Publication:
Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia.

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Date

2021-12

Authors

Avram, Mihai
Grothe, Michel J
Meinhold, Lena
Leucht, Claudia
Leucht, Stefan
Borgwardt, Stefan
Brandl, Felix
Sorg, Christian

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Nature Publishing Group
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Abstract

A potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients' attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)-based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients' impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients' attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN.

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MeSH Terms

Basal Forebrain
Cholinergic Agents
Cognition
Humans
Magnetic Resonance Imaging
Schizophrenia

DeCS Terms

Pacientes
Esquizofrenia
Colinérgicos
Metronidazol
Sustancia gris
Prosencéfalo basal
Cognición

CIE Terms

Keywords

Brain, Experimental models of disease

Citation

Avram M, Grothe MJ, Meinhold L, Leucht C, Leucht S, Borgwardt S, et al. Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia. Neuropsychopharmacology. 2021 Dec;46(13):2320-2329.