Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Pretzsch, Loth, Oakley, Murphy, Ecker); Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (Schäfer, Mann, Bletsch, Yousaf, Freitag, Ecker); Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, University of Trento, and Italian Institute of Technology, Rovereto, Italy (Lombardo, Warrier); Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, U.K. (Lombardo, Baron-Cohen); F. Hoffmann-La Roche, Innovation Center Basel, Basel, Switzerland (Chatham); Methods of Plasticity Research, Department of Psychology, University of Zurich, Zurich (Floris); Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands (Buitelaar, Beckmann); Clinical Child Psychology, Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Tillmann, Charman); Department of Applied Psychology: Health, Development, Enhancement, and Intervention, University of Vienna, Vienna (Tillmann); Centre for Brain and Cognitive Development, University of London (Jones); Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands (Ambrosino, Durston); Institut Pasteur, Human Genetics and Cognitive Functions Unit, Paris (Bourgeron, Dumas, Cliquet, Leblond); Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (Banaschewski).
Am J Psychiatry. 2022 May;179(5):336-349. doi: 10.1176/appi.ajp.21070711. Epub 2022 Mar 25.
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is associated with significant difficulties in adaptive behavior and variation in clinical outcomes across the life span. Some individuals with ASD improve, whereas others may not change significantly, or regress. Hence, the development of "personalized medicine" approaches is essential. However, this requires an understanding of the biological processes underpinning differences in clinical outcome, at both the individual and subgroup levels, across the lifespan.
The authors conducted a longitudinal follow-up study of 483 individuals (204 with ASD and 279 neurotypical individuals, ages 6-30 years), with assessment time points separated by ∼12-24 months. Data collected included behavioral data (Vineland Adaptive Behavior Scale-II), neuroanatomical data (structural MRI), and genetic data (DNA). Individuals with ASD were grouped into clinically meaningful "increasers," "no-changers," and "decreasers" in adaptive behavior. First, the authors compared neuroanatomy between outcome groups. Next, they examined whether deviations from the neurotypical neuroanatomical profile were associated with outcome at the individual level. Finally, they explored the observed neuroanatomical differences' potential genetic underpinnings.
Outcome groups differed in neuroanatomical features (cortical volume and thickness, surface area), including in "social brain" regions previously implicated in ASD. Also, deviations of neuroanatomical features from the neurotypical profile predicted outcome at the individual level. Moreover, neuroanatomical differences were associated with genetic processes relevant to neuroanatomical phenotypes (e.g., synaptic development).
This study demonstrates, for the first time, that variation in clinical (adaptive) outcome is associated with both group- and individual-level variation in anatomy of brain regions enriched for genes relevant to ASD. This may facilitate the move toward better targeted/precision medicine approaches.
自闭症谱系障碍（ASD）是一种终身神经发育疾病，与适应行为方面的显著困难以及整个生命周期内的临床结果变化有关。一些 ASD 患者会有所改善，而另一些患者则可能没有明显变化，或出现倒退。因此，开发“个性化医疗”方法至关重要。然而，这需要了解个体和亚组层面上，贯穿整个生命周期的，导致临床结果差异的生物学过程。
作者对 483 名个体（204 名 ASD 患者和 279 名神经典型个体，年龄 6-30 岁）进行了纵向随访研究，两次评估时间点间隔约 12-24 个月。收集的数据包括行为数据（Vineland 适应行为量表-II）、神经解剖学数据（结构 MRI）和遗传数据（DNA）。ASD 患者根据适应行为的临床意义分为“增加者”、“无变化者”和“减少者”。首先，作者比较了不同结局组之间的神经解剖学特征。其次，他们检验了个体神经解剖学特征偏离神经典型神经解剖学特征是否与结局相关。最后，他们探索了观察到的神经解剖学差异的潜在遗传基础。
结局组在神经解剖学特征（皮质体积和厚度、表面积）上存在差异，包括先前与 ASD 相关的“社交脑”区域。此外，神经解剖学特征偏离神经典型特征可预测个体水平的结局。此外，神经解剖学差异与与神经解剖学表型相关的遗传过程（例如，突触发育）相关。
这项研究首次证明，临床（适应）结局的变化与大脑区域的解剖学存在群体和个体水平的差异有关，这些区域富含与 ASD 相关的基因。这可能有助于向更好的靶向/精准医疗方法转变。
