Reduced language lateralization in first-episode medication-naive schizophrenia

Diminished functional lateralization in language-related areas is found in chronic schizophrenia. It is not clear at what stage of illness these abnormalities in lateralization arise, or whether they are affected by medication. In addition, it is hypothesized that reduced language lateralization is related to positive symptoms of schizophrenia, but studies addressing this issue have yielded contradictory results. In this study we used functional MRI to measure language lateralization in 35 first-episode medication-naive schizophrenia patients and 43 matched healthy controls. Subjects performed three language tasks: a paced verb generation task, an antonym generation task, and a semantic decision task. Lateralization Index (LI) was calculated, using a relative threshold technique, in seven Regions of Interest (ROIs), including the main language-related areas and their contralateral homologues. In addition, we investigated whether language lateralization was correlated with psychotic symptoms. Across all ROIs, LI was significantly reduced in patients (p<0.001) compared to controls. Post-hoc tests revealed that this reduction was most prominent in the inferior frontal gyrus (part of Broca's area) (p=0.003) and the superior temporal gyrus (part of Wernicke's area) (p<0.001). LI was not correlated with the positive subscale of the PANSS, nor with hallucinations or disorganization. This is the first study to report reduced LI at the onset of schizophrenia, before medical treatment is initiated.