome the obstacle of referrals being restrained to a narrow field of mental health and to harmonize the referral process within services dedicated to the same aim of helping young people at high risk of developing a psychosis., (© 2024 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: It is known that impairments in linguistic ability and motor function tend to co-occur in children, and that children from families with parental mental illness such as schizophrenia tend to perform poorly in both domains, but the exact nature of these links has not yet been fully elucidated., Design: In this study, we leveraged the first wave of the Danish High Risk and Resilience Study (VIA 7), which includes both genetic data and measures covering multiple developmental domains. The VIA 7 cohort comprises 522 7-year-old children born to parents with schizophrenia (N = 202), bipolar disorder (N = 120) or neither (N = 200). We investigated the relationships between linguistic ability and motor function using correlation and regression analyses, focusing on developmental coordination disorder (DCD) and specific language impairment (SLI) and their potential associations with the three risk groups., Results: We found significant correlations between most measures of language and motor function and significant associations of DCD and SLI with language and movement measures, respectively, the largest effect being that of DCD on receptive language, with a significant interaction effect: DCD was associated with poorer performance in children from schizophrenia families compared to bipolar disorder and control families. Both disorders showed higher prevalence among children with familial high risk of mental illness. We did not find significant evidence of genetic overlap between DCD and SLI., Conclusions: Our results suggest strong links between the domains of motor function and linguistic ability. Children of parents with schizophrenia are at high risk of comorbid language and movement disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Among youths, pathological irritability is highly prevalent and severely disabling. As a frequent symptom, it often leads to referrals to child and adolescent mental health services. Self-regulatory control (SRC) processes are a set of socio-psycho-physiological processes that allow individuals to adapt to their ever-changing environments. This conceptual framework may enhance the current understanding of the cognitive, emotional, behavioural and social dysregulations underlying irritability. The present systematic review (PROSPERO registration: #CRD42022370390) aims to synthesize existing studies that examine irritability through the lens of SRC processes among youths (< 18 years of age). We conducted a comprehensive literature search among six bibliographic databases: Embase.com, Medline ALL Ovid, APA PsycInfo Ovid, Web of Science Core Collection, the Cochrane Database of Systematic Reviews Wiley and ProQuest Dissertations & Theses A&I. Additional searches were performed using citation tracing strategies. The retrieved reports totalled 2612, of which we included 82 (i.e., articles) from 74 studies. More than 85% of reports were published during the last 6 years, highlighting the topicality of this work. The studies sampled n = 26,764 participants (n = 12,384 girls and n = 12,905 boys, n = 1475 no information) with an average age of 8.08 years (SD = 5.26). The included reports suggest that irritability has an association with lower effortful control, lower cognitive control and delay intolerance. Further, evidence indicates both cross-sectional and longitudinal associations between irritability and a lack of regulation skills for positive and negative emotions, particularly anger. Physiological regulation seems to moderate the association between irritability and psychopathology. Finally, the mutual influence between a child's irritability and parenting practice has been established in several studies. This review uses the lens of SRC to illustrate the current understanding of irritability in psychopathology, discusses important gaps in the literature, and highlights new avenues for further research., (© 2024. The Author(s).)

Individuals with schizophrenia (SZ) or bipolar disorder (BP) display cognitive impairments, while their first-degree relatives perform at an intermediate level between the patient groups and controls. However, the environmental impact of having an ill relative likely varies with the type of kinship and some studies suggest that offspring may be particularly disadvantaged. The present study aimed to investigate the relationship between parent and child cognition in parents with SZ or BD and their 7-year-old offspring. A population-based cohort of 522 children (parental SZ, n = 202; parental BP, n = 120; controls, n = 200) and their parents underwent the same assessment battery covering a wide range of cognitive functions. We used Bayesian statistics to model performance. We found that performance on non-verbal tests was better in offspring than parents with SZ or BP, using the controls as reference. However, for verbal tests, there was little to no evidence for this pattern or even some evidence for the opposite in the BP group: relatively better performance in parents than offspring. The findings suggest that the offspring of parents with SZ or BP may be particularly disadvantaged in verbal abilities. Future studies will show whether this pattern persists throughout development., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Clinical high risk for psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness. A potential compensatory strategy is to use estimates of individual pretest risk as a 'gatekeeper' for specialized assessment. We aimed to test a risk stratification model previously developed in London, UK (OASIS) and to train a new predictive model for the Swiss population., Method: The sample was composed of 513 individuals referred for CHR assessment from six Swiss early psychosis detection services. Sociodemographic variables available at referral were used as predictors whereas the outcome variable was transition to psychosis., Results: Replication of the risk stratification model developed in OASIS resulted in poor performance (Harrel's c=0.51). Retraining resulted in moderate discrimination (Harrel's c=0.67) which significantly differentiated between different risk groups. The lowest risk group had a cumulative transition incidence of 6.4% (CI: 0-23.1%) over two years., Conclusion: Failure to replicate the OASIS risk stratification model might reflect differences in the public health care systems and referral structures between Switzerland and London. Retraining resulted in a model with adequate discrimination performance. The developed model in combination with CHR assessment result, might be useful for identifying individuals with high pretest risk, who might benefit most from specialized intervention., (Copyright © 2024 The Author(s). Published by Elsevier España S.L.U. All rights reserved.)

Non-suicidal self-injury (NSSI) is an increasing mental health issue among adolescents. General practitioners and pediatricians play a crucial role in detecting, evaluating, and managing these behaviors. This article aims to provide recommendations for the first line surrounding the young person, such as the appropriate stance to adopt and the use of a safety plan, for effectively managing NSSI patients. It takes into account the often-present interpersonal hypersensitivity in these patients and includes strategies for working with families and within a multidisciplinary network., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Schizophrenia and bipolar disorder are characterized by social cognitive impairments, and recent research has identified alterations of the social brain. However, it is unknown whether familial high risk (FHR) of these disorders is associated with neurobiological alterations already present in childhood., Methods: As part of the Danish High Risk and Resilience Study-VIA 11, we examined children at FHR of schizophrenia (n = 121, 50% female) or bipolar disorder (n = 75, 47% female) and population-based control children (PBCs) (n = 128, 48% female). Using functional magnetic resonance imaging and dynamic causal modeling, we investigated brain activation and effective connectivity during the social cognition paradigm from the Human Connectome Project., Results: We found similar activation of the mentalizing network across groups, including visual area V5, the dorsomedial prefrontal cortex, and the posterior superior temporal sulcus (pSTS). Nonetheless, both FHR groups showed aberrant brain connectivity in the form of increased feedforward connectivity from left V5 to pSTS compared with PBCs. Children at FHR of schizophrenia had reduced intrinsic connectivity in bilateral V5 compared with PBCs, whereas children at FHR of bipolar disorder showed increased reciprocal connectivity between the left dorsomedial prefrontal cortex and the pSTS, increased intrinsic connectivity in the right pSTS, and reduced feedforward connectivity from the right pSTS to the dorsomedial prefrontal cortex compared with PBCs., Conclusions: Our results provide first-time evidence of aberrant brain connectivity in the mentalizing network of children at FHR of schizophrenia or FHR of bipolar disorder. Longitudinal research is warranted to clarify whether aberrant brain connectivity during mentalizing constitutes an endophenotype associated with the development of a mental disorder later in life., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Weight gain, blood lipids and/or glucose dysregulation can follow aripiprazole treatment onset. Whether aripiprazole dosage is associated with an increase in these metabolic parameters remains uncertain. The present study investigates aripiprazole dose associations with weight change, blood glucose, lipids, and blood pressure., Methods: 422 patients taking aripiprazole for a minimum of three weeks to one year were selected from PsyMetab and PsyClin cohorts. Associations between aripiprazole dose and metabolic outcomes were examined using linear mixed-effect models., Results: Aripiprazole dose was associated with weight change when considering its interaction with treatment duration (interaction term: -0.10, p < 0.001). This interaction resulted in greater weight gain for high versus low doses at the beginning of the treatment, this result being overturned at approximately five months, with greater weight increase for low versus high doses thereafter. LDL and HDL cholesterol levels were associated with aripiprazole dose over five months independently of treatment duration, with an average of 0.06 and 0.02 mmol/l increase for each 5 mg increment, respectively (p = 0.033 and p = 0.016, respectively). Furthermore, mean dose increases were associated with greater odds (+30 % per 5 mg increase) of clinically relevant weight gain (i.e., ≥7 %) over one year (p = 0.025)., Conclusion: Aripiprazole dose was associated with one-year weight changes when considering its interaction with treatment duration. Increasing its dose could lead to metabolic worsening over the first five months of treatment, during which minimum effective doses should be particularly preferred., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest in relation to the content of this work. Disclosure CBE received honoraria for conferences from Forum pour la formation médicale, Idorsia, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Takeda, Vifor-Pharma, and Zeller in the past 3 years., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year., Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants., Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume., Conclusions: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Atypical neurocognitive functioning has been found in adult patients with obsessive-compulsive disorder (OCD). However, little work has been done in children and adolescents with OCD. In this study, we investigated neurocognitive functioning in a large and representative sample of newly diagnosed children and adolescents with OCD compared to non-psychiatric controls. Children and adolescents with OCD (n = 119) and non-psychiatric controls (n = 90) underwent psychopathological assessment, intelligence testing, and a neurocognitive test battery spanning cognitive flexibility, planning and decision-making, working memory, fluency, and processing speed. The MANOVA main effect revealed that children and adolescents with OCD performed significantly worse than the control group (p < .001, η p 2 = 0.256). Atypical patient performance was particularly found for indices of cognitive flexibility, decision-making, working memory, and processing speed. We found no evidence of differences in planning or fluency. Moreover, we found no significant associations between neurocognitive performance and OCD symptom severity or comorbidity status. Our results indicate that children and adolescents with OCD show selective atypical neurocognitive functioning. These difficulties do not appear to drive their OCD symptoms. However, they may contribute to lifespan difficulties and interfere with treatment efficacy, an objective of our research currently., (© 2023. The Author(s).)

Objectives: This systematised review aimed to examine European literature reporting data about adaptative skills and global external functioning of unaccompanied minors (UAMs)., Methods: We conducted a systematised screening of four databases (APA PsycINFO Ovid, Medline Ovid ALL, Embase.com and Web Of Science Core Collection) using a research strategy including social, scholarly and behavioural abilities as well as externalising problems associated with the target population of UAMs. Thirty articles were included using pre-defined inclusion and exclusion criteria., Results: Our review showed that despite high levels of internalising disorders, socio-behavioural and educational adjustment of UAMs remained positive. It demonstrated how this population displays a strong desire for academic success and prosocial behaviours instead of aggressivity in everyday life. Nevertheless, our review drew attention to the strong tendency of UAMs to internalise their disorders and display chronic distress and problematic behaviours which increased with time spent in the host country., Conclusion: Our study draws attention to the risk of underestimating the real mental health needs of refugees, due to preserved external functioning combined with significant settlement pressures., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Prod’hom, Rosselet Amoussou, Plessen, Cuissart de Grelle and Gaultier.)

Adolescence is a time of increased vulnerability to mental health conditions, which may necessitate hospitalization. This study sought to identify and characterize patterns of adolescent (re-)hospitalizations. The one-year (re-)hospitalization patterns of 233 adolescents were analyzed. The sequences of hospitalization and discharge was examined using cluster analyses. Results revealed five distinct (re-)hospitalization patterns or clusters: Cluster A represented brief hospitalizations with 56 cases (24.03%) averaging 7.71 days; cluster B consisted of repetitive short hospitalizations involving 97 cases (41.63%) with an average of 19.90 days; cluster C encompassed repetitive medium hospitalizations included 66 cases (28.33%) averaging 41.33 days; cluster D included long hospitalizations with 11 cases (4.72%) and an average of 99.36 days; cluster E depicted chronic hospitalizations, accounting for 3 cases (1.29%) with an average stay of 138.67 days. Despite no age-based differences across clusters, distinctions were noted in terms of sex, diagnoses, and severity of clinical and psychosocial difficulties. The study identified characteristics of both regular and atypical adolescent hospitalization users, emphasizing the distribution of hospitalization days and their associated clinical attributes. Such insights are pivotal for enhancing the organization of child and adolescent mental health services to cater to the growing care requirements of this age group., (© 2024. The Author(s).)

Background: Therapeutic drug monitoring (TDM) is strongly recommended for olanzapine due to its high pharmacokinetic variability. This study aimed to investigate the impact of various clinical factors on olanzapine plasma concentrations in patients with psychiatric disorders., Methods: The study used TDM data from the PsyMetab cohort, including 547 daily dose-normalized, steady-state, olanzapine plasma concentrations (C:D ratios) from 248 patients. Both intrinsic factors (eg, sex, age, body weight) and extrinsic factors (eg, smoking status, comedications, hospitalization) were examined. Univariate and multivariable, linear, mixed-effects models were employed, with a stepwise selection procedure based on Akaike information criterion to identify the relevant covariates., Results: In the multivariable model (based on 440 observations with a complete data set), several significant findings emerged. Olanzapine C:D ratios were significantly lower in smokers (β = -0.65, P < 0.001), valproate users (β = -0.53, P = 0.002), and inpatients (β = -0.20, P = 0.025). Furthermore, the C:D ratios decreased significantly as the time since the last dose increased (β = -0.040, P < 0.001). The male sex had a significant main effect on olanzapine C:D ratios (β = -2.80, P < 0.001), with significant interactions with age (β = 0.025, P < 0.001) and body weight (β = 0.017, P = 0.011). The selected covariates explained 30.3% of the variation in C:D ratios, with smoking status accounting for 7.7% and sex contributing 6.9%. The overall variation explained by both the fixed and random parts of the model was 67.4%. The model facilitated the prediction of olanzapine C:D ratios based on sex, age, and body weight., Conclusions: The clinical factors examined in this study, including sex, age, body weight, smoking status, and valproate comedication, remarkably influence olanzapine C:D ratios. Considering these factors, in addition to TDM and the clinical situation, could be important for dose adjustment., Competing Interests: Over the past 3 years, N. Ansermot has been awarded honoraria for a conference by Sysmex Suisse AG. S. Crettol has earned honoraria for conducting CME courses on behalf of Forum pour la formation médicale, Barr, Switzerland, and has provided consultancy services for the Swiss Health Observatory (Obsan) under the Swiss Federal Office of Public Health. F. Vandenberghe has received honoraria for delivering CME courses through Forum pour la formation médicale, Barr, Switzerland, in addition to CME courses for the Swiss Association of Public Health Administration and for a conference organized by Sysmex Suisse AG. C. B. Eap was honored with honoraria for his participation in conferences sponsored by Forum pour la formation médicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor-Pharma, and Zeller within the same time frame. No declarations were made by the remaining authors. The authors affirm no conflicts of interest concerning the content of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Psychiatrists play a crucial role in evaluating requests and treatment indications for individuals experiencing gender incongruence, while also providing support throughout the transition process. Their work involves addressing both the psychological and somatic aspects of this journey, facilitating the profound identity changes it entails., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background and Hypotheses: Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children., Study Design: Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study-VIA 11., Study Results: We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in the analyses. Executive control effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRT in FHR-BP and FHR-SZ compared to PBC (BF10 = 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post hoc analyses excluding children with psychiatric illness yielded same results., Conclusion: FHR-SZ and FHR-BP at age 11-12 show intact ability to resolve a spatial visuomotor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Objective: The aim of this study was to evaluate valproate dose association with weight change, blood glucose, lipid levels, and blood pressure in a psychiatric population., Methods: Data from 215 patients taking valproate for up to 1 year were collected from 2 longitudinal studies that monitored metabolic variables between 2007 and 2022. Linear mixed-effect models and logistic regressions were used to analyze the associations between valproate doses and metabolic outcomes., Results: An increase in valproate dose of 500 mg was associated with a weight change of +0.52% per month over a year ( P  < .001). The association between valproate dose and weight change was evident both before and after 3 months of treatment. Weight increase was greater for treatment durations of < 3 months compared to ≥ 3 months (+0.56%, P  < .001 and +0.12%, P  = .02 per month, respectively). Using piecewise regression, a significant association between dose and weight gain was observed in patients receiving doses equal to or above the median dose (1,300 mg/d), with a +0.50% increase in weight for each dose increment of 500 mg ( P  = .004). Among men, each 500 mg dose increment was associated with weight increases of +0.59% per month ( P  = .004), whereas a trend was observed for women (+0.40%, P  = .09). No associations were found between valproate doses and blood glucose, lipid levels, or blood pressure over a 6-month treatment period., Conclusions: This study provides evidence that valproate dose, mainly for doses at or above 1,300 mg/d, is associated with weight gain in psychiatric patients, suggesting that the lowest effective doses should be prescribed to minimize weight gain., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Over half of children with Attention-Deficit/Hyperactivity Disorder (ADHD) display interpersonal and social problems. Several lines of research suggest that suboptimal decision making, the ability to adjust choices to different risk-varying options, influences poorer choices made in social interactions. We thus measured decision making and its prediction of social problems longitudinally with the Cambridge Gambling Task in children with ADHD over four years. Children with ADHD had shown suboptimal decision making driven mainly by delay aversion at baseline and we expected this to be a stabile trait which would predict greater parent-reported social problems. From the baseline assessment (n = 70), 67% participated at the follow-up assessment, 21 from the ADHD group and 26 from the typically developing group. The mean age at the follow-up was 14.5 years old. The results confirmed our expectations that suboptimal decision making was a stabile trait in children and adolescents with ADHD. Although delay aversion did not differ from controls at follow-up it still proved to be the main longitudinal predictor for greater social problems. Our findings indicate that impulsivity in social interactions may be due to a motivational deficit in youth with ADHD., (© 2024. The Author(s).)

Background: Metabolic side effects of psychotropic medications are a major drawback to patients' successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip., Results: A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10 -16 ) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10 -8 ) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10 -8 ), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association)., Conclusion: These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role., (© 2024. The Author(s).)

This study investigates early onset of treatment response as predictor of symptomatic and functional outcome 3 years after initiation of methylphenidate (MPH) administration in a naturalistic, clinical cohort of children and adolescents with ADHD. Children were followed across an initial 12-week MPH treatment trial and after 3 years, with ratings of symptoms and impairment. Associations between a clinically significant MPH treatment response in week 3 (defined as ≥ 20% reduction in clinician-rated symptoms) and in week 12 (defined as ≥ 40% reduction), and 3-year outcome were tested in multivariate linear regression models, adjusting for sex, age, comorbidity, IQ, maternal education, parental psychiatric disorder, and baseline symptoms and function. We did not have information on treatment adherence or the nature of treatments beyond 12 weeks. 148 children, mean age 12.4 years (range 10-16 years), 77% males, participated in the follow-up. We found a significant decrease in symptom score from baseline [M = 41.9 (SD = 13.2)] to 3-year follow-up [M = 27.5 (SD = 12.7), p < 0.001, and in impairment score from baseline (M = 41.6 (SD = 19.4)] to 3-year follow-up [M = 35.6 (SD = 20.2), p = 0.005]. Treatment responses in week 3 and week 12 were significant predictors of the long-term outcome of symptoms, but not of impairment at 3-year follow-up, when adjusting for other well-known predictors. Early treatment response predicts long-term outcome over and above other well-known predictors. Clinicians should follow-up patients carefully, during the first months of treatment, and detect non-responders, since there might be a window of opportunity to alter the outcome, by changing the treatment strategy.Clinical trial registration: ClinicalTrials.gov, registration number NCT04366609, April 28, 2020 retrospectively registered., (© 2023. The Author(s).)

Background & Objectives: Terror catastrophizing, defined as an ongoing fear of future terrorist attacks, is associated with a higher incidence of anxiety disorders, among other psychological impacts. However, previous studies examining terror catastrophizing's relationship to other mental health disorders are limited. The current study sought to determine if patients diagnosed with anxiety and depression would experience increased terror catastrophizing. Additionally, this study aimed to investigate whether parental terror catastrophizing increases children's internalizing symptoms. Design & Methods: Individuals were randomly drawn from the Danish Civil Registration System and invited to complete a series of questionnaires to measure terror catastrophizing tendency, lifetime parental trauma, and children's internalizing symptoms. In total, n  = 4,175 invitees completed the survey of which 933 reported on a child between 6 and 18 years. Responses were analyzed using a generalized linear regression model. Results: Participants diagnosed with anxiety alone or comorbid with depression were more likely to experience symptoms of terror catastrophizing than undiagnosed participants ( β  = 0.10, p  < .001; β  = 0.07, p  = .012). Furthermore, the parental tendency to catastrophize terror was associated with higher internalizing symptoms in children ( β  = 0.09, p  = .006), even after taking parental diagnoses, as well as lifetime and childhood trauma into account. Conclusion: The results can inform clinical practices to account for a patient's potential to exhibit increased terror catastrophizing tendencies or be more affected by traumatic events. Additionally, they can offer insights for designing novel preventative interventions for the whole family, due to the relation between parental tendencies for terror catastrophizing and the internalizing symptoms observed in children.

Background and Hypothesis: Individuals with schizophrenia or bipolar disorder have attenuated auditory mismatch negativity (MMN) responses, indicating impaired sensory information processing. Computational models of effective connectivity between brain areas underlying MMN responses show reduced connectivity between fronto-temporal areas in individuals with schizophrenia. Here we ask whether children at familial high risk (FHR) of developing a serious mental disorder show similar alterations., Study Design: We recruited 67 children at FHR for schizophrenia, 47 children at FHR for bipolar disorder as well as 59 matched population-based controls from the Danish High Risk and Resilience study. The 11-12-year-old participants engaged in a classical auditory MMN paradigm with deviations in frequency, duration, or frequency and duration, while we recorded their EEG. We used dynamic causal modeling (DCM) to infer on the effective connectivity between brain areas underlying MMN., Study Results: DCM yielded strong evidence for differences in effective connectivity among groups in connections from right inferior frontal gyrus (IFG) to right superior temporal gyrus (STG), along with differences in intrinsic connectivity within primary auditory cortex (A1). Critically, the 2 high-risk groups differed in intrinsic connectivity in left STG and IFG as well as effective connectivity from right A1 to right STG. Results persisted even when controlling for past or present psychiatric diagnoses., Conclusions: We provide novel evidence that connectivity underlying MMN responses in children at FHR for schizophrenia and bipolar disorder is altered at the age of 11-12, echoing findings that have been found in individuals with manifest schizophrenia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

The purpose of this naturalistic, prospective study was to identify risk factors for mood disorders in offspring of parents with bipolar disorder (BPD) using the discordant-sibling design by comparing premorbid psychopathology or symptoms, temperament, personality traits and coping style as well as the perception of family-related characteristics among affected and unaffected siblings within the same family. This approach controls for confounding by unmeasured genetic and environmental factors shared within families. Our sample comprised 24 families of a parent with BPD with at least one child that developed BPD or major depressive disorder (n = 31), and at least one child who did not. Offspring were followed for a mean duration of 16.2 (s.d: 4.6) years. Information was collected from the offspring themselves. Generalized linear mixed models only revealed differences in three dimensions of the Dimension of Temperament Survey-Revised (DOTS-R) version: Offspring with mood disorders scored higher on "Approach-withdrawal", "Rhythmicity for daily habits", and "Task orientation" than their unaffected siblings. The higher scores, and not lower scores as expected, on these temperament dimensions observed in offspring that subsequently developed mood disorders may reflect increased vulnerability, but they could also mirror premorbid mood swings or strategies to cope with them., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)