Pub Date : 2024-08-01DOI: 10.1016/j.jaac.2024.04.007
{"title":"Happiness Falls","authors":"","doi":"10.1016/j.jaac.2024.04.007","DOIUrl":"10.1016/j.jaac.2024.04.007","url":null,"abstract":"","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141027799","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 : 2024-08-01DOI: 10.1016/j.jaac.2023.09.550
Objective
Accumulative evidence indicates a critical role of mitochondrial function in autism spectrum disorders (ASD), implying that ASD risk may be linked to mitochondrial dysfunction due to DNA (mtDNA) variations. Although a few studies have explored the association between mtDNA variations and ASD, the role of mtDNA in ASD is still unclear. Here, we aimed to investigate whether mitochondrial DNA haplogroups are associated with the risk of ASD.
Method
Two European cohorts and an Ashkenazi Jewish (AJ) cohort were analyzed, including 2,062 ASD patients in comparison with 4,632 healthy controls. DNA samples were genotyped using Illumina HumanHap550/610 and Illumina 1M arrays, inclusive of mitochondrial markers. Mitochondrial DNA (mtDNA) haplogroups were identified from genotyping data using HaploGrep2. A mitochondrial genome imputation pipeline was established to detect mtDNA variants. We conducted a case-control study to investigate potential associations of mtDNA haplogroups and variants with the susceptibility to ASD.
Results
We observed that the ancient adaptive mtDNA haplogroup K was significantly associated with decreased risk of ASD by the investigation of 2 European cohorts including a total of 2,006 cases and 4,435 controls (odds ratio = 0.64, P=1.79 × 10–5), and we replicated this association in an Ashkenazi Jewish (AJ) cohort including 56 cases and 197 controls (odds ratio = 0.35, P = 9.46 × 10–3). Moreover, we demonstrate that the mtDNA variants rs28358571, rs28358584, and rs28358280 are significantly associated with ASD risk. Further expression quantitative trait loci (eQTLs) analysis indicated that the rs28358584 and rs28358280 genotypes are associated with expression levels of nearby genes in brain tissues, suggesting those mtDNA variants may confer risk for ASD via regulation of expression levels of genes encoded by the mitochondrial genome.
Conclusion
This study helps to shed light on the contribution of mitochondria in ASD and provides new insights into the genetic mechanism underlying ASD, suggesting the potential involvement of mtDNA-encoded proteins in the development of ASD.
Plain language summary
Increasing evidence indicates that mitochondrial dysfunction may be linked to autism spectrum disorder (ASD). This study investigated potential associations of mitochondrial DNA (mtDNA) variants in 2 European and Ashkenazi Jewish cohorts including 2,062 individuals with ASD and 4,632 healthy controls. Researchers found that the ancient mtDNA haplogroup K was linked to a reduced risk of ASD in both European and Ashkenazi Jewish populations. Additionally, specific mtDNA variants were associated with ASD risk and were shown to influence the expression of nearby genes in the brain. These findings highlight the potential involvement of mtDNA in ASD development, offering new insights
{"title":"Mitochondrial DNA Haplogroup K Is Protective Against Autism Spectrum Disorder Risk in Populations of European Ancestry","authors":"","doi":"10.1016/j.jaac.2023.09.550","DOIUrl":"10.1016/j.jaac.2023.09.550","url":null,"abstract":"<div><h3>Objective</h3><p>Accumulative evidence indicates a critical role of mitochondrial function in autism spectrum disorders (ASD), implying that ASD risk may be linked to mitochondrial dysfunction due to DNA (mtDNA) variations. Although a few studies have explored the association between mtDNA variations and ASD, the role of mtDNA in ASD is still unclear. Here, we aimed to investigate whether mitochondrial DNA haplogroups are associated with the risk of ASD.</p></div><div><h3>Method</h3><p>Two European cohorts and an Ashkenazi Jewish (AJ) cohort were analyzed, including 2,062 ASD patients in comparison with 4,632 healthy controls. DNA samples were genotyped using Illumina HumanHap550/610 and Illumina 1M arrays, inclusive of mitochondrial markers. Mitochondrial DNA (mtDNA) haplogroups were identified from genotyping data using HaploGrep2. A mitochondrial genome imputation pipeline was established to detect mtDNA variants. We conducted a case-control study to investigate potential associations of mtDNA haplogroups and variants with the susceptibility to ASD.</p></div><div><h3>Results</h3><p>We observed that the ancient adaptive mtDNA haplogroup K was significantly associated with decreased risk of ASD by the investigation of 2 European cohorts including a total of 2,006 cases and 4,435 controls (odds ratio = 0.64, <em>P=</em>1.79 × 10<sup>–5</sup>), and we replicated this association in an Ashkenazi Jewish (AJ) cohort including 56 cases and 197 controls (odds ratio = 0.35, <em>P =</em> 9.46 × 10<sup>–3</sup>). Moreover, we demonstrate that the mtDNA variants rs28358571, rs28358584, and rs28358280 are significantly associated with ASD risk. Further expression quantitative trait loci (eQTLs) analysis indicated that the rs28358584 and rs28358280 genotypes are associated with expression levels of nearby genes in brain tissues, suggesting those mtDNA variants may confer risk for ASD via regulation of expression levels of genes encoded by the mitochondrial genome.</p></div><div><h3>Conclusion</h3><p>This study helps to shed light on the contribution of mitochondria in ASD and provides new insights into the genetic mechanism underlying ASD, suggesting the potential involvement of mtDNA-encoded proteins in the development of ASD.</p></div><div><h3>Plain language summary</h3><p>Increasing evidence indicates that mitochondrial dysfunction may be linked to autism spectrum disorder (ASD). This study investigated potential associations of mitochondrial DNA (mtDNA) variants in 2 European and Ashkenazi Jewish cohorts including 2,062 individuals with ASD and 4,632 healthy controls. Researchers found that the ancient mtDNA haplogroup K was linked to a reduced risk of ASD in both European and Ashkenazi Jewish populations. Additionally, specific mtDNA variants were associated with ASD risk and were shown to influence the expression of nearby genes in the brain. These findings highlight the potential involvement of mtDNA in ASD development, offering new insights ","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138550949","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 : 2024-08-01DOI: 10.1016/S0890-8567(24)00271-5
{"title":"Council Page","authors":"","doi":"10.1016/S0890-8567(24)00271-5","DOIUrl":"10.1016/S0890-8567(24)00271-5","url":null,"abstract":"","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949564","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 : 2024-08-01DOI: 10.1016/j.jaac.2023.08.014
{"title":"Youth With Sexual or Gender-Diverse Identities and Military Connection: Recommendations to Optimize Clinical Care","authors":"","doi":"10.1016/j.jaac.2023.08.014","DOIUrl":"10.1016/j.jaac.2023.08.014","url":null,"abstract":"","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41148238","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 : 2024-08-01DOI: 10.1016/j.jaac.2024.04.009
{"title":"Editorial: Can Improving Youth Mental Health Reduce Mortality?","authors":"","doi":"10.1016/j.jaac.2024.04.009","DOIUrl":"10.1016/j.jaac.2024.04.009","url":null,"abstract":"","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890957","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 : 2024-08-01DOI: 10.1016/j.jaac.2024.04.008
{"title":"The Myth of Normal: Trauma, Illness & Healing in a Toxic Culture","authors":"","doi":"10.1016/j.jaac.2024.04.008","DOIUrl":"10.1016/j.jaac.2024.04.008","url":null,"abstract":"","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141037368","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 : 2024-08-01DOI: 10.1016/j.jaac.2023.12.002
{"title":"Editorial: Mitochondrial Gene Variations Increase Autism Risk: Uncovering the Complex Polygenetic Landscape of Autism","authors":"","doi":"10.1016/j.jaac.2023.12.002","DOIUrl":"10.1016/j.jaac.2023.12.002","url":null,"abstract":"","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138551031","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 : 2024-07-31DOI: 10.1016/j.jaac.2024.07.914
Randy P Auerbach
Alarmingly, suicide is now a leading cause of death for preadolescent youth (ie, less than 13 years of age), and among community samples, 2.56% report lifetime suicide attempts with 15.08% experiencing suicidal ideation.1 Predictable but preventable factors have conspired to propel us toward this public health crisis. Chief among them is that approximately 45% of individuals in the United States reside in communities with shortages of mental health professionals,2 a problem that is disproportionately affecting youth of color. The reduced access to psychiatric care means that treatment for many preadolescent youth, particularly during non-acute periods when many interventions are most effective, is delayed given limited clinician availability. Furthermore, the increased acuity of the modal case may be contributing to clinician burnout, further diminishing an already beleaguered workforce. Moreover, societal cracks present prior to the COVID-19 pandemic were further exacerbated, including increased loneliness and isolation3 as well as educational inequities,4 which have led to more pronounced social disconnectedness and greater stress exposure (eg, academic challenges)-factors directly implicated in suicidal thoughts and behaviors (STB).5 Although substantial efforts are underway to improve the short-term prediction of adolescent and adult STB, limited research has focused on clarifying which preadolescent youth are at risk and when that risk is greatest.
{"title":"Editorial: Why Are Children Hurting Themselves and What Can We Do?","authors":"Randy P Auerbach","doi":"10.1016/j.jaac.2024.07.914","DOIUrl":"10.1016/j.jaac.2024.07.914","url":null,"abstract":"<p><p>Alarmingly, suicide is now a leading cause of death for preadolescent youth (ie, less than 13 years of age), and among community samples, 2.56% report lifetime suicide attempts with 15.08% experiencing suicidal ideation.<sup>1</sup> Predictable but preventable factors have conspired to propel us toward this public health crisis. Chief among them is that approximately 45% of individuals in the United States reside in communities with shortages of mental health professionals,<sup>2</sup> a problem that is disproportionately affecting youth of color. The reduced access to psychiatric care means that treatment for many preadolescent youth, particularly during non-acute periods when many interventions are most effective, is delayed given limited clinician availability. Furthermore, the increased acuity of the modal case may be contributing to clinician burnout, further diminishing an already beleaguered workforce. Moreover, societal cracks present prior to the COVID-19 pandemic were further exacerbated, including increased loneliness and isolation<sup>3</sup> as well as educational inequities,<sup>4</sup> which have led to more pronounced social disconnectedness and greater stress exposure (eg, academic challenges)-factors directly implicated in suicidal thoughts and behaviors (STB).<sup>5</sup> Although substantial efforts are underway to improve the short-term prediction of adolescent and adult STB, limited research has focused on clarifying which preadolescent youth are at risk and when that risk is greatest.</p>","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878949","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 : 2024-07-31DOI: 10.1016/j.jaac.2024.07.913
Julia N Stimpfl, Katherine C Soe
Atypical antipsychotics are often effective for managing behavioral disturbances in children with neurodevelopmental disabilities; however, limited evidence-based pharmacologic therapies exist for those dependent upon intravenous and transdermal routes. Transdermal asenapine is US Food and Drug Administration (FDA) approved for adult schizophrenia, but lacks data regarding pediatric use and tolerability. To our knowledge, there are no reports of transdermal asenapine use in children.1,2 Sublingual asenapine is FDA approved for pediatric bipolar mania monotherapy (ages 10-17 years), but was found to lack efficacy for schizophrenia in adolescents.1,3-5 Reportedly, its pediatric tolerability profile resembles those of other second-generation antipsychotics, with pharmacokinetic and safety data comparable to those in adults.3,6,7 We present the case of a 5-year-old child for whom transdermal asenapine effectively and safely managed agitation and improved tolerance of medical therapies and quality of life. Our case suggests that this may be an effective, well-tolerated pharmacologic option for agitation management in a subset of children. Guardian informed consent was obtained prior to publication.
非典型抗精神病药物通常能有效控制神经发育障碍儿童的行为障碍;然而,对于那些依赖静脉注射和透皮途径的儿童来说,循证药物疗法却十分有限。美国食品和药物管理局(FDA)批准透皮阿塞那平用于治疗成人精神分裂症,但缺乏有关儿童使用和耐受性的数据。1,2阿塞那平舌下含服已获 FDA 批准用于小儿双相躁狂症的单药治疗(10-17 岁),但对青少年精神分裂症缺乏疗效。据报道,其儿科耐受性与其他第二代抗精神病药物相似,药代动力学和安全性数据与成人相当。3,6,7 我们介绍了一例 5 岁儿童的病例,经皮阿塞那平可有效、安全地控制躁动,改善对药物治疗的耐受性和生活质量。我们的病例表明,这可能是一种有效、耐受性良好的药物治疗方法,适用于部分儿童的躁动控制。本文发表前已获得监护人的知情同意。
{"title":"Transdermal Asenapine for Agitation and Irritability in a Child With Complete Intravenous Dependence.","authors":"Julia N Stimpfl, Katherine C Soe","doi":"10.1016/j.jaac.2024.07.913","DOIUrl":"10.1016/j.jaac.2024.07.913","url":null,"abstract":"<p><p>Atypical antipsychotics are often effective for managing behavioral disturbances in children with neurodevelopmental disabilities; however, limited evidence-based pharmacologic therapies exist for those dependent upon intravenous and transdermal routes. Transdermal asenapine is US Food and Drug Administration (FDA) approved for adult schizophrenia, but lacks data regarding pediatric use and tolerability. To our knowledge, there are no reports of transdermal asenapine use in children.<sup>1</sup><sup>,</sup><sup>2</sup> Sublingual asenapine is FDA approved for pediatric bipolar mania monotherapy (ages 10-17 years), but was found to lack efficacy for schizophrenia in adolescents.<sup>1</sup><sup>,</sup><sup>3-5</sup> Reportedly, its pediatric tolerability profile resembles those of other second-generation antipsychotics, with pharmacokinetic and safety data comparable to those in adults.<sup>3</sup><sup>,</sup><sup>6</sup><sup>,</sup><sup>7</sup> We present the case of a 5-year-old child for whom transdermal asenapine effectively and safely managed agitation and improved tolerance of medical therapies and quality of life. Our case suggests that this may be an effective, well-tolerated pharmacologic option for agitation management in a subset of children. Guardian informed consent was obtained prior to publication.</p>","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878948","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 : 2024-07-26DOI: 10.1016/j.jaac.2024.07.911
Andrew S Chun, Alex S Keuroghlian
The COVID-19 pandemic has had a profound impact on educational services, leading the World Bank, UNESCO, and UNICEF to jointly declare the "worst educational crisis on record."1 In the United States, standardized testing revealed large declines in reading and mathematics.1 Disadvantaged students have been disproportionately affected as the achievement gap widened for students from historically marginalized and low-income backgrounds.1 Experts predict a culminative exacerbation of these learning losses in the years ahead.1.
{"title":"The Education Crisis and the Allied Role of School-Based Mental Health Care.","authors":"Andrew S Chun, Alex S Keuroghlian","doi":"10.1016/j.jaac.2024.07.911","DOIUrl":"10.1016/j.jaac.2024.07.911","url":null,"abstract":"<p><p>The COVID-19 pandemic has had a profound impact on educational services, leading the World Bank, UNESCO, and UNICEF to jointly declare the \"worst educational crisis on record.\"<sup>1</sup> In the United States, standardized testing revealed large declines in reading and mathematics.<sup>1</sup> Disadvantaged students have been disproportionately affected as the achievement gap widened for students from historically marginalized and low-income backgrounds.<sup>1</sup> Experts predict a culminative exacerbation of these learning losses in the years ahead.<sup>1</sup>.</p>","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788473","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}