High intelligence is touted as being predictive of positive outcomes including educational success and income level. However, little is known about the difficulties experienced among this population. Specifically, those with a high intellectual capacity (hyper brain) possess overexcitabilities in various domains that may predispose them to certain psychological disorders as well as physiological conditions involving elevated sensory, and altered immune and inflammatory responses (hyper body). The present study surveyed members of American Mensa, Ltd. (n = 3715) in order to explore psychoneuroimmunological (PNI) processes among those at or above the 98th percentile of intelligence. Participants were asked to self-report prevalence of both diagnosed and/or suspected mood and anxiety disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and physiological diseases that include environmental and food allergies, asthma, and autoimmune disease. High statistical significance and a remarkably high relative risk ratio of diagnoses for all examined conditions were confirmed among the Mensa group 2015 data when compared to the national average statistics. This implicates high IQ as being a potential risk factor for affective disorders, ADHD, ASD, and for increased incidence of disease related to immune dysregulation. Preliminary findings strongly support a hyper brain/hyper body association which may have substantial individual and societal implications and warrants further investigation to best identify and serve this at-risk population.