77. Thalamic Dysconnectivity in Individuals at Clinically High Risk for Schizophrenia and During Early Illness

Abstract

Abstract Background: Schizophrenia has been associated with thalamic hyperconnectivity with sensory regions, including the middle and superior temporal gyrus, and hypoconnectivity with cerebellar and prefrontal regions. While thalamic dysconnectivity has been consistently replicated in chronic schizophrenia samples, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset. Methods: Resting-state fMRI data were collected from clinical high-risk youth (n = 45; CHR), early illness schizophrenia (n = 74; ESZ) patients, and healthy controls (n = 85; HC). Age-adjusted whole-brain functional connectivity, seeded from the thalamus, was compared among the three groups. Main effects of group (FDR-corrected, p = .01) were followed up with Tukey-corrected pairwise comparisons. Results: Significant main effects of group were observed in 8 regions: 2 left middle temporal regions, 2 right middle temporal regions, a left superior temporal region, a right superior temporal region, a left cerebellar region, and a bilateral thalamic region. Pairwise follow-up tests (P < .05) conducted on extracted mean connectivity values revealed that, consistent with data comparing chronic schizophrenia patients to HCs, ESZ patients demonstrated greater thalamic connectivity with all middle and superior temporal regions, and reduced connectivity with cerebellar and thalamic regions. Compared to HCs, CHR youth demonstrated greater thalamic connectivity with 1 left and 1 right middle temporal region, and displayed reduced connectivity with cerebellar and thalamic regions. Compared to CHR participants, ESZ participants displayed significantly greater connectivity in all but one middle and superior temporal region, but did not differ from CHR participants in connectivity with cerebellar and thalamic regions. Conclusion: In conclusion, like chronic samples, individuals in the early stages of schizophrenia demonstrate hyperconnectivity between the thalamus and sensory regions, and hypoconnectivity with the cerebellum. Further, individuals at elevated risk for schizophrenia appear to demonstrate an intermediate level of dysconnectivity, with mean values falling between those of the early illness schizophrenia group and the healthy control group. These findings suggest that thalamic dysconnectivity occurs prior to illness onset, but is more pronounced in the early stages of schizophrenia.