ArticleSchizophrenia research2009
Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder.
Article in Schizophrenia research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 54 citations in OpenAlex.
- HCAR3 May Mediate Autism Symptoms: Evidence From RNA-Sequencing of Peripheral Blood Mononuclear Cells.Psychiatry investigation · 2025Article
- Contribution of the serotonergic system to developmental brain abnormalities in autism spectrum disorder.Autism research : official journal of the International Society for Autism Research · 2024Review
- Implications of Kynurenine Pathway Metabolism for the Immune System, Hypothalamic-Pituitary-Adrenal Axis, and Neurotransmission in Alcohol Use Disorder.International journal of molecular sciences · 2024Review
- A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension.Biomedicines · 2023Review
- Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches.Scientific reports · 2023Article
- Implication of Melanocortin Receptor Genes in the Familial Comorbidity of Type 2 Diabetes and Depression.International journal of molecular sciences · 2022Article
- The Epigenetics of Psychosis: A Structured Review with Representative Loci.Biomedicines · 2022Review
- Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits.Advanced genetics (Hoboken, N.J.) · 2020Article
- Association between IFN-γ +874 T/A (Rs2430561) Polymorphisms and Bipolar 1 Disorder: A Study in an Ethnic Iranian Population.Reports of biochemistry & molecular biology · 2019Article
- Comprehensive behavioral analysis of tryptophan 2,3-dioxygenase (Tdo2) knockout mice.Neuropsychopharmacology reports · 2018Article
- Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II Disorder: A Case of Vitamin Dependency.Nutrients · 2018Article
- Melanocortins, Melanocortin Receptors and Multiple Sclerosis.Brain sciences · 2017Review
- TDO as a therapeutic target in brain diseases.Metabolic brain disease · 2016Review
- Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression.Neuropsychiatric disease and treatment · 2015Article
- The effect of transient increases in kynurenic acid and quinolinic acid levels early in life on behavior in adulthood: Implications for schizophrenia.Schizophrenia research · 2013Article
- Family of melanocortin receptor (MCR) genes in mammals-mutations, polymorphisms and phenotypic effects.Journal of applied genetics · 2013Review
- Evidence for phenotypic plasticity in response to photic cues and the connection with genes of risk in schizophrenia.Frontiers in behavioral neuroscience · 2013Article
- Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects.Metabolic brain disease · 2012Review
- Exposure to kynurenic acid during adolescence produces memory deficits in adulthood.Schizophrenia bulletin · 2012Article
- Placental source for 5-HT that tunes fetal brain development.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Prior studies of mRNA expression, protein expression, and pathway metabolite levels have implicated dysregulation of the kynurenine pathway in the etiology of schizophrenia and bipolar disorder. Here we investigate whether genes involved in kynurenine pathway regulation might interact with genes that respond to kynurenine metabolites, to enhance risk for these psychiatric phenotypes. Candidate genes were selected from prior studies of genetic association, gene expression profiling and animal models. A single nucleotide polymorphism (SNP) in each of six genes, TDO2, HM74, HM74A, MCHR1, MCHR2 and MC5R, was tested for association with phenotype (475 Caucasians, 88 African Americans with schizophrenia; 97 Caucasians, 3 African Americans with bipolar disorder; 191 Caucasian, 49 African American controls). An A allele in HM74 was significantly associated with schizophrenia and with schizophrenia plus bipolar disorder combined, odds ratios (OR) of 1.48, p=0.011 and 1.50, p=0.007, respectively. Augmentation of disease risk was found for the complex genotype HM74[A,any]+MCHR1[T,any]+MCHR2[C,any] which conferred an OR maximal for the combined diagnostic category of schizophrenia plus bipolar disorder (1.70, p=0.003), carried by 30% of the cases. TDO2[CC]+MC5R[G, any]+MCHR2[GC] conferred an OR maximal for schizophrenia alone (4.84, p=0.005), carried by 8% of schizophrenia cases. The combined risk posed by these related, complex genotypes is greater than any identified single locus and may derive from co-regulation of the kynurenine pathway by interacting genes, a lack of adequate melanotropin-controlled sequestration of the kynurenine-derived pigments, or the production of melanotropin receptor ligands through kynurenine metabolism.
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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.