Handedness and schizophrenia: genetic and environmental factors

I would like to comment on the conclusions reached by Sommer et al (2001) in their meta-analysis of the literature on cerebral lateralisation and anatomical asymmetry in schizophrenia.

The article opens with the claim that: “Right-handedness, left cerebral dominance for language and normal cerebral asymmetry are considered to be secondary to a dominant allele, the ‘right-shift factor’ ” . It must be kept in mind that this is only a hypothesis and has yet to be proven. Even if the centrality of this gene were demonstrated, the influence of environmental factors would still have to be accounted for. Otherwise, it would be impossible to explain the relatively common discordance for handedness in monozygotic twins: this discordance can only be due to disruption of the intrauterine neurodevelopment in one of the twins caused by the action of environmental factors. This is supported by Steinmetz et al (1995) in which magnetic resonance imaging of twins discordant for handedness showed that this discordance is mirrored by differences in brain lateralisation. Further confirmation of the importance of environmental factors in handedness comes from a Norwegian study by Salvesen et al (1993), in which a cohort of pregnant women were divided in two groups. Half of the mothers had real ultrasound scanning during pregnancy while the others had a sham investigation. When the children were examined after birth there was significant excess of left-handedness only in the group exposed to real ultrasonography.

An interesting study by Davis & Phelps (1995) showed that the concordance for schizophrenia in monozygotic twins discordant for handedness is much higher than in twins concordant for handedness (60 v. 32%). Again, this difference can be explained only by the presence of an environmental factor acting in utero, which disrupts the neurodevelopment causing schizophrenia and altering handedness. No genetic factor can explain it.

The evidence from the literature therefore directs towards an environmental factor, which acts during neurodevelopment disrupting handedness and predisposing for schizophrenia. This hypothesis is briefly considered in the article, but then dismissed because of the results of a meta-analysis. The authors compared patients suffering from schizophrenia with patients suffering from other neuropsychiatric disorders. Both groups showed an excess of left-handedness, but in the schizophrenia population the excess was significantly higher.

The authors reached the conclusion that this shows the involvement of a genetic mechanism, but this is only one of the possible explanations. Another possibility is that there are neuropsychiatric disorders that are not neurodevelopmental in origin. Another explanation is that in certain disorders the neurodevelopmental damage acts before or after the time when handedness is established.

It is therefore my opinion that the literature on handedness and schizophrenia, comprehensively reviewed by the authors, confirms that both genetic and environmental factors have to be accounted for in the aetiology of schizophrenia. The ‘right shift’ is still only a hypothesis and the meta-analysis by Sommer et al does not corroborate or refute it.