There is a long-standing and frequently established correlation between intellectual giftedness and creativity, and neuropsychiatric disease (Andreasen and Canter, 1974, Crespi, 2016, Gardner et al., 2020). This relationship was first formally identified by Andreasen et al. based on studies of the participants in a highly competitive Creative Writing Masters of Fine Arts degree program. Gifted writers were found to have significantly more relatives with neuropsychiatric illness and showed increased rates of neuropsychiatric symptoms, although not necessarily diagnoses, compared to controls (Andreasen & Canter, 1974). The relationship between these traits appears counterintuitive, and there is currently not an established explanation for the co-occurrence of increased ability and potentially debilitating neuropsychiatric dysfunction. One potential interpretation is that the same neurobiological changes are associated with both these conditions in an inverse-U relationship. In this model the same mechanism or group of mechanisms confers an increasing advantage up to a certain threshold, but becomes pathological past that point (Fig. 1).

While an overall relationship between highly creative and intellectual subjects and a family history of neuropsychiatric illness has been established, prior studies have largely been small and highly exploratory. These studies also utilize a wide variety of definitions of both ability and neuropsychiatric illness. In order to study this relationship systematically, a more rigorous definition is needed. So-called twice exceptional individuals, first identified in educational studies of giftedness, constitute a relatively clearly defined group expressing both increased cognitive abilities and neuropsychiatric disorders (Andreasen and Canter, 1974, Assouline et al., 2012, Cain et al., 2019).

This review will discuss how the twice-exceptional population, a term originating in educational research around gifted and learning-disabled students more generally, can be used along with existing neuroimaging research into autism spectrum disorder to frame investigations of physiological links between cognitive abilities and neuropsychiatric illness. We will focus primarily on intellectually gifted subjects with ASD, as there is an established literature on variation in IQ, and a small body of neuroimaging literature revolving around subjects with both ASD and high IQ. Of note, while findings in these samples do not necessarily appear as sufficient to address questions pertaining to the neurobiology of twice-exceptionality itself, the respective results will provide a basis for generating testable hypotheses and designing future studies in twice-exceptional populations.