An immunoreactive theory of selective male affliction

TLDR

Males are selectively afflicted with neurodevelopmental and psychiatric disorders of childhood, a widespread phenomenon that has not received adequate biological attention, and existing literature citing psychosocial, genetic, and male complexity factors is insufficient to explain it. The study proposes that the male fetus’s antigenicity triggers maternal immunoreactivity, creating an inhospitable uterine environment that contributes to selective male affliction. The mechanism posits that male fetal antigenicity induces maternal immunoreactivity, which, together with genotype–environment interactions and pregnancy complications, drives the higher incidence of neurodevelopmental disorders in males. The immunoreactive theory (IMRT) aligns with negative parity effects in pregnancy complications and certain neurodevelopmental disorders, and although speculative, it is heuristic with some hypotheses confirmed by existing literature and the authors’ research.

Abstract

Abstract Males are selectively afflicted with the neurodevelopmental and psychiatric disorders of childhood, a broad and virtually ubiquitous phenomenon that has not received proper attention in the biological study of sex differences. The previous literature has alluded to psychosocial differences, genetic factors and elements pertaining to male “complexity” and relative immaturity, but these are not deemed an adequate explanation for selective male affliction. The structure of sex differences in neurodevelopmental disorders is hypothesized to contain these elements: (1) Males are more frequently afflicted, females more severely; (2) disorders arising in females are largely mediated by the genotype; in males, by a genotype by environment interaction; (3) complications of pregnancy and delivery occur more frequently with male births; such complications are decisive and influence subsequent development. We hypothesize that there is something about the male fetus that evokes an inhospitable uterine environment. This “evocative principle” is hypothesized to relate to the relative antigenicity of the male fetus, which may induce a state of maternal immunoreactivity, leading either directly or indirectly to fetal damage. The immunoreactive theory (IMRT) thus constructed is borrowed from studies of sex ratios and is the only explanation consistent with negative parity effects in the occurrence of pregnancy complications and certain neurodevelopmental disorders. Although the theory is necessarily speculative, it is heuristic and hypotheses derived from it are proposed; some are confirmed in the existing literature and by the authors' research.