Reward deficiency syndrome: genetic aspects of behavioral disorders

Comings, David E.; Blum, Kenneth

doi:10.1016/s0079-6123(00)26022-6

Cited by 563 publications

(404 citation statements)

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“…Billet et al (1998) did not find an association in a sample of 100 OCD patients either. Since the A1 allele of the DRD2 TaqI A system has been found to be associated with a variety of addictive, impulsive and compulsive disorders, the association of the A2 allele with our OCD-sample was unexpected (Comings and Blum, 2000). In addition, we presumed a higher frequency of the A1 allele, as it has been suggested that the A1 allele is associated with a mutation that decreases the D 2 receptor expression.…”

Section: Discussionmentioning

confidence: 86%

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Denys

Nieuwerburgh

Deforce

et al. 2006

European Neuropsychopharmacology

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Background: Mounting evidence suggests the involvement of the dopamine system in the pathophysiology of obsessive-compulsive disorder. Method: The relationship of the dopamine D 2 receptor (DRD2) TaqI A, and catechol-O-methyltransferase (COMT) NlaIII High/Low activity polymorphism to obsessive-compulsive disorder (OCD) was examined in a sample of 150 patients and 150 controls. Results: OCD patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, when the sample was stratified by gender, there was a trend to a significant predominance of the DRD2 A2A2 genotype ( p = 0.049), and a higher frequency of the DRD2 A2 allele ( p = 0.020) and low-activity COMT allele ( p = 0.035) in male OCD patients compared to male controls. In addition, we observed an association of the DRD2 A2A2 genotype in patients with an early onset of disease (V15 years) ( p = 0.033). Conclusions: Our findings replicate previous reports and provide support for a potential role of the COMT and DRD2 locus in subgroup of male, early onset patients with OCD.

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Section: Discussionmentioning

confidence: 86%

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Denys

Nieuwerburgh

Deforce

et al. 2006

European Neuropsychopharmacology

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“…This syndrome is characterized by an insufficient dopamine-related natural reward that leads to the use of 'unnatural' immediate rewards, such as substance use, gambling, risk taking and inappropriate eating. 11 Several lines of evidence suggest that the patients with ADHD may present with behaviors consistent with the 'reward deficiency syndrome'. [12][13][14][15] In particular, the compromised regulation of impulses as well as the poor planning and organization described in patients with ADHD may lead to abnormal eating behaviors, such as bulimic behaviors, which, in turn, may be associated with obesity.…”

Section: Introductionmentioning

confidence: 99%

Association between symptoms of attention-deficit/hyperactivity disorder and bulimic behaviors in a clinical sample of severely obese adolescents

et al. 2006

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Objective: Preliminary evidence suggests a comorbidity between attention-deficit/hyperactivity disorder (ADHD) and obesity. This study was carried out to identify the clinical characteristics of obese adolescents with a higher probability of ADHD and advance the understanding of the potential factors underlying the comorbidity between obesity and ADHD. We evaluated the association between ADHD symptoms and bulimic behaviors, depressive and anxiety symptoms, degree of obesity, pubertal stage, age and gender in a clinical sample of obese adolescents. Design: Cross-sectional study. Subjects: Ninety-nine severely obese adolescents aged 12-17 years. Measurements: Subjects filled out the Bulimic Investigatory Test, Edinburgh, the Beck Depression Inventory and the State-Trait Anxiety Inventory for Children. Their parents completed the Conners Parent Rating Scale, which assesses ADHD symptoms. The degree of overweight was expressed as body mass index-z score. Puberty development was clinically assessed on the basis of Tanner stages. Results: Bulimic behaviors were significantly associated with ADHD symptoms after controlling for depressive and anxiety symptoms. The degree of overweight, pubertal stage, age and gender were not significantly associated with ADHD symptoms. Conclusion: Obese adolescents with bulimic behaviors may have a higher probability to present with ADHD symptoms independently from associated depressive or anxiety symptoms. The degree of overweight, pubertal stage, age and gender might not be useful for detecting obese adolescents with ADHD symptoms. Therefore, we suggest systematic screening for ADHD in obese adolescents with bulimic behaviors. Further studies are needed to understand which specific dimension of ADHD primarily accounts for the association with bulimic behaviors. Future research should also investigate the causal link between bulimic behaviors and ADHD and explore potential common neurobiological alterations. This may lead to a better understanding of the effectiveness of stimulants for the treatment of bulimic behaviors in obese subjects.

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“…We cannot rule out the possibility that the lower levels of CrϩPCr/Cho in methamphetamine users could reflect a behavioral trait liable to chronic drug usage, that is, a genetically determined "addictive personality" induced by intrinsic biochemical abnormalities may be the underlying basis of the neurochemical alterations (van den Bree et al 1998;Comings and Blum 2000). The partial volume effects of the different regions on the signals may not have been completely averted, since the basal ganglia are typically asymmetric (Watkins et al 2001).…”

Section: Discussionmentioning

confidence: 98%

Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms A Proton MRS Study

Sekine

Minabe

Kawai

et al. 2002

Neuropsychopharmacology

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Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users.In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr ϩ PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) The number of abusers of the highly addictive drug methamphetamine has risen substantially worldwide and this has raised important concerns (Woolverton et al. 1984;Baberg et al. 1996;Shaw 1999). For example, chronic methamphetamine users show psychosis and anxiety following intoxication and withdrawal (Seivewright 2000). In addition, in some individuals, these psychiatric states may be present for months or even years after cessation of methamphetamine use (Sato et al. 1992;Iwanami et al. 1994;Buffenstein et al. 1999;Iyo et al. 1999). Although there are growing clinical observations on the neurotoxicology of chronic methamphetamine use, the mechanism by which the residual psychiatric problems arise from chronic methamphetamine NO . 3 use remains unknown. In rodents and baboons, methamphetamine has been shown to be toxic to dopaminergic and serotonergic neurons (Nakayama et al. 1993;Villemagne et al. 1998;Kokoshka et al. 1998). These neurotoxic effects include decreased concentrations of dopamine and serotonin in the brain and a reduction of dopamine and serotonin transporters, as well as loss of ATP and mitochondrial dysfunction in dopaminergic neurons (Chan et al. 1994;Burrows et al. 2000;Lotharius and O'Malley 2001). Human positron emission tomography (PET) studies have reported a significant reduction of dopamine transporter density in methamphetamine users Volkow et al. 2001), and that the reduction observed in methamphetamine users is associated with psychomotor impairment (Volkow et al. 2001). Recently, we have also found that the dopamine transporter density in methamphetamine users is inversely related to the length of methamphetamine use and the magnitude of psychiatric symptoms, including psychotic symptoms (Sekine et al. 2001).In vivo proton magnetic resonance spectroscopy ( 1 H MRS) and its variant 1 H MRS techniques provide insight into the metabolism of several endogenous brain chemicals (Miller 1991;Jackson 1992). A recent 1 H MRS study showed evidence for long-term metabolite alterations in currently abstinent former methamphetamine users, that is, reduced concentration of both N-acetylaspartate (NAA) and creatine plus phosphocreatine (Cr ϩ PCr) in the right basal ganglia (Ernst et al. 2000). However, it is unclear whether these abnormalities detected by 1 H MRS are related to psychiatric symptoms that are frequently observed in abstinent methamphetamine users.In this study, we investigated changes of the chemistry in the basal ganglia of abstinent methamphetamine users by 1 H MRS, and examined any relationship between the changes and clinical cha...

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Reward deficiency syndrome: genetic aspects of behavioral disorders

Cited by 563 publications

References 118 publications

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Association between symptoms of attention-deficit/hyperactivity disorder and bulimic behaviors in a clinical sample of severely obese adolescents

Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms A Proton MRS Study

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