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The effect of glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide receptor agonists on neurogenesis, differentiation, and plasticity (Neuro-GDP): potential mechanistically informed therapeutics in the treatment and prevention of mental disorders
McIntyre RS, Rasgon N, Goldberg J, Wong S, Le GH, Mansur RB, Rosenblat JD, Teopiz KM et al.. CNS spectrums, 2025-02-18
Topic: Brain proteins, microglia and lab models
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RAs) mimic naturally occurring GLP-1 and GIP and are highly effective anti-diabetic and anti-obesity agents. In addition to their robust acute and long-term effects on weight, metabolism, and blood pressure, these agents also reduce cardiovascular mortality as well as stroke risk and associated consequences. A replicated and convergent body of preclinical evidence also indicates that incretin receptor agonists activate molecular effectors critical to neuroplasticity, neuroprotection, and anti-apoptosis. Herein, we propose that GLP-1 RAs and GIP RAs are promising transdiagnostic mechanistically informed therapeutics in the treatment and prevention of multiple domains of psychopathology, including general cognitive, reward, and motivation systems and mental disorders. Major neurocognitive disorders (eg, Alzheimer's Disease, Parkinson's Disease), alcohol and substance use disorders, traumatic brain injury, and depressive disorders are near-term therapeutic targets. In addition, GLP-1 RAs and GIP RAs have robust effects on comorbidities that differentially affect persons with mental disorders (eg, cardiovascular, cerebrovascular, and metabolic disorders) and psychotropic drug-related weight gain.
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APA 7th
McIntyre, R. S., Rasgon, N., Goldberg, J., Wong, S., Le, G. H., Mansur, R. B., et al. (2025). The effect of glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide receptor agonists on neurogenesis, differentiation, and plasticity (Neuro-GDP): potential mechanistically informed therapeutics in the treatment and prevention of mental disorders. CNS spectrums. https://doi.org/10.1017/s1092852925000124
Vancouver
McIntyre RS, Rasgon N, Goldberg J, Wong S, Le GH, Mansur RB, et al. The effect of glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide receptor agonists on neurogenesis, differentiation, and plasticity (Neuro-GDP): potential mechanistically informed therapeutics in the treatment and prevention of mental disorders. CNS spectrums. 2025. doi:10.1017/s1092852925000124. PMID: 39964126.
BibTeX
@article{mcintyre2025-39964126,
author = {McIntyre, R. S. and Rasgon, N. and Goldberg, J. and Wong, S. and Le, G. H. and Mansur, R. B. and Rosenblat, J. D. and Teopiz, K. M. and others},
title = {{The effect of glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide receptor agonists on neurogenesis, differentiation, and plasticity (Neuro-GDP): potential mechanistically informed therapeutics in the treatment and prevention of mental disorders}},
journal = {CNS spectrums},
year = {2025},
doi = {10.1017/s1092852925000124},
pmid = {39964126},
url = {https://doi.org/10.1017/s1092852925000124}
}
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Key findings
- A replicated and convergent body of preclinical evidence also indicates that incretin receptor agonists activate molecular effectors critical to neuroplasticity, neuroprotection, and anti-apoptosis.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (CNS spectrums) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39964126) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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