Brendon Nacewicz1, Kim M. Dalton1, Lisa A. Angelos1, Matthew J. Sutterer1, Andrew L. Alexander2, and Richard J. Davidson3. (1) Waisman Laboratory for Brain Imaging & Behavior, University of Wisconsin, Madison, WI 53705, (2) Department of Medical Physics, Department of Psychiatry, Waisman Laboratory for Brain Imaging & Behavior, University of Wisconsin, Madison, WI 53705, (3) Department of Psychology, Department of Psychiatry, Waisman Laboratory for Brain Imaging & Behavior, University of Wisconsin, Madison, WI 53705
Background:Recent work suggests abnormal amygdala development may relate to social impairments in autism. However, this is based on differences in amygdala volume and has yet to be related to underlying neural or histological differences. Magnetic Resonance Spectroscopy (MRS) holds promise for understanding differences in neurochemistry both in pathology and normal development. Initial MRS studies in adolescents with autism suggest that neurochemical differences in the medial temporal lobe may also relate to social impairments, but whether these represent amygdala or hippocampus is unclear. As a further confound, amygdala volume increases rapidly throughout adolescence and some metabolites may show similar age-related differences.
We recently developed an MRS technique that can reliably measure GABA levels specifically in amygdala. With this novel technique, we aim to characterize normal neurochemical development and to look for changes that parallel the rapid growth during this period. An understanding of normal amygdala neurochemistry will provide a reference for future studies of adolescents with autism, allowing models of hypersensitivity and hyposensitivity to be framed in terms of low and high GABA/glutamate levels.
Objectives:To characterize the typical neurochemical development of the human amygdala from age 10 to 25 using amygdala-specific MRS.
Methods:Twenty-two typically developing males aged 10-25 y were recruited in an ongoing effort to uniformly sample the age range (2 subjects per year of life). Amygdala-specific MRS was performed at 3T. Metabolite levels calculated with LCModel were corrected for acquisition volume by linear regression.
Results:Of all measured metabolites, only GABA showed a significant linear change with age (r = -0.52, p = 0.02).
Conclusions:While maturation of the amygdala during typical development includes increasing volume, GABA levels may be decreasing in this process. Future studies aiming to characterize amygdalar GABA in autism should take into account age effects.