Language network dysfunction as a predictor of outcome in youth at clinical high risk for psychosis

Abstract

Objectives Language processing abnormalities are a hallmark feature of schizophrenia. Yet, no study to date has investigated underlying neural networks associated with discourse processing in adolescents at clinical high risk (CHR) for developing psychosis 1 1 Please note that our journal previously published the following paper with similar methodology in people at genetic high-risk for schizophrenia: Li, X., Branch, C.A., Bertisch, H.C., Brown, K., Szulc, K.U., Ardekani, B.A., DeLisi, L.E., 2007. An fMRI study of language processing in people at high genetics risk for schizophrenia. Schizophr. Res. 91: 62–72. Bhojraj, T.S., Francis, A.N., Rajarethinam, R., Eack, S., Kulkarni, S. Prasad, K.M., Montrose, D.M., Dworakowski, D., Diwadkar, V., Keshavan, M.S., 2009. Verbal fluency deficits and altered lateralization of language brain areas in individuals genetically predisposed to schizophrenia. Schizophr. Res. 115 (2009) 202–208. . Methods Forty CHR youth and 24 demographically comparable healthy controls underwent functional magnetic resonance imaging while performing a naturalistic discourse processing paradigm. We assessed differences in blood oxygenation level-dependent (BOLD) activity between task conditions (Topic Maintenance vs. Reasoning) and between groups. Furthermore, we examined the association of regional brain activity with symptom severity and social outcome at follow-up, 6 to 24 months after the scan. Results Relative to controls, CHR participants showed increased neural activity in a network of language-associated brain regions, including the medial prefrontal cortex bilaterally, left inferior frontal (LIFG; BA44/45, 47) and middle temporal gyri, and the anterior cingulate (BA24 and 32). Further, increased activity in the superior temporal gyrus (STG), caudate, and LIFG distinguished those who subsequently developed psychosis. Within the CHR sample, severity of positive formal thought disorder at follow-up was positively correlated with signal change in the LIFG, superior frontal gyrus, and inferior/middle temporal gyri, whereas social outcome was inversely correlated with signal change in the LIFG and anterior cingulate. Conclusions These findings are consistent with a neural inefficiency hypothesis in those at greatest risk for psychosis, and additionally suggest that baseline activation differences may predict symptomatic and functional outcome. These results highlight the need to further investigate the neural systems involved in conversion to psychosis, and how language disruption changes over time in at-risk adolescents.