Cortical Thinning in Temporo-Parietal Junction (TPJ) in Non-Affective First-Episode of Psychosis Patients with Persistent Negative Symptoms

Background: Negative symptoms represent an unmet therapeutic need in many patients with schizophrenia. In an extension to our previous voxel-based morphometry findings, we employed a more specific, vertex-based approach to explore cortical thinning in relation to persistent negative symptoms (PNS) in non-affective first-episode of psychosis (FEP) patients to advance our understanding of the pathophysiology of primary negative symptoms. Methods: This study included 62 non-affective FEP patients and 60 non-clinical controls; 16 patients were identified with PNS (i.e., at least 1 primary negative symptom at moderate or greater severity sustained for at least 6 consecutive months). Using cortical thickness analyses, we explored for differences between PNS and non-PNS patients as well as between each patient group and healthy controls; cut-off threshold was set at p<0.01, corrected for multiple comparisons. Results: A thinner cortex prominently in the right superior temporal gyrus extending into the temporo-parietal junction (TPJ), right parahippocampal gyrus, and left orbital frontal gyrus was identified in PNS patients vs. non-PNS patients. Compared with healthy controls, PNS patients showed a thinner cortex prominently in the right superior temporal gyrus, right parahippocampal gyrus, and right cingulate; non-PNS patients showed a thinner cortex prominently in the parahippocampal gyrus bi-laterally. Conclusion: Cortical thinning in the early stages of non-affective psychosis is present in the frontal and temporo-parietal regions in patients with PNS. With these brain regions strongly related to social cognitive functioning, our finding suggests a potential link between primary negative symptoms and social cognitive deficits through common brain etiologies.