The Dopamine D2 Receptor Locus as a Modifying Gene in Neuropsychiatric Disorders

De, Comings; Bg, Comings; Muhleman, Donn; Dietz, George; Shahbahrami, Bejan; Tast, D; Knell, Ellen R.; Kocsis, Pál; Baumgarten, Ruben; Bw, Kovacs

doi:10.1001/jama.1991.03470130073032

Cited by 444 publications

(146 citation statements)

References 43 publications

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“…Comings et al 58 reported an association between the Taq1 A1 allele in subjects and their diagnoses of ADHD as early as 1991. However, since then, there have been both positive and negative findings related to the putative association of the DRD2 A1 allele as a critical polymorphism linked to ADHD and related behaviors.…”

Section: The Drd2 Genementioning

confidence: 99%

“…Consequently, a positive association with the DRD2 and DRD4 polymorphisms was found in the subgroups of patients with childhood ADHD at 53.3%, or with a high impulsivity score at 73%. 58 Genetic studies have associated similar candidate genes with ADHD and tobacco-smoking phenotypes, and individuals with ADHD symptoms are at increased risk for smoking. McClernon et al 63 used multiple logistic regression analyses to examine relationships between genotype, lifetime history of habitual smoking, and self-reported ADHD symptoms in 1900 unrelated young adults.…”

Section: The Drd2 Genementioning

confidence: 99%

“…Abnormalities that result in too little or too much MAO activity have been associated with depression, 104 migraines, substance abuse, schizophrenia, ADD, 105 and inconsistent sexual maturation. 3,33,37,38,57,58 The MAO inhibitors are, therefore, one of the major drug classes prescribed for treating depression, although the risk of MAO interaction with other drugs or diet make them a last-line treatment. Excessive levels of serotonin may lead to serotonin syndrome; excessive levels of catecholamines may lead to a hypertensive crisis.…”

Section: Monoamine Oxidasesmentioning

confidence: 99%

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Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Gold¹,

Blum²,

Oscar‐Berman³

et al. 2014

Postgraduate Medicine

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Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor self-esteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with > 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.

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Section: The Drd2 Genementioning

confidence: 99%

Section: The Drd2 Genementioning

confidence: 99%

Section: Monoamine Oxidasesmentioning

confidence: 99%

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Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Gold¹,

Blum²,

Oscar‐Berman³

et al. 2014

Postgraduate Medicine

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“…The rs1800497 pathogenic variant has been previously described to associate with a reduction in DRD2 receptor density in the brain [21] and thus may be a risk factor for neuropsychiatric disorders. Many studies have also supported the association between the rs1800497 SNP and drug dependence [21–23], although others have not found such an association [24].…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have also supported the association between the rs1800497 SNP and drug dependence [21–23], although others have not found such an association [24]. …”

Section: Introductionmentioning

confidence: 99%

Association betweenANKK1(rs1800497) andLTA(rs909253) Genetic Variants and Risk of Schizophrenia

Arab

Elhawary

2015

BioMed Research International

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Limited research has assessed associations between schizophrenia and genetic variants of the ankyrin repeat and kinase domain containing 1 (ANKK1) and lymphotoxin-alpha (LTA) genes among individuals of Middle Eastern ancestry. Here we present the first association study investigating the ANKK1 rs1800497 (T>C) and LTA rs909253 (A>G) single-nucleotide polymorphisms in an Egyptian population. Among 120 patients with DSM-IV and PANSS (Positive and Negative Syndrome Scale) assessments of schizophrenia and 100 healthy controls, we determined the genotypes for the polymorphisms using endonuclease digestion of amplified genomic DNA. Results confirmed previous findings from different ethnic populations, in that the rs1800497 and rs909253 polymorphisms were both associated with risk of schizophrenia. Differences between the genotypes of cases and controls were strongly significant (P = 0.0005 for rs1800497 and P = 0.001 for rs909253). The relative risk to schizophrenia was 1.2 (P = 0.01) for the C allele and 0.8 (P = 0.04) for the G allele. The CC, GG, and combined CC/AA genotypes were all more frequent in cases than in controls. These results support an association between ANKK1 and LTA genetic markers and vulnerability to schizophrenia and show the potential influence of just one copy of the mutant C or G allele in the Egyptian population.

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Brain Serotonin and Dopamine Transporter Bindings in Adults With High-Functioning Autism

Nakamura

Sekine²,

Ouchi³

et al. 2010

Arch Gen Psychiatry

301

223

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The Dopamine D2 Receptor Locus as a Modifying Gene in Neuropsychiatric Disorders

Abstract: --These results suggest the A1 allele of the DRD2 gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

Cited by 444 publications

References 43 publications

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Association betweenANKK1(rs1800497) andLTA(rs909253) Genetic Variants and Risk of Schizophrenia

Brain Serotonin and Dopamine Transporter Bindings in Adults With High-Functioning Autism

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