ArticleSchizophrenia bulletin2016
Increased Nigral SLC6A3 Activity in Schizophrenia Patients: Findings From the Toronto-McLean Cohorts.
Article in Schizophrenia bulletin, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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
11 citing papers in PubMed, 12 citations in OpenAlex.
- Presence of recombination hotspots throughout SLC6A3.PloS one · 2019Trial
- Role of Glial Trace Amine Associated Receptor 1 (TAAR1) and Microbiota in Schizophrenia.Neurochemical research · 2025Review
- Stable Dopamine-Signaling mRNA Co-Expression in the Substantia Nigra Is Deregulated in Pathological Conditions, but Not in Dopamine Transporter Knockout Rats.Biomolecules · 2025Article
- Association ofFrontiers in psychiatry · 2023Article
- The dopamine transporter gene SLC6A3: multidisease risks.Molecular psychiatry · 2022Article
- Epistatic evidence for gender-dependant slow neurotransmission signalling in substance use disorders: PPP1R12B versus PPP1R1B.EBioMedicine · 2020Article
- Short-active photoperiod gestation induces psychiatry-relevant behavior in healthy mice but a resiliency to such effects are seen in mice with reduced dopamine transporter expression.Scientific reports · 2020Article
- Intragenic Transcriptional cis-Antagonism Across SLC6A3.Molecular neurobiology · 2019Article
- Article
- Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference.Scientific reports · 2017Article
- hVMAT2: A Target of Individualized Medication for Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
SLC6A3, which encodes the primary regulator of extracellular dopamine (DA) concentration, the DA transporter, has been implicated in schizophrenia (SCZ). However, the details of its genetic effect on risk remain largely unknown. The purpose of this candidate gene study was to identify a specificSLC6A3activity associated with SCZ by using functional genetic approaches. We first examined gene activity in DA neurons isolated from case-control postmortem nigral tissue and found that the averageSLC6A3mRNA level in controls was only 0.37-fold of that in cases (P= .0034). To understand this expression difference, we examined the association of 10 genetic markers, mostly located in the promoter region, with SCZ in 1717 subjects collected from Toronto and McLean cohorts, including 881 controls and 836 cases and identified the 5' promoter SNP rs1478435 as having a significant association signal (uncorrectedPvalue: .00462; adjustedPvalue: .0319) in unrelated Caucasians. Allele T was over-represented in controls (OR = .75); T-carrier controls had decreased mRNA levels in nigral DA neurons, contributing to the reduced activity in the controls. In vitro functional analysis confirmed that T carriers displayed attenuated enhancement of promoter activity. These findings collectively suggest that increased nigralSLC6A3activity may be a risk factor for SCZ, and may help to explain high rates of comorbidity with substance abuse.
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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.