Pub Date : 2024-10-30DOI: 10.1001/jamapsychiatry.2024.3241
Tarek K Rajji, Christopher R Bowie, Nathan Herrmann, Bruce G Pollock, Krista L Lanctôt, Sanjeev Kumar, Alastair J Flint, Linda Mah, Corinne E Fischer, Meryl A Butters, Marom Bikson, James L Kennedy, Daniel M Blumberger, Zafiris J Daskalakis, Damien Gallagher, Mark J Rapoport, Nicolaas P L G Paul Verhoeff, Angela C Golas, Ariel Graff-Guerrero, Erica Vieira, Aristotle N Voineskos, Heather Brooks, Ashley Melichercik, Kevin E Thorpe, Benoit H Mulsant
Importance: Older adults with major depressive disorder (MDD) or mild cognitive impairment (MCI) are at high risk for cognitive decline.
Objective: To assess the efficacy of cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) targeting the prefrontal cortex in slowing cognitive decline, acutely improving cognition, and reducing progression to MCI or dementia in older adults with remitted MDD (rMDD), MCI, or both.
Design, setting, and participants: This randomized clinical trial was conducted at 5 academic hospitals in Toronto, Ontario, Canada. Participants were older adults who had rMDD (with or without MCI, age ≥65 y) or MCI without rMDD (age ≥60 y). Assessments were made at baseline, month 2, and yearly from baseline for 3 to 7 years.
Interventions: CR plus tDCS (hereafter, active) or sham plus sham 5 days a week for 8 weeks followed by twice-a-year 5-day boosters and daily at-home CR or sham CR.
Main outcomes and measures: The primary outcome was change in global composite cognitive score. Secondary outcomes included changes in 6 cognitive domains, moderating effect of the diagnosis, moderating effect of APOE ε4 status, change in composite score at month 2, and progression to MCI or dementia over time.
Results: Of 486 older adults who provided consent, 375 (with rMDD, MCI, or both) received at least 1 intervention session (mean [SD] age, 72.2 [6.4] years; 232 women [62%] and 143 men [38%]). Over a median follow-up of 48.3 months (range, 2.1-85.9), CR and tDCS slowed cognitive decline in older adults with rMDD or MCI (adjusted z score difference [active - sham] at month 60, 0.21; 95% CI, 0.07 to 0.35; likelihood ratio test [LRT] P = .006). In the preplanned primary analysis, CR and tDCS did not improve cognition acutely (adjusted z score difference [active - sham] at month 2, 0.06, 95% CI, -0.006 to 0.12). Similarly, the effect of CR and tDCS on delaying progression from normal cognition to MCI or MCI to dementia was weak and not significant (hazard ratio, 0.66; 95% CI, 0.40 to 1.08; P = .10). Preplanned analyses showed treatment effects for executive function (LRT P = .04) and verbal memory (LRT P = .02) and interactions with diagnosis (P = .01) and APOE ε4 (P < .001) demonstrating a larger effect among those with rMDD and in noncarriers of APOE ε4.
Conclusions and relevance: The study showed that CR and tDCS, both targeting the prefrontal cortex, is efficacious in slowing cognitive decline in older adults at risk of cognitive decline, particularly those with rMDD (with or without MCI) and in those at low genetic risk for Alzheimer disease.
{"title":"Slowing Cognitive Decline in Major Depressive Disorder and Mild Cognitive Impairment: A Randomized Clinical Trial.","authors":"Tarek K Rajji, Christopher R Bowie, Nathan Herrmann, Bruce G Pollock, Krista L Lanctôt, Sanjeev Kumar, Alastair J Flint, Linda Mah, Corinne E Fischer, Meryl A Butters, Marom Bikson, James L Kennedy, Daniel M Blumberger, Zafiris J Daskalakis, Damien Gallagher, Mark J Rapoport, Nicolaas P L G Paul Verhoeff, Angela C Golas, Ariel Graff-Guerrero, Erica Vieira, Aristotle N Voineskos, Heather Brooks, Ashley Melichercik, Kevin E Thorpe, Benoit H Mulsant","doi":"10.1001/jamapsychiatry.2024.3241","DOIUrl":"10.1001/jamapsychiatry.2024.3241","url":null,"abstract":"<p><strong>Importance: </strong>Older adults with major depressive disorder (MDD) or mild cognitive impairment (MCI) are at high risk for cognitive decline.</p><p><strong>Objective: </strong>To assess the efficacy of cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) targeting the prefrontal cortex in slowing cognitive decline, acutely improving cognition, and reducing progression to MCI or dementia in older adults with remitted MDD (rMDD), MCI, or both.</p><p><strong>Design, setting, and participants: </strong>This randomized clinical trial was conducted at 5 academic hospitals in Toronto, Ontario, Canada. Participants were older adults who had rMDD (with or without MCI, age ≥65 y) or MCI without rMDD (age ≥60 y). Assessments were made at baseline, month 2, and yearly from baseline for 3 to 7 years.</p><p><strong>Interventions: </strong>CR plus tDCS (hereafter, active) or sham plus sham 5 days a week for 8 weeks followed by twice-a-year 5-day boosters and daily at-home CR or sham CR.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was change in global composite cognitive score. Secondary outcomes included changes in 6 cognitive domains, moderating effect of the diagnosis, moderating effect of APOE ε4 status, change in composite score at month 2, and progression to MCI or dementia over time.</p><p><strong>Results: </strong>Of 486 older adults who provided consent, 375 (with rMDD, MCI, or both) received at least 1 intervention session (mean [SD] age, 72.2 [6.4] years; 232 women [62%] and 143 men [38%]). Over a median follow-up of 48.3 months (range, 2.1-85.9), CR and tDCS slowed cognitive decline in older adults with rMDD or MCI (adjusted z score difference [active - sham] at month 60, 0.21; 95% CI, 0.07 to 0.35; likelihood ratio test [LRT] P = .006). In the preplanned primary analysis, CR and tDCS did not improve cognition acutely (adjusted z score difference [active - sham] at month 2, 0.06, 95% CI, -0.006 to 0.12). Similarly, the effect of CR and tDCS on delaying progression from normal cognition to MCI or MCI to dementia was weak and not significant (hazard ratio, 0.66; 95% CI, 0.40 to 1.08; P = .10). Preplanned analyses showed treatment effects for executive function (LRT P = .04) and verbal memory (LRT P = .02) and interactions with diagnosis (P = .01) and APOE ε4 (P < .001) demonstrating a larger effect among those with rMDD and in noncarriers of APOE ε4.</p><p><strong>Conclusions and relevance: </strong>The study showed that CR and tDCS, both targeting the prefrontal cortex, is efficacious in slowing cognitive decline in older adults at risk of cognitive decline, particularly those with rMDD (with or without MCI) and in those at low genetic risk for Alzheimer disease.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02386670.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1001/jamapsychiatry.2024.3426
Allison M Lake, Yu Zhou, Bo Wang, Ky'Era V Actkins, Yingzhe Zhang, John P Shelley, Anindita Rajamani, Michael Steigman, Chris J Kennedy, Jordan W Smoller, Karmel W Choi, Nikhil K Khankari, Lea K Davis
<p><strong>Importance: </strong>Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts.</p><p><strong>Objective: </strong>To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting.</p><p><strong>Design, setting, and participants: </strong>This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024.</p><p><strong>Exposures: </strong>Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder.</p><p><strong>Main outcomes and measures: </strong>Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables.</p><p><strong>Results: </strong>Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interac
{"title":"Sexual Trauma, Polygenic Scores, and Mental Health Diagnoses and Outcomes.","authors":"Allison M Lake, Yu Zhou, Bo Wang, Ky'Era V Actkins, Yingzhe Zhang, John P Shelley, Anindita Rajamani, Michael Steigman, Chris J Kennedy, Jordan W Smoller, Karmel W Choi, Nikhil K Khankari, Lea K Davis","doi":"10.1001/jamapsychiatry.2024.3426","DOIUrl":"10.1001/jamapsychiatry.2024.3426","url":null,"abstract":"<p><strong>Importance: </strong>Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts.</p><p><strong>Objective: </strong>To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting.</p><p><strong>Design, setting, and participants: </strong>This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024.</p><p><strong>Exposures: </strong>Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder.</p><p><strong>Main outcomes and measures: </strong>Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables.</p><p><strong>Results: </strong>Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interac","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1001/jamapsychiatry.2024.3231
Justin D Russell,Sara A Heyn,Matthew Peverill,Samantha DiMaio,Ryan J Herringa
ImportanceWhile adverse childhood experiences (ACEs) are known to impart significant risk for negative mental health and cognitive outcomes in youth, translation of ACE scores into clinical intervention is limited by poor specificity in predicting negative outcomes. This work expands on the ACE framework using a data-driven approach to identify 8 different forms of traumatic and adverse childhood experiences (TRACEs) and reveal their differential associations with psychiatric risk and cognition across development.ObjectiveBuilding upon the traditional ACEs model, this study aimed to characterize unique components of commonly co-occurring TRACEs and to examine moderation of longitudinal change in mental health and cognitive development during adolescence.Design, Setting, and ParticipantsThis work draws from youth and their caregivers who completed up to 4 annual behavioral assessments from 2016 to 2021 as part of the ongoing Adolescent Brain Cognitive Development (ABCD) study. Data collection was performed at 21 regionally-distributed sites across the United States. Analyses for this work were conducted January 2023 through November 2023.ExposuresYouth participants in the ABCD study's exposure to 268 different TRACEs, which were distilled into adversity components using nonlinear principal components analysis.Main Outcomes and MeasuresMixed-effects and latent change score models considered TRACEs components as moderators of longitudinal change in internalizing and externalizing mental health problems, as well as longitudinal change in cognitive ability.ResultsData were distilled from 11 876 youth participants, who were grouped into dyads with a caregiver. ABCD study youth participants were 9 to 10 years old at baseline assessment (year 0) and 12 to 13 years old at ABCD year 3. A total of 5679 participants (47.8%) were female. Analyses revealed that TRACEs organized into 8 thematic adversity components (e.g., family conflict, interpersonal violence). At baseline assessment (year 0), exposure to nearly every adversity component was associated with poorer mental health and diminished cognitive ability. Yet across time, it was observed that different forms of adversity were variably linked to both increases and decreases in internalizing and externalizing problems. For example, while peer aggression (t = 5.31) and family conflict (t = 5.67) were associated with increases in both internalizing and externalizing problems over early adolescence, community threat (t = 2.82) and poverty (t = 2.07) were linked to decreased problems, potentially representing adaptive suppression of symptoms. Finally, adversity types related to resource deprivation (eg, poverty, caregiver maladjustment) were associated with declines in cognitive ability over early adolescence.Conclusions and RelevanceIn this cohort study, distinct forms of TRACEs differentially moderated developmental changes in psychiatric risk and cognitive ability in different ways, offering the possibilit
{"title":"Traumatic and Adverse Childhood Experiences and Developmental Differences in Psychiatric Risk.","authors":"Justin D Russell,Sara A Heyn,Matthew Peverill,Samantha DiMaio,Ryan J Herringa","doi":"10.1001/jamapsychiatry.2024.3231","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3231","url":null,"abstract":"ImportanceWhile adverse childhood experiences (ACEs) are known to impart significant risk for negative mental health and cognitive outcomes in youth, translation of ACE scores into clinical intervention is limited by poor specificity in predicting negative outcomes. This work expands on the ACE framework using a data-driven approach to identify 8 different forms of traumatic and adverse childhood experiences (TRACEs) and reveal their differential associations with psychiatric risk and cognition across development.ObjectiveBuilding upon the traditional ACEs model, this study aimed to characterize unique components of commonly co-occurring TRACEs and to examine moderation of longitudinal change in mental health and cognitive development during adolescence.Design, Setting, and ParticipantsThis work draws from youth and their caregivers who completed up to 4 annual behavioral assessments from 2016 to 2021 as part of the ongoing Adolescent Brain Cognitive Development (ABCD) study. Data collection was performed at 21 regionally-distributed sites across the United States. Analyses for this work were conducted January 2023 through November 2023.ExposuresYouth participants in the ABCD study's exposure to 268 different TRACEs, which were distilled into adversity components using nonlinear principal components analysis.Main Outcomes and MeasuresMixed-effects and latent change score models considered TRACEs components as moderators of longitudinal change in internalizing and externalizing mental health problems, as well as longitudinal change in cognitive ability.ResultsData were distilled from 11 876 youth participants, who were grouped into dyads with a caregiver. ABCD study youth participants were 9 to 10 years old at baseline assessment (year 0) and 12 to 13 years old at ABCD year 3. A total of 5679 participants (47.8%) were female. Analyses revealed that TRACEs organized into 8 thematic adversity components (e.g., family conflict, interpersonal violence). At baseline assessment (year 0), exposure to nearly every adversity component was associated with poorer mental health and diminished cognitive ability. Yet across time, it was observed that different forms of adversity were variably linked to both increases and decreases in internalizing and externalizing problems. For example, while peer aggression (t = 5.31) and family conflict (t = 5.67) were associated with increases in both internalizing and externalizing problems over early adolescence, community threat (t = 2.82) and poverty (t = 2.07) were linked to decreased problems, potentially representing adaptive suppression of symptoms. Finally, adversity types related to resource deprivation (eg, poverty, caregiver maladjustment) were associated with declines in cognitive ability over early adolescence.Conclusions and RelevanceIn this cohort study, distinct forms of TRACEs differentially moderated developmental changes in psychiatric risk and cognitive ability in different ways, offering the possibilit","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"34 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1001/jamapsychiatry.2024.3228
Carlos Blanco,Craig B H Surman
{"title":"Diagnosing and Treating ADHD in Adults: Balancing Individual Benefits and Population Risks.","authors":"Carlos Blanco,Craig B H Surman","doi":"10.1001/jamapsychiatry.2024.3228","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3228","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"125 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1001/jamapsychiatry.2024.3076
Erin L Winstanley,Angela Gray,Douglas Thornton
{"title":"Addressing the Escalating Problems That Patients Encounter When Filling Buprenorphine Prescriptions.","authors":"Erin L Winstanley,Angela Gray,Douglas Thornton","doi":"10.1001/jamapsychiatry.2024.3076","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3076","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"74 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1001/jamapsychiatry.2024.3194
Charlotte M Pretzsch,Martina Arenella,Jason P Lerch,Michael V Lombardo,Christian Beckmann,Tim Schaefer,Johanna Leyhausen,Caroline Gurr,Anke Bletsch,Lisa M Berg,Hanna Seelemeyer,Dorothea L Floris,Bethany Oakley,Eva Loth,Thomas Bourgeron,Tony Charman,Jan Buitelaar,Grainne McAlonan,Declan Murphy,Christine Ecker,
ImportanceIn the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear.ObjectivesTo examine if, in autism, brain regions develop differently in relation to each other and how these differences are associated with molecular/genomic mechanisms and symptomatology.Design, Setting, and ParticipantsThis study was an analysis of one the largest deep-phenotyped, case-control, longitudinal (2 assessments separated by approximately 12-24 months) structural magnetic resonance imaging and cognitive-behavioral autism datasets (EU-AIMS Longitudinal European Autism Project [LEAP]; study dates, February 2014-November 2017) and an out-of-sample validation in the Brain Development Imaging Study (BrainMapASD) independent cohort. Analyses were performed during the 2022 to 2023 period. This multicenter study included autistic and neurotypical children, adolescents, and adults. Autistic participants were included if they had an existing autism diagnosis (DSM-IV/International Statistical Classification of Diseases and Related Health Problems, Tenth Revision or DSM-5 criteria). Autistic participants with co-occurring psychiatric conditions (except psychosis/bipolar disorder) and those taking regular medications were included.ExposuresNeuroanatomy of neurotypical and autistic participants.Main Outcomes and MeasuresIntraindividual changes in surface area and cortical thickness over time, analyzed via surface-based morphometrics.ResultsA total of 386 individuals in the LEAP cohort (6-31 years at first visit; 214 autistic individuals, mean [SD] age, 17.3 [5.4] years; 154 male [72.0%] and 172 neurotypical individuals, mean [SD] age, 16.35 [5.7] years; 108 male [62.8%]) and 146 individuals in the BrainMapASD cohort (11-18 years at first visit; 49 autistic individuals, mean [SD] age, 14.31 [2.4] years; 42 male [85.7%] and 97 neurotypical individuals, mean [SD] age, 14.10 [2.5] years; 58 male [59.8%]). Maturational between-group differences in cortical thickness and surface area were established that were mostly driven by sensorimotor regions (eg, across features, absolute loadings for early visual cortex ranged from 0.07 to 0.11, whereas absolute loadings for dorsolateral prefrontal cortex ranged from 0.005 to 0.06). Neurodevelopmental differences were transcriptomically enriched for genes expressed in several cell types and during various neurodevelopmental stages, and autism candidate genes (eg, downregulated genes in autism, including those regulating synaptic transmission; enrichment odds ratio =3.7; P =2.6 × -10). A more neurotypical, less autismlike maturational profile was associated with fewer social difficulties and more typical sensory processing (false discovery rate P <.05; Pearson r ≥0.17). Results were replicated in the independently collected BrainMapASD cohort.Conclu
{"title":"Patterns of Brain Maturation in Autism and Their Molecular Associations.","authors":"Charlotte M Pretzsch,Martina Arenella,Jason P Lerch,Michael V Lombardo,Christian Beckmann,Tim Schaefer,Johanna Leyhausen,Caroline Gurr,Anke Bletsch,Lisa M Berg,Hanna Seelemeyer,Dorothea L Floris,Bethany Oakley,Eva Loth,Thomas Bourgeron,Tony Charman,Jan Buitelaar,Grainne McAlonan,Declan Murphy,Christine Ecker,","doi":"10.1001/jamapsychiatry.2024.3194","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3194","url":null,"abstract":"ImportanceIn the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear.ObjectivesTo examine if, in autism, brain regions develop differently in relation to each other and how these differences are associated with molecular/genomic mechanisms and symptomatology.Design, Setting, and ParticipantsThis study was an analysis of one the largest deep-phenotyped, case-control, longitudinal (2 assessments separated by approximately 12-24 months) structural magnetic resonance imaging and cognitive-behavioral autism datasets (EU-AIMS Longitudinal European Autism Project [LEAP]; study dates, February 2014-November 2017) and an out-of-sample validation in the Brain Development Imaging Study (BrainMapASD) independent cohort. Analyses were performed during the 2022 to 2023 period. This multicenter study included autistic and neurotypical children, adolescents, and adults. Autistic participants were included if they had an existing autism diagnosis (DSM-IV/International Statistical Classification of Diseases and Related Health Problems, Tenth Revision or DSM-5 criteria). Autistic participants with co-occurring psychiatric conditions (except psychosis/bipolar disorder) and those taking regular medications were included.ExposuresNeuroanatomy of neurotypical and autistic participants.Main Outcomes and MeasuresIntraindividual changes in surface area and cortical thickness over time, analyzed via surface-based morphometrics.ResultsA total of 386 individuals in the LEAP cohort (6-31 years at first visit; 214 autistic individuals, mean [SD] age, 17.3 [5.4] years; 154 male [72.0%] and 172 neurotypical individuals, mean [SD] age, 16.35 [5.7] years; 108 male [62.8%]) and 146 individuals in the BrainMapASD cohort (11-18 years at first visit; 49 autistic individuals, mean [SD] age, 14.31 [2.4] years; 42 male [85.7%] and 97 neurotypical individuals, mean [SD] age, 14.10 [2.5] years; 58 male [59.8%]). Maturational between-group differences in cortical thickness and surface area were established that were mostly driven by sensorimotor regions (eg, across features, absolute loadings for early visual cortex ranged from 0.07 to 0.11, whereas absolute loadings for dorsolateral prefrontal cortex ranged from 0.005 to 0.06). Neurodevelopmental differences were transcriptomically enriched for genes expressed in several cell types and during various neurodevelopmental stages, and autism candidate genes (eg, downregulated genes in autism, including those regulating synaptic transmission; enrichment odds ratio =3.7; P =2.6 × -10). A more neurotypical, less autismlike maturational profile was associated with fewer social difficulties and more typical sensory processing (false discovery rate P <.05; Pearson r ≥0.17). Results were replicated in the independently collected BrainMapASD cohort.Conclu","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"68 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1001/jamapsychiatry.2024.3049
Jessica Girault
{"title":"Development of Sensory Regions vs the Rest of the Cortex in Autism.","authors":"Jessica Girault","doi":"10.1001/jamapsychiatry.2024.3049","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3049","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"1 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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