GLPwatch
A systematic review in effects of glucagon-like peptide-1 (GLP-1) mono-agonists on functional connectivity: Target engagement and rationale for the development in mental disorders.
J Affect Disord · 2025
Last updated 2026-05-28A review of 8 studies found that GLP-1 drugs affect brain connectivity in areas linked to mental health, such as the default mode network and amygdala. Some drugs, like exenatide, increased connectivity in certain brain regions, while others, like liraglutide, had different effects in healthy individuals. The findings suggest GLP-1 drugs may influence brain circuits involved in conditions like anhedonia.
AI summary of the abstract below.
| Journal | J Affect Disord, 2025 |
|---|---|
| Citations | 14 |
| Relative citation ratio | 5.81 |
| Molecules | — |
| Conditions studied | Depression, Anxiety, Bipolar Disorder, Alzheimers |
Abstract
INTRODUCTION: The mechanistic role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) in modulating brain functional activity has been inadequately examined. Mental disorders are characterized by dysregulated functional connectivity in brain circuits that subserve phenomenology. We conducted a comprehensive synthesis of known effects of GLP-1 and GLP-1RAs on functional connectivity.
METHODS: We conducted a systematic review examining studies that investigate changes in functional connectivity mediated by GLP-1 and GLP-1RAs in human adults. Relevant articles were retrieved from OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to April 26, 2024. Primary or secondary studies (n = 8) investigating the role of GLP-1 and GLP-1RAs on functional connectivity were included for analysis.
RESULTS: GLP-1 and GLP-1RAs modulate functional connectivity within the dorsal default mode network (DMN), visuospatial network, right frontal parietal network, and the salience network. GLP-1 agonism is also associated with decreased functional connectivity within the hypothalamus, lateral orbitofrontal cortex, and amygdala. Contrastingly, some GLP-1RAs (e.g. exenatide) increase functional connectivity in the hypothalamus, nucleus tractus solitarius, and thalamus. Moreover, liraglutide is associated with increased functional connectivity within the hippocampus in healthy individuals suggesting that GLP-1RAs may have differential effects on brain functional connectivity.
DISCUSSION: We observed that GLP-1 and GLP-1 RAs are associated with changes in functional connectivity known to subserve phenomenology of many mental disorders (e.g. anhedonia). Future research should aim to further examine neural circuits and networks affected by GLP-1 receptor activity and how they may affect cognitive and psychopathological domains in psychiatric disorders.
Verbatim abstract via PubMed 39515485 ↗