The INNODIA Type 1 Diabetes Natural History Study: a European cohort of newly diagnosed children, adolescents and adults.

AIMS/HYPOTHESIS: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual's clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis. METHODS: Data were collected from the large INNODIA cohort of individuals (aged 1.0-45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10-17 years; and ≥18 years. RESULTS: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0-382.0) pmol/l (AUC 749.3 [466.2-1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001). CONCLUSIONS/INTERPRETATION: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline.

A Federated Database for Obesity Research: An IMI-SOPHIA Study.

Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders.

Pinpointing change in virtual reality assisted treatment for violent offenders: a pilot study of Virtual Reality Aggression Prevention Training (VRAPT).

Preventing relapse into violence and its destructive consequences among persistent re-offenders is a primary concern in forensic settings. The Risk-Need-Responsivity framework models the best current practice for offender treatment, focused on building skills and changing pro-criminal cognitions. However, treatment effects are often modest, and the forensic context can obstruct the delivery of interventions. Developing treatments for offenders should focus on the best method of delivery to make "what works work." Virtual reality (VR)-assisted treatments such as Virtual Reality Aggression Prevention Training (VRAPT) are a new and innovative approach to offender treatment. This pilot study followed 14 male violent offenders who participated in VRAPT in a Swedish prison context and measured changes from pre-treatment to post-treatment and 3-month follow-up in targeted aggression, emotion regulation, and anger. It also investigated potential impact factors (pro-criminal cognitions, externalizing behaviors, psychosocial background, and childhood adverse experiences). In Bayesian linear mixed effects models, participants showed a high probability of change from pre-treatment to post-treatment and to follow-up on all outcome measures. All outcome measures demonstrated a low probability of change from post-treatment to follow-up. Analysis of reliable change showed that participants' results ranged from recovery to deterioration. We discuss the implications of the study for VRAPT's impact on the target group, those who might benefit from the approach, and suggested foci for future studies in the field of VR-assisted offender treatment. The study was preregistered at the International Standard Randomized Controlled Trial Number registry (https://doi.org/10.1186/ISRCTN14916410).

Improving the stability of bivariate correlations using informative Bayesian priors: a Monte Carlo simulation study.

Objective: Much of psychological research has suffered from small sample sizes and low statistical power, resulting in unstable parameter estimates. The Bayesian approach offers a promising solution by incorporating prior knowledge into statistical models, which may lead to improved stability compared to a frequentist approach. Methods: Simulated data from four populations with known bivariate correlations (ρ = 0.1, 0.2, 0.3, 0.4) was used to estimate the sample correlation as samples were sequentially added from the population, from n = 10 to n = 500. The impact of three different, subjectively defined prior distributions (weakly, moderately, and highly informative) was investigated and compared to a frequentist model. Results: The results show that bivariate correlation estimates are unstable, and that the risk of obtaining an estimate that is exaggerated or in the wrong direction is relatively high, for sample sizes for below 100, and considerably so for sample sizes below 50. However, this instability can be constrained by informative Bayesian priors. Conclusion: Informative Bayesian priors have the potential to significantly reduce sample size requirements and help ensure that obtained estimates are in line with realistic expectations. The combined stabilizing and regularizing effect of a weakly informative prior is particularly useful when conducting research with small samples. The impact of more informative Bayesian priors depends on one's threshold for probability and whether one's goal is to obtain an estimate merely in the correct direction, or to obtain a high precision estimate whose associated interval falls within a narrow range. Implications for sample size requirements and directions for future research are discussed.

Exploring the psychometric properties of the externalizing spectrum inventory-brief form in a Swedish forensic psychiatric inpatient sample.

BACKGROUND: The Externalizing Spectrum Inventory-Brief Form (ESI-BF) [1] is a 160-item self-report instrument designed for the assessment of externalizing psychopathology, yet few studies to date have evaluated its psychometric properties, structural fit, and criterion validity in forensic psychiatric settings. METHODS: Here, we investigated these aspects in a sample of forensic psychiatric inpatients (n = 77) from a maximum-security forensic psychiatric hospital in Sweden. We firstly investigated the reliability. Secondly, using confirmatory factor analysis, the structure of the ESI-BF. And thirdly, using a Bayesian approach, assessed how the three ESI-BF subfactors relate to criterion measures of antisocial behaviors, substance use, and lifetime externalizing spectrum diagnoses. RESULTS: The ESI-BF demonstrated good to adequate reliability and internal consistency, with all but four facet scales exhibiting α and ω values ≥ 0.80. Average inter-item correlations for the facet scales ranged from 0.31 to 0.74. However, all structural models exhibited poor to mediocre fit, with model fit values for the CFI being 0.66, 0.79 and 0.87 and RMSEA values of 0.14, 0.12 and 0.09. for the unidimensional correlated factors and bifactor model, respectively. Regarding criterion validity, all subscales of the item-based ESI-BF three-factor model exhibited robust correlations with the Life History of Aggression total, aggression and antisocial/consequences subscales, with correlations ranging from 0.29 to 0.55. All ESI-BF subfactors demonstrated robust associations, yet with different externalizing outcomes, lending tentative support to its criterion validity. CONCLUSION: Despite remaining ambiguities regarding its structural fit, the ESI-BF may be promising for assessing externalizing psychopathology in forensic psychiatric populations. However, further investigation of the ESI-BF is needed before any firm conclusions can be drawn about its appropriateness in forensic psychiatric settings.

Gender Differences and Associated Factors Influencing Problem Gambling in Adolescents in Sweden: Cross-sectional Investigation.

BACKGROUND: Although gambling disorder is traditionally considered an adult phenomenon, the behavior usually begins in childhood or adolescence. OBJECTIVE: The aim of this study was to explore the frequency of problem gambling among Swedish adolescents and the suspected associated factors. METHODS: This study was based on data collected through a public health survey distributed in 2016 to pupils in ninth grade of primary school and in second grade of secondary school in Sweden. Bayesian binomial regression models, with weakly informative priors, were used to examine whether the frequency of the associated factors differed between those with and without problem gambling. RESULTS: Approximately 11.7% (469/4002) of the boys in ninth grade of primary school and 13.9% (472/3407) of the boys in second grade of secondary school were classified as problem gamblers. For girls, the corresponding frequencies were 1.2% (48/4167) and 0.7% (27/3634), respectively. The overall response rate was 77% (9143/11,868) among ninth grade pupils and 73.4% (7949/10,832) among second grade pupils, resulting in a total of 17,092 responses. Problem gambling was associated with poor sleep and having tried smoking, alcohol, and other substances among both boys and girls in ninth grade of primary school and boys in second grade of secondary school. Problem gambling among girls in second grade of secondary school was associated with an increased prevalence of having tried smoking and other substances and an increased prevalence of poor sleep. CONCLUSIONS: Using a large representative sample of Swedish adolescents, we found that problem gambling was robustly associated with a substantially increased prevalence of poor sleep and having tried smoking, alcohol, and other substances among both boys and girls in ninth grade of primary school as well as among boys in second grade of secondary school. Our study adds important information for policy makers pointing at vulnerable groups to be considered in their work to prevent problem gambling.

Prolonged NoGo P3 latency as a possible neurobehavioral correlate of aggressive and antisocial behaviors: A Go/NoGo ERP study.

Aggressive and antisocial behaviors are detrimental to society and constitute major challenges in forensic mental health settings, yet the associated neural circuitry remains poorly understood. Here, we investigated differences in aggressive and antisocial behaviors between healthy controls (n = 20) and violent mentally disordered offenders (MDOs; n = 26), and examined associations between aggressive and antisocial behaviors, behavioral inhibitory control, and neurophysiological activity across the whole sample (n = 46). Event-related potentials were obtained using EEG while participants completed a Go/NoGo response inhibition task, and aggressive and antisocial behaviors were assessed with the Life History of Aggression (LHA) instrument. Using a robust Bayesian linear regression approach, we found that MDOs scored substantially higher than healthy controls on LHA Aggression and Antisocial subscales. Using the whole sample and after adjusting for age, we found that scores on the LHA Aggression and Antisocial subscales were robustly associated with longer NoGo P3 latency, and less robustly with longer NoGo N2 latency. Post-hoc analyzes suggested that healthy controls and MDOs exhibited similar associations. With several limitations in mind, we suggest that prolonged NoGo P3 latency, reflecting decreased neural efficiency during the later stages of conflict monitoring or outcome evaluation, is a potential neurobehavioral correlate of aggressive and antisocial behaviors.

Gender-Based Differences and Associated Factors Surrounding Excessive Smartphone Use Among Adolescents: Cross-sectional Study.

BACKGROUND: Excessive smartphone use is a new and debated phenomenon frequently mentioned in the context of behavioral addiction, showing both shared and distinct traits when compared to pathological gaming and gambling. OBJECTIVE: The aim of this study is to describe excessive smartphone use and associated factors among adolescents, focusing on comparisons between boys and girls. METHODS: This study was based on data collected through a large-scale public health survey distributed in 2016 to pupils in the 9th grade of primary school and those in the 2nd grade of secondary school. Bayesian binomial regression models, with weakly informative priors, were used to examine whether the frequency of associated factors differed between those who reported excessive smartphone use and those who did not. RESULTS: The overall response rate was 77% (9143/11,868) among 9th grade pupils and 73.4% (7949/10,832) among 2nd grade pupils, resulting in a total of 17,092 responses. Based on the estimated median absolute percentage differences, along with associated odds ratios, we found that excessive smartphone use was associated with the use of cigarettes, alcohol, and other substances. The reporting of anxiety and worry along with feeling low more than once a week consistently increased the odds of excessive smartphone use among girls, whereas anxiety and worry elevated the odds of excessive smartphone use among boys. The reporting of less than 7 hours of sleep per night was associated with excessive smartphone use in all 4 study groups. CONCLUSIONS: The results varied across gender and grade in terms of robustness and the size of estimated difference. However, excessive smartphone use was associated with a higher frequency of multiple suspected associated factors, including ever having tried smoking, alcohol, or other substances; poor sleep; and often feeling low and feeling anxious. This study sheds light on some features and distinctions of a potentially problematic behavior among adolescents.

A cross-sectional study on extensive gaming in adolescents.

BACKGROUND: Extensive gaming and the consequences thereof is frequently reported from child and adolescent psychiatry and school health care. The behavior is associated with compulsion, psychiatric and physical symptoms, impaired cognitive development and poorer school performance. This phenomenon has been described as an emergent health issue for men and little is known about its potential gender-specific characteristics. The aim of this study was to explore extensive gaming among male and female adolescents and to investigate whether the frequency of often feeling low, often feeling anxious, self-reported ADHD, self-reported ASD, being satisfied with one's own general health, poor sleep, loneliness, and having tried smoking, alcohol, and/or other substances differed among those with and without extensive gaming. DESIGN AND METHODS: This study was based on data collected through a public health survey distributed in 2016 to pupils in 9th grade of primary school and in second grade of secondary school, including a total of 13498 participants. The association between extensive gaming and different factors was estimated among male and female respondents separately. RESULTS: Roughly 30% of the male and 5% of the female respondents were categorized as extensive gamers. Extensive gaming was associated with a higher prevalence of poor sleep and a lower prevalence of being satisfied with one's own health among boys and (to a higher degree) among girls. CONCLUSIONS: Altogether, our results contribute to the impression that extensive gaming is more heavily related to subjective health complaints among female than male adolescents.

Early onset externalizing behaviors among forensic psychiatric patients: Identification in child and adolescent psychiatric services.

Forensic psychiatric patients constitute a heterogeneous patient group, with common comorbidity within the externalizing spectrum. Increased knowledge on early antecedents in the pathway to severe mental illness and criminality is needed. In this study, we investigated early onset externalizing behaviors in three groups of forensic psychiatric patients 1) patients without contact with child and adolescent psychiatry (CAP), 2) patients with CAP contact, and 3) patients with both CAP contact and institutional placement. Participants (N = 98) were consecutively recruited from a cohort of forensic psychiatric patients in Sweden between 2016 and 2020. Data were collected through file information and semi-structured interviews and analyzed with a Bayesian approach. A history of CAP together with an institutional placement during childhood or adolescence was associated with more externalizing disorders, a higher number of convictions over the lifetime, a lower age at first conviction, and a lower age at first self-reported crime. Our findings provide further insight into the importance of early-onset adverse behaviors in the development of later externalizing behaviors, and may be of particular use for practitioners within social services and CAP services.

Structural Brain Correlates of the Externalizing Spectrum in Young Adults.

The externalizing spectrum, including traits and behaviors such as aggression, reduced inhibitiory control and substance abuse, is associated with altered prefrontal brain morphology. However, the degree to which different manifestations of the externalizing spectrum are associated with distinct or overlapping variations in individual brain morphology is unclear. Here, we therefore used structural magnetic resonance imaging, self-report assessment, and a response inhibition task in a sample of 59 young adults to examine how cortical thickness in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC) relate to four different manifestations of the externalizing spectrum: disinhibition, callous aggression, substance abuse, and behavioral inhibitory control. Using Bayesian linear regression models controlling for age, gender, and years of education, we found that the different manifestations of the externalizing spectrum were associated with both distinct and overlapping morphology variations. Specifically, both callous aggression and inhibitory control was associated with increased cortical thickness of the OFC, a region involved in reward processing, decision-making, and regulation of anxiety and fear. Both disinhibition and substance abuse were associated with DLPFC thickness, although with opposite association patterns, possibly reflecting processes related to inhibitory control, working memory and attention. Moreover, disinhibition, but not callous aggression or substance abuse, was associated with behavioral inhibitory control. Our results provide further support for the link between externalizing behaviors and prefrontal brain morphology, while identifying distinct prefrontal areas associated with different clinically relevant manifestations. These findings may help guide further research aimed at developing novel treatment and intervention strategies for externalizing behaviors and disorders.

Trait Disinhibition and NoGo Event-Related Potentials in Violent Mentally Disordered Offenders and Healthy Controls.

Trait disinhibition may function as a dispositional liability toward maladaptive behaviors relevant in the treatment of mentally disordered offenders (MDOs). Reduced amplitude and prolonged latency of the NoGo N2 and P3 event-related potentials have emerged as promising candidates for transdiagnostic, biobehavioral markers of trait disinhibition, yet no study has specifically investigated these two components in violent, inpatient MDOs. Here, we examined self-reported trait disinhibition, experimentally assessed response inhibition, and NoGo N2 and P3 amplitude and latency in male, violent MDOs (N = 27) and healthy controls (N = 20). MDOs had a higher degree of trait disinhibition, reduced NoGo P3 amplitude, and delayed NoGo P3 latency compared to controls. The reduced NoGo P3 amplitude and delayed NoGo P3 latency in MDOs may stem from deficits during monitoring or evaluation of behavior. NoGo P3 latency was associated with increased trait disinhibition in the whole sample, suggesting that trait disinhibition may be associated with reduced neural efficiency during later stages of outcome monitoring or evaluation. Findings for NoGo N2 amplitude and latency were small and non-robust. With several limitations in mind, this is the first study to demonstrate attenuated NoGo P3 amplitude and delayed NoGo P3 latency in violent, inpatient MDOs compared to healthy controls.

Corrigendum: Examining Associations Between Psychopathic Traits and Executive Functions in Incarcerated Violent Offenders.

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Exploring the Effects of an Acute Dose of Antipsychotic Medication on Motivation-mediated BOLD Activity Using fMRI and a Perceptual Decision-making Task.

The left inferior frontal gyrus and the bilateral ventral striatum are thought to be involved in motivation-mediated decision-making. Antipsychotics may influence this relationship, and atypical antipsychotics improve secondary negative symptoms in schizophrenia, such as loss of motivation, although the acute effects of pharmacological medication on motivation are not fully understood. In this single-blinded, randomized controlled trial, 49 healthy volunteers were randomized into three groups to receive a single dose of haloperidol, aripiprazole or placebo. Between 4.0 and 5.6 h later, participant's brain blood-oxygen-level dependent (BOLD) activity was recorded using functional magnetic resonance imaging (fMRI) while completing a perceptual decision-making fMRI task consisting of one neutral and one motivated condition. Response bias, reflecting the participant's willingness to say that the target stimulus is present, was calculated using signal detection theory. Concurrent with widespread changes in BOLD signal in the motivated vs. neutral condition, a less conservative, mathematically optimal response bias was observed in the motivated condition across the whole sample. Within-group differences in BOLD signal in the left inferior frontal gyrus and bilateral ventral striatum were observed between conditions in the aripiprazole and haloperidol groups, but not in the placebo group. No robust between-group differences in brain activity in the left inferior frontal gyrus or the bilateral ventral striatum were found. Overall, we found no robust evidence for an effect of either aripiprazole or haloperidol on motivationally mediated behavior. An interesting pattern of correlations possibly related to pharmacologically induced alterations in the dopamine system was observed, although findings remain inconclusive and must be replicated in larger samples.

Prediction of recidivism in a long-term follow-up of forensic psychiatric patients: Incremental effects of neuroimaging data.

One of the primary objectives in forensic psychiatry, distinguishing it from other psychiatric disciplines, is risk management. Assessments of the risk of criminal recidivism are performed on a routine basis, as a baseline for risk management for populations involved in the criminal justice system. However, the risk assessment tools available to clinical practice are limited in their ability to predict recidivism. Recently, the prospect of incorporating neuroimaging data to improve the prediction of criminal behavior has received increased attention. In this study we investigated the feasibility of including neuroimaging data in the prediction of recidivism by studying whether the inclusion of resting-state regional cerebral blood flow measurements leads to an incremental increase in predictive performance over traditional risk factors. A subsample (N = 44) from a cohort of forensic psychiatric patients who underwent single-photon emission computed tomography neuroimaging and clinical psychiatric assessment during their court-ordered forensic psychiatric investigation were included in a long-term (ten year average time at risk) follow-up. A Baseline model with eight empirically established risk factors, and an Extended model which also included resting-state regional cerebral blood flow measurements from eight brain regions were estimated using random forest classification and compared using several predictive performance metrics. Including neuroimaging data in the Extended model increased the area under the receiver operating characteristic curve (AUC) from .69 to .81, increased accuracy from .64 to .82 and increased the scaled Brier score from .08 to .25, supporting the feasibility of including neuroimaging data in the prediction of recidivism in forensic psychiatric patients. Although our results hint at potential benefits in the domain of risk assessment, several limitations and ethical challenges are discussed. Further studies with larger, carefully characterized clinical samples utilizing higher-resolution neuroimaging techniques are warranted.

Examining Associations Between Psychopathic Traits and Executive Functions in Incarcerated Violent Offenders.

Executive functions (EFs) are essential in almost all aspects of daily life and have been robustly related to antisocial behavior. However, the relationship between psychopathy and EFs has remained equivocal. Research investigating lower-level trait dimensions of psychopathy using standardized EF measures could be beneficial in addressing this issue. In this study, we examined associations between four EFs and four dimensions of psychopathic traits (interpersonal, affective, lifestyle, antisocial) using zero-order correlation and a combination of classical and Bayesian statistical methods. Two hundred and fourteen incarcerated male violent offenders were assessed with the Psychopathy Checklist-Revised and completed tests of cognitive flexibility, spatial working memory, response inhibition, and planning and problem-solving using the Cambridge Neuropsychological Test Automated Battery. Lifestyle psychopathic traits were significantly associated with reduced initial thinking time in a planning and problem-solving task, with a Bayes factor indicating substantial evidence for the observed correlation, and antisocial psychopathic traits showed a significant association with reduced initial thinking time in the same task, although the Bayes factor indicated only anecdotal evidence. Significant associations were also found between affective and antisocial psychopathic traits and less efficient strategic thinking in a spatial working memory task, and between affective, lifestyle and antisocial psychopathic traits and fewer problems solved in a planning and problem-solving task, although these findings were not corroborated by the Bayesian analysis. While the observed effects ranged between small and medium, our study suggests that reduced initial thinking times in planning and problem-solving is robustly associated with higher degrees of lifestyle and antisocial psychopathic traits.

Offenders in emerging adulthood: School maladjustment, childhood adversities, and prediction of aggressive antisocial behaviors.

Early psychosocial adversities and maladjustment, such as childhood maltreatment and school adjustment problems, have been linked to an increased risk of aggressive antisocial behaviors. Yet, clinical studies of subjects at the highest risk of persistence in such behaviors are rare, especially during the life-changing transition years of emerging adulthood. This study describes early predictors of aggressive antisocial behaviors in a large, nationally representative cohort of Swedish, male violent offenders in emerging adulthood (age range = 18-25 years; N = 270). First, data on psychosocial background characteristics and aggressive antisocial behaviors (including age at onset) are provided. Second, early predictors of aggressive antisocial behaviors are tested in bivariate and multivariate interactive models. The offenders demonstrated a diversity of early onset adversities and disruptive behaviors, in line with established risk factors for subsequent criminality and adverse outcomes in a variety of life domains. Severe school adjustment problems, especially bullying others and early onset truancy, were important and interrelated predictors of aggressive antisocial behaviors over the lifetime, whereas childhood adversities such as parental substance or alcohol abuse and repeated exposure to violence at home during childhood were interrelated predictors of aggressive antisocial behaviors, albeit with less statistical importance. The findings stress the importance of early identification of individuals in the risk zone of developing severe and persistent aggressive antisocial behaviors and of early preventive interventions directed toward families with high-risk profiles. The findings also provide initial guidelines on which psychosocial background risk factors that need to be considered first-hand in early interventions. (PsycINFO Database Record