Paradox of schizophrenia genetics: is a paradigm shift occurring?

Nagafumi Doi, Yoko Hoshi, Masanari Itokawa, Takeo Yoshikawa, Tomoe Ichikawa, Makoto Arai, Chie Usui, Hirokazu Tachikawa

Genetic research of schizophrenia (SCZ) based on the nuclear genome model (NGM) has been one of the most active areas in psychiatry for the past two decades. Although this effort is ongoing, the current situation of the molecular genetics of SCZ seems disappointing or rather perplexing. Furthermore, a prominent discrepancy between persistence of the disease at a relatively high prevalence and a low reproductive fitness of patients creates a paradox. Heterozygote advantage works to sustain the frequency of a putative susceptibility gene in the mitochondrial genome model (MGM) but not in the NGM.