The testosterone hypothesis: Assessment since Geschwind and Behan, 1982

The Geschwind hypothesis proposes a causal interaction among non-right-handedness, immune disorders, and learning disabilities, including dyslexia, via the intrauterine action of the male hormone testosterone. Some epidemiologic studies have supported at least a statistical association among the three traits; others have not. The associations between learning disorders and immune disease and between learning disorders and non-righthandedness appear to be better supported than that between immune disorders and non-right-handedness. However, none of data thus far accumulated are conclusive because it is not clear that the samples studied have been truly representative.The neuropathologic evidence, both in autopsy studies in human dyslexics and in animal models of developmental cortical abnormalities, are consistent with but not diagnostic of immunological pathology. Mechanisms are discussed by which an abnormal immune system could thus injure the developing brain, with an emphasis placed on abnormal maternal-fetal interactions, including maternal autoimmune disease and maternal-fetal incompatibility. A genetic origin is also possible in which the maternal role is less significant.