Excess of non-right-handedness in schizophrenia: Meta-analysis of gender effects and potential biases in handedness assessment

Abstract

Background: The notion that schizophrenia is characterised by increased non-right-handedness is a cornerstone of the theory that schizophrenia arises from, and is genetically linked to, abnormal brain lateralisation. Reviews and meta-analyses have reported higher rates of non-right-handers in patients with schizophrenia. However, this was suggested to be the result of a gender artefact or a hidden bias in self-report handedness questionnaires. Aims: To investigate using a meta-analytical approach whether the excess of non-right-handedness is seen in both females and males, and also when handedness is assessed behaviourally. Method: Electronic databases were searched for studies that reported (a) the rate of female and male non-right-handers in schizophrenia compared with controls and (b) the rate of non-right-handers in schizophrenia (regardless of gender) based on behavioural handedness assessment. Results: The odds ratios (ORs) for females (OR = 1.63; based on 621 patients, 3747 controls) and males (OR = 1.50; based on 1213 patients, 3800 controls) differed significantly from 1.0, indicating both female and male patients were more often non-right-handed than controls. Moreover, there was an excess of non-right-handedness in patients with schizophrenia when handedness was assessed behaviourally: OR = 1.84 (1255 patients, 6260 controls). Even when both gender and behavioural handedness assessment were controlled for simultaneously, the excess of non-righthandedness persisted. Conclusions: The findings clearly demonstrate that the excess of non-right-handedness in schizophrenia does not result from a gender artefact or from biased handedness questionnaires. It is a true empirical effect and may indeed reflect a genetic link between schizophrenia and brain lateralisation.