Molecular Autism最新文献

{"title":"Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment.","authors":"Hangnyoung Choi, Jae Han Kim, Hee Sang Yang, Jong Yeob Kim, Samuele Cortese, Lee Smith, Ai Koyanagi, Elena Dragioti, Joaquim Radua, Paolo Fusar-Poli, Jae Il Shin, Keun-Ah Cheon, Marco Solmi","doi":"10.1186/s13229-024-00585-6","DOIUrl":"10.1186/s13229-024-00585-6","url":null,"abstract":"<p><strong>Background: </strong>Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions.</p><p><strong>Methods: </strong>We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention.</p><p><strong>Results: </strong>Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each.</p><p><strong>Limitations: </strong>First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants.</p><p><strong>Conclusions: </strong>Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"7"},"PeriodicalIF":6.3,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542774","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}

{"title":"Clinical impact and in vitro characterization of ADNP variants in pediatric patients.","authors":"Chuanhui Ge, Yuxin Tian, Chunchun Hu, Lianni Mei, Dongyun Li, Ping Dong, Ying Zhang, Huiping Li, Daijing Sun, Wenzhu Peng, Xiu Xu, Yan Jiang, Qiong Xu","doi":"10.1186/s13229-024-00584-7","DOIUrl":"10.1186/s13229-024-00584-7","url":null,"abstract":"<p><strong>Background: </strong>Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability.</p><p><strong>Methods: </strong>We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells.</p><p><strong>Results: </strong>Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells.</p><p><strong>Limitations: </strong>Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants.</p><p><strong>Conclusions: </strong>Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"5"},"PeriodicalIF":6.3,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10804707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521370","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}

{"title":"The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers","authors":"Nisha E. Mathew, Delyse McCaffrey, Adam K. Walker, Kylie-Ann Mallitt, Anne Masi, Margaret J. Morris, Chee Y. Ooi","doi":"10.1186/s13229-023-00575-0","DOIUrl":"https://doi.org/10.1186/s13229-023-00575-0","url":null,"abstract":"Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. We extracted data from case–control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"73 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139481396","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}

{"title":"Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort.","authors":"Ting Mei, Alberto Llera, Natalie J Forde, Daan van Rooij, Dorothea L Floris, Christian F Beckmann, Jan K Buitelaar","doi":"10.1186/s13229-024-00583-8","DOIUrl":"10.1186/s13229-024-00583-8","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group.</p><p><strong>Methods: </strong>We studied 781 autistic and 927 non-autistic individuals (6-30 years, IQ ≥ 50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants' loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group.</p><p><strong>Results: </strong>The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (β = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (β = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085).</p><p><strong>Limitations: </strong>The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample.</p><p><strong>Conclusions: </strong>The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"3"},"PeriodicalIF":6.2,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477366","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}

{"title":"Autistic and non-autistic individuals show the same amygdala activity during emotional face processing.","authors":"Benedikt P Langenbach, Dominik Grotegerd, Peter C R Mulders, Indira Tendolkar, Jasper van Oort, Fleur Duyser, Philip van Eijndhoven, Janna N Vrijsen, Udo Dannlowski, Zarah Kampmann, Katja Koelkebeck","doi":"10.1186/s13229-024-00582-9","DOIUrl":"10.1186/s13229-024-00582-9","url":null,"abstract":"<p><strong>Background: </strong>Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people's feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples.</p><p><strong>Methods: </strong>In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns.</p><p><strong>Results: </strong>We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment.</p><p><strong>Limitations: </strong>Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations.</p><p><strong>Conclusions: </strong>Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"2"},"PeriodicalIF":6.2,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417488","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}

{"title":"The association between social camouflage and mental health among autistic people in Japan and the UK: a cross-cultural study","authors":"Fumiyo Oshima, Toru Takahashi, Masaki Tamura, Siqing Guan, Mikuko Seto, Laura Hull, William Mandy, Kenji Tsuchiya, Eiji Shimizu","doi":"10.1186/s13229-023-00579-w","DOIUrl":"https://doi.org/10.1186/s13229-023-00579-w","url":null,"abstract":"To examine the relationship between social camouflage and mental health in Japanese autistic adults and make an international comparison with a sample from the UK. This study analysed secondary data of participants with a self-reported diagnosis of autism from Japan (N = 210; 123 men and 87 women) and the UK (N = 305; 181 women, 104, men, and 18 nonbinary). The relationships between the quadratic term of the Camouflaging Autistic Traits Questionnaire and mental health scales, including depression and anxiety, were assessed. The UK sample showed linear relationships, whereas the Japanese sample showed significant nonlinear relationships. The quadratic terms of the Camouflaging Autistic Traits Questionnaire slightly explained generalised anxiety (β = .168, p = .007), depression (β = .121, p = .045), and well-being (β = − .127, p = .028). However, they did not explain the association between social anxiety and the Camouflaging Autistic Traits Questionnaire. Participants had self-reported diagnoses, and while the autism-spectrum quotient provides a cut-off value for screening, it does not enable confirming diagnoses. Mean scores of the Japanese version of the Camouflaging Autistic Traits Questionnaire were lower as compared to the original CAT-Q, which implies that the social camouflage strategy types used by autistic people in Japan and the UK could differ. The cross-sectional design limits causal inferences. In the UK, more social camouflage was associated with poorer mental health scores, whereas too little or too much social camouflage was associated with a low mental health score in Japan. The Japanese population is seemingly less aware of and educated on autistic characteristics and considers ‘average’ behaviour a good thing. This could influence Japanese autistic people’s social camouflage use, differing from that of autistic people in the UK. The differences in the relationship between social camouflage and mental health between Japan and the UK could be associated with national-level divergence regarding the culture of autism.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139094571","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}

{"title":"The biosocial correlates and predictors of emotion dysregulation in autistic adults compared to borderline personality disorder and nonclinical controls","authors":"Doha Bemmouna, Amine Lagzouli, Luisa Weiner","doi":"10.1186/s13229-023-00580-3","DOIUrl":"https://doi.org/10.1186/s13229-023-00580-3","url":null,"abstract":"Emotion dysregulation (ED) is a core symptom of borderline personality disorder (BPD), whose aetiology has been attributed to biosocial factors. In autism spectrum condition (ASC), although ED is prevalent and is associated with decreased well-being (e.g. self-harm, suicidality), it has been understudied, especially in adults. It is therefore crucial to further understand ED in autistic adults to improve its treatment. Our study investigates ED, its behavioural correlates (e.g. self-harm, suicidality) and biosocial predictors in autistic adults relative to BPD and nonclinical controls (NC). A total of 724 participants (ASC = 154; BPD = 111; NC = 459) completed 11 self-reported questionnaires assessing ED, ASC and BPD traits, co-occurring disorders, alexithymia, emotional vulnerability and invalidating experiences (e.g. bullying, autistic camouflaging). The occurrence of ED behavioural correlates (i.e. self-harm, history of suicide attempts, and psychiatric hospitalizations) was collected. In addition, between-groups analyses, linear regressions and machine learning (ML) models were used to identify ED predictors in each group. ED and its behavioural correlates were higher in ASC compared to NC, but milder than in BPD. While gender did not predict ED scores, autistic women had increased risk factors to ED, including sexual abuse and camouflaging. Interestingly, BPD traits, emotional vulnerability and alexithymia strongly predicted ED scores across the groups. Using ML models, sensory sensitivity and autistic camouflaging were associated with ED in ASC, and ADHD symptoms with ED in BPD. ASC and BPD diagnoses were self-reported, which did not allow us to check their accuracy. Additionally, we did not explore the transactional and the moderating/mediating relationships between the different variables. Moreover, our research is cross-sectional and cannot draw conclusions regarding the direction and causality of relationships between ED and other clinical dimensions. ED and its behavioural correlates are heightened in BPD compared to ASC and nonclinical controls. In the ASC group, there were no gender differences in ED, despite the heightened exposure of autistic women to ED risk factors. BPD traits, emotional vulnerability, and alexithymia are core to ED regardless of diagnosis. Although less central, sensory sensitivity and autistic camouflaging seem to be specific predictors of ED in autistic adults.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"194 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715656","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}

{"title":"Is the association between mothers’ autistic traits and childhood autistic traits moderated by maternal pre-pregnancy body mass index?","authors":"Novika Purnama Sari, Alexandros Tsompanidis, Rama J. Wahab, Romy Gaillard, Ezra Aydin, Rosemary Holt, Carrie Allison, Simon Baron-Cohen, Marinus H. van IJzendoorn, Pauline W. Jansen","doi":"10.1186/s13229-023-00578-x","DOIUrl":"https://doi.org/10.1186/s13229-023-00578-x","url":null,"abstract":"Previous studies showed that there is a positive association between mothers’ and children’s autistic traits. We also tested if this association is more pronounced in mothers with a higher pre-pregnancy body mass index (BMI). The study was embedded in two cohorts with information available for 4,659 participants from the Generation R and for 179 participants from the Cambridge Ultrasound Siblings and Parents Project (CUSP) cohort. In both cohorts, maternal autistic traits were assessed using the short form of the Autism Spectrum Quotient, and information about maternal height and weight before pregnancy was obtained by questionnaire. Child autistic traits were assessed with the short form of Social Responsiveness Scale in Generation R (M = 13.5 years) and with the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in the CUSP cohort (M = 1.6 years). Higher maternal autistic traits were associated with higher autistic traits in toddlerhood (CUSP cohort; βadjusted = 0.20, p < 0.01), in early childhood (Generation R; βadjusted = 0.19, p < 0.01), and in early adolescence (Generation R; βadjusted = 0.16, p < 0.01). Furthermore, a higher maternal pre-pregnancy BMI was associated with higher child autistic traits, but only in Generation R (βadjusted = 0.03, p < 0.01). There was no significant moderating effect of maternal pre-pregnancy BMI on the association between autistic traits of mothers and children, neither in Generation R nor in CUSP. In addition, child autistic traits scores were significantly higher in mothers who were underweight and in mothers who were overweight compared to mothers with a healthy weight. We confirm the association between maternal and child autistic traits in toddlerhood, early childhood, and early adolescence. Potential interacting neurobiological processes remain to be confirmed.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"184 2 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138556154","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}

{"title":"Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications.","authors":"Aline Lefebvre, Nicolas Traut, Amandine Pedoux, Anna Maruani, Anita Beggiato, Monique Elmaleh, David Germanaud, Anouck Amestoy, Myriam Ly-Le Moal, Christopher Chatham, Lorraine Murtagh, Manuel Bouvard, Marianne Alisson, Marion Leboyer, Thomas Bourgeron, Roberto Toro, Guillaume Dumas, Clara Moreau, Richard Delorme","doi":"10.1186/s13229-023-00576-z","DOIUrl":"10.1186/s13229-023-00576-z","url":null,"abstract":"<p><strong>Background: </strong>Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into 'motor-driven' and 'cognitively driven'. RRBI symptomatology depends on the individual's clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures-involving cortical and subcortical areas.</p><p><strong>Method: </strong>A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n = 152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models.</p><p><strong>Results: </strong>We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the 'motor-driven' RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the 'cognitively driven' RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p < 0.05). FA1 was negatively associated with the left amygdala (uncorrected p < 0.05), and FA2 was positively associated with the left parietal structure (uncorrected p = 0.001).</p><p><strong>Conclusion: </strong>Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen's integrative role in RSBI needs to be strengthened in further studies.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"14 1","pages":"45"},"PeriodicalIF":6.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445402","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}

{"title":"Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study.","authors":"Simon Maier, Kathrin Nickel, Thomas Lange, Georg Oeltzschner, Michael Dacko, Dominique Endres, Kimon Runge, Anke Schumann, Katharina Domschke, Michalis Rousos, Ludger Tebartz van Elst","doi":"10.1186/s13229-023-00577-y","DOIUrl":"10.1186/s13229-023-00577-y","url":null,"abstract":"<p><strong>Introduction: </strong>Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs).</p><p><strong>Materials and methods: </strong>Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated.</p><p><strong>Results: </strong>Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p = 0.028; Cohen's d = 0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p = 0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels.</p><p><strong>Limitations: </strong>A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality.</p><p><strong>Conclusion: </strong>This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"14 1","pages":"44"},"PeriodicalIF":6.2,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398216","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}