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Orbitofrontal-striatal structural alterations linked to negative symptoms at different stages of the schizophrenia spectrum

By Matthias Kirschner, André Schmidt, Benazir Hodzic-Santor, Achim Burrer, Andrei Manoliu, Yashar Zeighami, Yvonne Yau, Nooshin Abbasi, Anke Maatz, Benedikt Habermeyer, Aslan Abivardi, Mihai Avram, Felix Brandl, Christian Sorg, Philipp Homan, Anita Riecher-Rössler, Stefan Borgwardt, Erich Seifritz, Alain Dagher, Stefan Kaiser

Posted 10 Apr 2020
medRxiv DOI: 10.1101/2020.04.07.20057166

Among the most debilitating manifestations of schizophrenia are negative symptoms such as anhedonia and apathy. Imaging studies have linked these symptoms to morphometric abnormalities in two brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and ventral striatum. Negative symptoms generally are associated with reduced OFC thickness, while apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment, or an underlying phenotypic trait. Here we use multicentre MRI data to investigate orbitofrontal-striatal abnormalities across the schizophrenia-spectrum from healthy populations with schizotypy, to unmedicated and medicated first-episode psychosis patients, and patients with chronic schizophrenia. Striatal volumes and OFC thickness were estimated from T1-weighted images acquired in all three diagnostic groups and controls from four sites (n=337). Results were first established in one test cohort ("Zurich sample") and replicated in three independent samples. There was a correlation between apathy and striatal volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger striatal volumes, which appears to be a consequence of antipsychotic medications. The association between reduced OFC thickness and negative symptoms generally also appeared to vary along the disease course, being significant only in first-episode psychosis patients. In schizotypy there was increased OFC relative to controls. Our findings suggest that negative symptoms associate with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of schizophrenia. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to disease-onset.

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