Hemispheric lateralization of semantic processing before and after aripiprazole treatment in first-episode psychosis or ultra-high risk state

Whether aberrant language-related lateralization can be improved after antipsychotic treatment in drug-free patients with first-episode psychosis or ultra-high risk state is little known. We aimed to investigate the improvement in lateralization of semantic processing after antipsychotic treatment and associated clinical and cognitive changes. Twenty-one drug-free patients with first-episode psychosis or ultra-high risk state underwent functional magnetic resonance imaging with a semantic task, neuropsychological testing, and clinical assessments with the Positive and Negative Syndrome Scale before and after 6 weeks of aripiprazole treatment. A lateralization index of the region of interest, i.e., inferior frontal gyrus, was calculated and correlated with the behavioral indices of the semantic task, Positive and Negative Syndrome Scale scores, and language-related neuropsychological test scores. After treatment, the lateralization index of the inferior frontal gyrus was significantly increased, which was related to reduced activation of the right inferior frontal gyrus. The increase in the lateralization index was significantly associated with the increase in verbal fluency score. A higher baseline accuracy of the semantic task was associated with a higher post-treatment lateralization index of the inferior frontal gyrus and greater improvement of the total score and positive subscore of the Positive and Negative Syndrome Scale. Our findings indicated aripiprazole treatment significantly increased semantic processing-related lateralization in the inferior frontal gyrus in drug-free patients with first-episode psychosis or ultra-high risk state. A higher baseline accuracy might predict a higher post-treatment lateralization index and greater symptom improvement.