A review of S. Hossein Fatemi, Teri J. Reutiman, Timothy D. Folsom, Paul D. Thuras (2008). GABAA Receptor Downregulation in Brains of Subjects with Autism Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-008-0646-7

Neurotransmitters are chemicals that transfer information from one neuron to another. Although we often hear about how specific neurotransmitters are associated with specific behaviors or disorders (serotonin and depression), at the most basic level, neurotransmitters do mostly two things: they tell the receiving neuron to “fire” (excitatory) or they tell the receiving neuron to stop firing (inhibitory). The neurotransmitters are able to do this because of the nature of the receptors that receive the neurotransmitter in the receiving neuron. GABA, for example, attaches to receptors that are primarily inhibitory in nature. Thus, most anti-anxiety medications work by increasing GABA transmission so more GABA receptors are activated and consequently “shutting down” the central nervous system (thus relaxation).

In this study the authors examined key GABA receptors in the brains of 8 person with autism (1 female) and 8 comparison participants (1 female) matched for age and gender. The participants range from 19 to 56 years of age. The cause of death varied, from car accidents to myocardial infarction. The authors found significant reductions in GABA receptors in the parietal cortex, cerebellum, and superior frontal cortex of the subjects with autism when compared to the control group. Most importantly, this group differences were not due to group differences in seizure disorders. The authors suggest that the noted cerebellar abnormalities may explain dysfunction with motor systems usually observed in autism, parietal cortex abnormalities may explain disturbances in visuo-spatial integration, language, and attention, and frontal cortex abnormalities may explain disruptions in emotion, cognition, and language. These findings may also explain why many parents report significant improvement when their children take anti-anxiety medications.

One note about studies using very small samples. I often see a tendency to dismiss the results of such studies because they have too few participants (“the sample size was too small”). This criticism, while valid in some cases, is most appropriate for studies that fail to find significant differences between the groups. That is, having a small sample makes it more difficult to find statistically significant differences between the groups. Thus, finding such differences in small samples (such as in this case) may speak to the robustness of the differences: The differences are so large we are able to see them even in this small sample. However, small samples are also more sensitive to unusual cases (outliers) and that the sample may be unique and not really representative of the population it is supposed to represent, thus possibly making the results less reliable (but not necessarily less real).

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2 Responses to GABA Receptors and Autism

  1. RAJ says:

    The control groups used are all wrong. According to the abstract the control group was matched on age and gender. GABA receptor dysfunction has also been reported post mortem in mental retardation (without autism) as well as schizophrenia:

    http://www.cellscience.com/reviews17/GABAA_receptors_schizophrenia.html

    There is no neurochemical abnormality reported in autism that hasn’t also been found in other neurologically impaired populations without autism.

    Neurochemical dysfunction does not appear to be specific to autism and the proper control groups should be mentally retarded and schizphrenic patients examined post mortem.

    This is the same problem with hte Autism Genome Consortium’s lack of control groups. Every single new genetic abnormality reported in a handful of cases by the Consortium has also been reported in other neurologically impaired populations without autism.

    Selecting only ‘autistic’ groups and comparing the results to normal controls matched on age and gender gives the false impression that a finding is specific to autism when it is not.

  2. Dear Raj,
    Thank you for your comment. You are 100% correct in that this data can not say anything about the specificity of this finding to Autism (as opposed to MR or other disorders). However, the issue of specificity is a completely different question. The authors of the study were not interested in addressing specificity, they were interested in exploring whether GABA receptors were associated with autism (not whether GABA receptors were associated ONLY to autism). I understand that you find “specificity” to be extremely important, and in many cases specificity is extremely important. But in psychiatry, and medicine in general, potential causal factors are not specific, and are usually associated with multiple disorders or conditions. Yet this does not negate the association between the causal factor and any single condition. For example, obesity is a risk factor for diabetes. This is a finding well replicated. Yet, obesity is not specific to diabetes, and is also associated with many other disorders. This does not negate the association between obesity and diabetes. GABA dysregulation is associated with anxiety, schizophrenia, depression, PTSD, Phobias, and even sleep disorders. GABA dysregulation is clearly not specific to any particular disorder, but this does not mean that GABA is not associated with each of these disorders.

    Again, I completely agree that this study does not address the issue of specificity. I think the authors would also agree, and likely predict, that GABA dysregulation is not specific to Autism.

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