Accession Number:

ADA576717

Title:

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

Descriptive Note:

Final rept. 1 Aug 2008-31 Jul 2012

Corporate Author:

RESEARCH FOUNDATION FOR MENTAL HYGIENE INC STATEN ISLAND NY

Personal Author(s):

Report Date:

2012-08-01

Pagination or Media Count:

159.0

Abstract:

In this program project, 72 brains were examined, including 32 brains of subjects with idiopathic autism unknown etiology, 12 brains of individuals with autism associated with chromosome15 duplication dup15 and 28 brains of control subjects from 2 to 65 years of age. The study revealed several correlations between structural and biochemical changes and autistic phenotype. 1. The deficit of neuron volume detected in all 16 brain structures and 15 of 19 of their anatomical subdivisions in 4-8 year old children with autism is an indicator of global developmental encephalopathy in autism of unknown origin. Brain region-specific index of neuronal volume deficit is a sign of desynchronized development of anatomically and functionally related neurons that may explain social and communication deficits, and restricted repetitive and stereotyped patterns of behavior. Reduction of the developmental deficit from on average 19.6 in 4-8 year old to 8.8 in 8 year old subjects, indicates delayed acceleration of growth of neurons in late childhood and adulthood. The study expands corticocentric theory with evidence that autism is associated global developmental encephalopathy with delayed and desynchronized neuron growth in cortical and subcortical gray matter. 2. Abnormalities of A946 intracellular accumulation in early stage of brain development suggest their link to the clinical phenotype, including seizures, in idiopathic autism and autism associated with idic15. A946 accumulation in neurons initiates oxidative stress resulting in lipids peroxidation. Accumulation of A946 in activated astrocytes results in their death. Both are markers of developmental alterations in APP processing with structural and functional consequences. 3. Severe developmental abnormalities in the flocculus combined with reduced volume of Purkinje cells in the entire cerebellum of autistic subjects but no changes in morphology and neuronal size in the inferior olive, the second component of

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE