ArticleTranslational psychiatry2016
Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder.
Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- Sparse neuronal C4 elevation induces network-wide transcriptomic and lipid-droplet remodeling in the cortical microenvironment.PLoS computational biology · 2026Article
- A proof-of-concept study: investigating the impact of COMT genotype and proline on negative symptoms in Alzheimer's disease.BJPsych open · 2025Article
- Neurological Insights into 16p11.2- And 22q11.2-Related Disorders: A Mini-Review.Current genomics · 2025Review
- Comprehensive Analysis of the Microbiome and Metabolome: Unveiling Interactions Between Intestinal Flora and Metabolites in Schizophrenia.Neuropsychiatric disease and treatment · 2025Article
- The relationship between COMT, proline, and negative symptoms in clinical high risk and recent psychosis onset.Translational psychiatry · 2024Article
- Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia.World journal of psychiatry · 2024Article
- Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes.Biomolecules · 2024Article
- Patient Brain Organoids Identify a Link between the 16p11.2 Copy Number Variant and theACS chemical neuroscience · 2023Article
- DNA Methylation Pattern of Gene Promoters of MB-COMT, DRD2, and NR3C1 in Turkish Patients Diagnosed with Schizophrenia.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2022Article
- [Variations in fecal microbiota of first episode schizophrenia associated with clinical assessment and serum metabolomics].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2022Article
- A comprehensive analysis of copy number variation in a Turkish dementia cohort.Human genomics · 2021Article
- Personalised therapeutic management of epileptic patients guided by pathway-driven breath metabolomics.Communications medicine · 2021Article
- Cannabis and Psychosis Through the Lens of DSM-5.International journal of environmental research and public health · 2019Review
- Deletion size analysis of 1680 22q11.2DS subjects identifies a new recombination hotspot on chromosome 22q11.2.Human molecular genetics · 2018Article
- Genetics of Aggression in Alzheimer's Disease (AD).Frontiers in aging neuroscience · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val(158)Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions.
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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.