The Development of Brain Anatomy and Connectivity in Males and Females with Autism Spectrum Disorder during Adolescence

• Applicant: Professorin Christine Ecker, Ph.D.
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; General, Cognitive and Mathematical Psychology ; Human Cognitive and Systems Neuroscience
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271513085

Autism Spectrum Disorder (ASD) is a life-long neurodevelopmental disorder characterized by deficits in social reciprocity, social communication, and repetitive/stereotypic behaviours. While there is considerable heterogeneity among individuals with ASD, both causative and phenotypic, research agrees that ASD is accompanied by an atypical trajectory of brain maturation and altered brain connectivity. The atypical neurodevelopmental trajectory during early childhood is well characterized in ASD. However, the neurobiological mechanisms that mediate brain maturation during adolescence in ASD remain poorly understood. It is now widely accepted that the brain continues to mature through adolescence until early adulthood, particularly in late maturing frontal and temporal lobe systems, which play a crucial role in the development of the social and emotional behaviors typically impaired in ASD. Adolescence is also a time where the course for adult neurodevelopment and behavior is set. Insights into the respective neuropathology of ASD during early adolescence could therefore provide important predictive information for the development of clinical outcomes during late adolescence and early adulthood. The first main aim of the proposed research is thus to establish the neuropathological mechanisms mediating brain maturation from late childhood to early adulthood in ASD, and to develop early adolescence biomarkers that could predict clinical outcomes during late adolescence. Preliminary evidence also suggests that ASD manifests differently as a function of biological sex, and that males and females with ASD differ in terms of their respective behavioural and neuropathological phenotypes. However, it is currently unknown whether adolescence exerts a differential effect on the neuropathology and symptom profiles in males and females with ASD, compared to neurotypical controls. The second aim of the study is thus to establish the extend to which the cortical pathology and neurodevelopmental trajectory of ASD during adolescence is modulated by biological sex, and to examine potential neuroprotective factors in adolescence that could modulate the severity of autistic symptoms in early adulthood. The outcomes of our proposed work will provide important novel insights into the neuropathology of ASD during adolescence, and elucidate gender-differences in the neurobiological and clinical ASD phenotype, which may inform future approaches to diagnosing and treating ASD during adolescence. Most importantly, however, our research will significantly contribute to the development of early in vivo biomarkers for ASD that could be utilized in the prediction of clinical outcomes later on, and thus adds to ongoing global research efforts towards translating research findings into clinical practice.

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Cooperation Partners: Professor Andre Marquand, Ph.D.; Professor Declan Murphy
• Co-Investigators: Professor Dr. Ralf Deichmann; Professorin Dr. Christine Margarete Freitag