RECENT DEVELOPMENTS IN THE PATHOGENESIS OF AUTISTIC DISORDER: GENETICS MEETS THE IMMUNE SYSTEM

Speaker

Prof. Antonio Persico
Associate Professor in Physiology
Faculty of Medicine
Univ. “Campus Bio-Medico”
Rome, Italy;
Chief, Lab. of Mol. Psychiatry & Neurogenetics

Time

3-4pm, Thursday, June 12

Location

Room 517, new Life Science Building, Peking University

Abstract

• Objective: We shall summarize our recent results supporting the coexistence of a genetic predisposition and aberrant immune responses in autism.

• Methods: We have performed (a) the characterization of clinical, morphological, and biochemical correlates of macrocephaly in autism, (b) genetic and phenotypic studies of the PON1 and SLC25A12 genes, (c) microarray studies of total RNA and genomic DNA extracted from post-mortem tissues samples of superior temporal gyrus (BA41/42, 22 or 52), belonging to 10 pairs of autistic patients and matched controls.

• Results: (a) Macrocephaly is not an autistic endophenotype per se, but it is most often part of a broader macrosomic endophenotype, characterized by highly significant correlations between head circumference, weight and height; larger head sizes are also significantly associated with a positive history of allergic/immune disorders both in the patient and in his/her first-degree relatives; (b) serum PON1 arylesterase activity is significantly reduced in autistic patients, as typically occurs during an active immune response. SLC25A12 studies unveil elevated calcium levels in autistic brains; (c) microarray studies provide strong indications of an important immune activation and of genomic instability in the brain of several autistic patients.

• Conclusion: Our studies provide converging evidence strongly supporting the existence of pathogenetic links between a genetic predisposition and an abnormal immune response in autistic patients.