Amygdala, autism and clinical impairment: When group comparisons are not enough.
Posted Mar 03 2009 2:53pm
Two metabolites in the amygdala are associated with clinical impairment in autism.
A review of: Natalia M. Kleinhans, Todd Richards, Kurt E. Weaver, Olivia Liang, Geraldine Dawson, Elizabeth Aylward (2009). Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger’s Disorder Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-009-0707-6
This brief yet powerful article is an example of research moving beyond making simple comparisons between typically developing children and children with autism - a move that has implications for how we conduct and evaluate etiological and mechanistic research.
In sum, the authors were interested in examining amygdala functioning in autism. The amygala serves a critical function in emotion recognition and processing, and thus it has been implicated in the neurophysiology of autism. For example, individuals with autism have been found to display atypical amygdala growth processes from childhood into adolescence (see for example Nacewiz et al., 2006. Archives of General Psychiatry, 63,12).
In this study the authors wanted to examine the biochemical integrity of the amygdala among individuals with high functioning autism and typical developing peers. In addition, the authors wanted to examine whether biochemical alterations in the amygdala would be associated with specific clinical symptoms of autism. The participants included 20 adults with high functioning autism (18 males, average age 23.57) and 19 typically developing peers (17 males, average age 23.32). Autism diagnosis was confirmed via ADOS and ADI. The Amygdale's bilateral biochemical functioning was obtained via magnetic resonance spectroscopy. Four metabolites were measured: N-acetyl aspartate (NAA), creatine/Phosphocreatine (Cre), choline (Cho), and myoinositol (ml).
The authors did not find any differences in the concentrations of any of the metabolites when comparing the HFA and the control groups. Both groups had equal levels of all the metabolites measured. However, among the individuals with HFA, NAA was significantly associated with communication impairments, as measured by the ADI. In addition, Cre and NAA were associated with restrictive interests, and Cre alone was associated with social difficulties. The results therefore, indicate that those with the lowest concentrations of these metabolites tended to have more severe clinical symptoms as reported by the ADI.
The results of this study provide support for the need to conduct examinations that go beyond simple group comparisons. In this case, the authors found no differences in any of the metabolites between the two groups, which could easily lead one to conclude that such metabolites may not play a role in autism. Yet, the results were strong in indicating that key metabolites, while observed at normative levels, play a key role in the clinical presentation of the disorder. Although this is not necessarily new, it is consistent with a paradigm shift in how etiological or mechanistic research is conducted, in that the presence of normative functioning in a particular domain or brain process (when compared to typical peers) does not necessarily indicate that such domain is not implicated in the phenomenology of the condition.