Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum

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

*Korrespondierende/r Autor/-in für diese Arbeit
3 Zitate (Scopus)


Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher 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 magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.

ZeitschriftSchizophrenia bulletin
Seiten (von - bis)849-863
PublikationsstatusVeröffentlicht - 01.05.2021


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