Basal-Forebrain Cholinergic Nuclei Alterations are Associated With Medication and Cognitive Deficits Across the Schizophrenia Spectrum

Julia Schulz*, Felix Brandl, Michel J. Grothe, Matthias Kirschner, Stefan Kaiser, André Schmidt, Stefan Borgwardt, Josef Priller, Christian Sorg, Mihai Avram

*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

Background and Hypothesis: The cholinergic system is altered in schizophrenia. Particularly, patients' volumes of basal-forebrain cholinergic nuclei (BFCN) are lower and correlated with attentional deficits. It is unclear, however, if and how BFCN changes and their link to cognitive symptoms extend across the schizophrenia spectrum, including individuals with at-risk mental state for psychosis (ARMS) or during first psychotic episode (FEP). Study Design: To address this question, we assessed voxel-based morphometry (VBM) of structural magnetic resonance imaging data of anterior and posterior BFCN subclusters as well as symptom ratings, including cognitive, positive, and negative symptoms, in a large multi-site dataset (n = 4) comprising 68 ARMS subjects, 98 FEP patients (27 unmedicated and 71 medicated), 140 patients with established schizophrenia (SCZ; medicated), and 169 healthy controls. Results: In SCZ, we found lower VBM measures for the anterior BFCN, which were associated with the anticholinergic burden of medication and correlated with patients' cognitive deficits. In contrast, we found larger VBM measures for the posterior BFCN in FEP, which were driven by unmedicated patients and correlated at-trend with cognitive deficits. We found no BFCN changes in ARMS. Altered VBM measures were not correlated with positive or negative symptoms. Conclusions: Results demonstrate complex (posterior vs. anterior BFCN) and non-linear (larger vs. lower VBM) differences in BFCN across the schizophrenia spectrum, which are specifically associated both with medication, including its anticholinergic burden, and cognitive symptoms. Data suggest an altered trajectory of BFCN integrity in schizophrenia, influenced by medication and relevant for cognitive symptoms.

OriginalspracheEnglisch
ZeitschriftSchizophrenia bulletin
Jahrgang49
Ausgabenummer6
Seiten (von - bis)1530-1541
Seitenumfang12
ISSN0586-7614
DOIs
PublikationsstatusVeröffentlicht - 01.11.2023

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

DFG-Fachsystematik

  • 206-10 Klinische Psychiatrie, Psychotherapie und Kinder- und Jugendpsychiatrie

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