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  • Patel, Yash, et al. (författare)
  • Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.
  • 2020
  • Ingår i: JAMA psychiatry. - 2168-6238.
  • Tidskriftsartikel (refereegranskat)abstract
    • Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.Interregional profiles of group difference in cortical thickness between cases and controls.A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
  • Dima, Danai, et al. (författare)
  • Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3–90 years
  • 2021
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193.
  • Tidskriftsartikel (refereegranskat)abstract
    • Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
  • Frangou, Sophia, et al. (författare)
  • Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years
  • 2021
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193.
  • Tidskriftsartikel (refereegranskat)abstract
    • Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
  • Wierenga, Lara M., et al. (författare)
  • Greater male than female variability in regional brain structure across the lifespan
  • 2020
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193.
  • Tidskriftsartikel (refereegranskat)abstract
    • For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
  • Krebs, G., et al. (författare)
  • The association between body dysmorphic symptoms and suicidality among adolescents and young adults: A genetically informative study
  • 2020
  • Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978.
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPrevious research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown.MethodsTwo independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages.ResultsSuicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively).ConclusionsBDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk. Copyright © The Author(s), 2020. Published by Cambridge University Press.
  • Aspvall, K., et al. (författare)
  • Effect of an Internet-Delivered Stepped-Care Program vs In-Person Cognitive Behavioral Therapy on Obsessive-Compulsive Disorder Symptoms in Children and Adolescents: A Randomized Clinical Trial
  • 2021
  • Ingår i: Jama-Journal of the American Medical Association. - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 325:18, s. 1863-1873
  • Tidskriftsartikel (refereegranskat)abstract
    • Key PointsQuestionIs internet-delivered cognitive behavioral therapy (CBT) implemented in a stepped-care model noninferior to in-person CBT for children and adolescents with obsessive-compulsive disorder? FindingsIn this randomized, noninferiority clinical trial, 152 children and adolescents with obsessive-compulsive disorder were treated with an internet-delivered CBT program followed by traditional in-person CBT if necessary vs in-person CBT alone. After 6 months, the mean Children's Yale-Brown Obsessive-Compulsive Scale score was 11.57 in those treated with internet-delivered CBT vs 10.57 in those treated with in-person CBT, a difference that met the noninferiority criterion of 4 points. MeaningTreating children and adolescents with obsessive-compulsive disorder with an internet intervention followed by traditional face-to-face therapy if necessary was noninferior to in-person therapy alone. ImportanceIn most countries, young people with obsessive-compulsive disorder have limited access to specialist cognitive behavioral therapy (CBT), a first-line treatment. ObjectiveTo investigate whether internet-delivered CBT implemented in a stepped-care model is noninferior to in-person CBT for pediatric obsessive-compulsive disorder. Design, Setting and ParticipantsA randomized clinical noninferiority trial conducted at 2 specialist child and adolescent mental health clinics in Sweden. Participants included 152 individuals aged 8 to 17 years with obsessive-compulsive disorder. Enrollment began in October 2017 and ended in May 2019. Follow-up ended in April 2020. InterventionsParticipants randomized to the stepped-care group (n=74) received internet-delivered CBT for 16 weeks. Nonresponders at the 3-month follow-up were then offered a course of traditional face-to-face treatment. Participants randomized to the control group (n=78) immediately received in-person CBT for 16 weeks. Nonresponders at the 3-month follow-up received additional face-to-face treatment. Main Outcomes and MeasuresThe primary outcome was the masked assessor-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score at the 6-month follow-up. The scale includes 10 items rated from 0(no symptoms) to 4(extreme symptoms), yielding a total score range of 0 to 40, with higher scores indicating greater severity. Assessors were masked to treatment allocation at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up assessments. The predefined noninferiority margin was 4 points on the CY-BOCS. ResultsAmong the 152 randomized participants (mean age, 13.4 years; 94 [62%] females), 151 (99%) completed the trial. At the 3-month follow-up, 34 participants (46%) in the stepped-care group and 23 (30%) in the in-person CBT group were nonresponders. At the 6-month follow-up, the CY-BOCS score was 11.57 points in the stepped-care group vs 10.57 points in the face-to-face treatment group, corresponding to an estimated mean difference of 0.91 points ([1-sided 97.5% CI, -infinity to 3.28]; P for noninferiority=.02). Increased anxiety (30%-36%) and depressive symptoms (20%-28%) were the most frequently reported adverse events in both groups. There were 2 unrelated serious adverse events (1 in each group). Conclusions and RelevanceAmong children and adolescents with obsessive-compulsive disorder, treatment with an internet-delivered CBT program followed by in-person CBT if necessary compared with in-person CBT alone resulted in a noninferior difference in symptoms at the 6-month follow-up. Further research is needed to understand the durability and generalizability of these findings. Trial RegistrationClinicalTrials.gov Identifier: NCT03263546 This noninferiority trial compares the effects of an internet-delivered cognitive behavioral therapy (CBT) program followed by traditional in-person CBT if necessary vs in-person CBT alone on symptoms of obsessive compulsive disorder (OCD) in children and adolescents.
  • Krebs, G., et al. (författare)
  • Concurrent and prospective associations of obsessive-compulsive symptoms with suicidality in young adults: A genetically-informative study
  • 2021
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 281, s. 422-430
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obsessive-compulsive disorder (OCD) has been linked with elevated risk of suicidality. However, most previous studies have been cross-sectional, and little is known about the aetiology of the association between obsessive-compulsive symptoms (OCS) and suicidality in young adults. Methods: Participants were members of the Child and Adolescent Twin Study in Sweden, at ages 18 (n = 9,162) and 24 (n = 3,466). Twins completed self-report measures, including assessment of OCS, suicidal ideation, and suicidal attempts. Logistic regression models tested concurrent and prospective associations of total OCS and OCS dimensions with suicidality, with and without adjustment for depression and anxiety symptoms. Genetic models tested the extent to which the main phenotypic associations were accounted for by genetic and environmental influences. Results: Total OCS were significantly associated with concurrent reports of suicidality at age 18 and 24, even when controlling for depressive and anxiety symptoms. Taboo obsessions (e.g., sexual and aggressive thoughts) were more robustly associated with suicidality than other OCS dimensions, and prospectively predicted suicidality symptoms over time, even when controlling for baseline suicide attempts. Genetic factors accounted for most of the concurrent and longitudinal covariance between OCS and suicidality, with substantial non-shared environmental influences. Limitations: We relied on self-report measures and did not include diagnostic assessment of OCD. Conclusions: OCS, particularly taboo obsessions, are associated with significantly elevated risk of suicidality in late adolescence and early adulthood. This relationship is explained by a combination of common genetic liability and non-shared environmental effects, suggesting that effective OCS treatment might reduce suicidality risk in this group.
  • Aspvall, K., et al. (författare)
  • Implementation of internet-delivered cognitive behaviour therapy for pediatric obsessive-compulsive disorder: Lessons from clinics in Sweden, United Kingdom and Australia
  • 2020
  • Ingår i: Internet Interventions. - 2214-7829. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Obsessive-compulsive disorder (OCD) can be successfully treated with cognitive behaviour therapy (CBT). However, as few patients have access to CBT, there is a strong push to develop and evaluate scalable and cost-effective internet-delivered interventions. BIP OCD is a therapist-guided online CBT intervention for pediatric OCD that has shown promise in trials conducted at a single site in Stockholm, Sweden. In this study, we evaluated if BIP OCD is an acceptable, feasible, and effective treatment in other countries and clinical contexts. Thirty-one patients were recruited at three different sites; a specialist OCD clinic in Gothenburg (Sweden), a specialist OCD clinic in London (United Kingdom), and a university-based clinic in Brisbane (Australia). Acceptability and feasibility measures included treatment adherence and feedback from therapists. Clinician assessments were conducted at baseline, post-treatment, and 3-month follow-up. The average module completion for the participants was 8.1/12 (SD = 3.2) and the majority of patients completed the BIP OCD treatment (100% in Gothenburg, and 55.6% in both London and Brisbane). Pooling data from the three sites, the within-group effect sizes from baseline to post-treatment on the Children's Yale-Brown Obsessive-Compulsive Scale were in the expected range (bootstrapped Cohen's d = 1.78; 95% CI 1.18–2.39), with an additional symptom reduction to the 3-month follow-up (bootstrapped Cohen's d = 0.27; 95% CI 0.02–0.51). Participating therapists identified both advantages and difficulties supporting patients in this digital format. The results of this study suggest that the treatment effects obtained in the original BIP OCD trials can be generalized to other clinical contexts nationally and internationally. Lessons learned provide important information for successful implementation of BIP OCD in regular healthcare contexts. © 2020 The Authors
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