ArticleMolecular psychiatry2013
Antipsychotics activate the TGFβ pathway effector SMAD3.
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- A systematic review of antipsychotic drug effects on human gene expression related to risk factors for cardiovascular disease.The pharmacogenomics journal · 2014Pooled it
- A single-cell survey unveils cellular heterogeneity and sensitive responses in mouse cortices induced by oral exposure to triphenyl phosphate.Archives of toxicology · 2022Article
- A potent HNF4α agonist reveals that HNF4α controls genes important in inflammatory bowel disease and Paneth cells.PloS one · 2022Article
- Liver fat storage is controlled by HNF4α through induction of lipophagy and is reversed by a potent HNF4α agonist.Cell death & disease · 2021Article
- The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Article
- Diabetes and Cardiovascular Care Among People with Severe Mental Illness: A Literature Review.Journal of general internal medicine · 2016Review
- Identification of alverine and benfluorex as HNF4α activators.ACS chemical biology · 2013Article
- A novel insulin sensitizer drug candidate-BGP-15-can prevent metabolic side effects of atypical antipsychotics.Pathology oncology research : POR · 2012Article
- Recent advances in understanding and mitigating adipogenic and metabolic effects of antipsychotic drugs.Frontiers in psychiatry · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Although effective in treating an array of neurological disorders, antipsychotics are associated with deleterious metabolic side effects. Through high-throughput screening, we previously identified phenothiazine antipsychotics as modulators of the human insulin promoter. Here, we extended our initial finding to structurally diverse typical and atypical antipsychotics. We then identified the transforming growth factor beta (TGFβ) pathway as being involved in the effect of antipsychotics on the insulin promoter, finding that antipsychotics activated SMAD3, a downstream effector of the TGFβ pathway, through a receptor distinct from the TGFβ receptor family and known neurotransmitter receptor targets of antipsychotics. Of note, antipsychotics that do not cause metabolic side effects did not activate SMAD3. In vivo relevance was demonstrated by reanalysis of gene expression data from human brains treated with antipsychotics, which showed altered expression of SMAD3 responsive genes. This work raises the possibility that antipsychotics could be designed that retain beneficial CNS activity while lacking deleterious metabolic side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.