Atypical handedness in schizophrenia: some methodological and theoretical issues.

An updated review of the literature strongly supports the view that in schizophrenia there is an atypical leftward shift in the handedness distribution that, while comprising different subtypes, is characterized by a more variable and less completely lateralized pattern of manual preference, referred to as mixed handedness (MH) or ambiguous handedness (AH). Only two studies revealed an increased prevalence of left-handedness suggestive of pathological left-handedness (PLH). This article also examines the current status of neurodevelopmental factors and mechanisms in schizophrenia that purport to explain these pathological shifts in handedness (PLH, MH, AH). Different theoretical positions were evaluated, each involving some aspect of left hemisphere insult (unilateral or bilateral). Finally, it was shown that these shifts predict certain key symptoms and neural substrates in schizophrenia including thought disorder, negative symptoms, neuropsychological impairment, family history, and brain anatomy. These subtypes may represent neurodevelopmental markers of insult during intrauterine life that are nongenetic in origin.