Genetic models for handedness, brain lateralization, schizophrenia, and manic-depression.

There has been a long-standing debate to explain the complex correlation of development of human hand preference with brain lateralization, and occasionally, the correlation of both lateralizations with psychiatric disorders. A major unanswered question in this debate is whether nature (i.e., genetics) or nurture (environment/culture) controls the development of these attributes of human behavior. Simple genetic models have failed to satisfactorily explain the mode of inheritance of psychotic disorders as well as of the handedness trait. This paper advances several hypothetical and testable genetic models to explain the complex inheritance of these traits. In one model, brain lateralization is proposed to result from nonrandom segregation of the 'Watson' and 'Crick' strands of a particular chromosome, causing hemisphere lateralization, and that a gene, designated RGHT (for right), is further proposed to be responsible for the distribution of DNA chains to specific hemispheres. Accordingly, dominant, familially inherited schizophrenia and bipolar disorders are postulated to result from chromosomal rearrangements disrupting strand segregation, while sporadic cases are proposed to occur at increased frequencies in individuals with the recessive handedness genotype. Finally, discordance in monozygotic twins is suggested to occur due to developmental differences in brain lateralization in twins of the recessive genotype. Psychotic disorders are suggested to be due to developmental anomalies of cerebral asymmetry.