Study of Dopamine Receptors Genes Polymorphisms in Bipolar Patients With Comorbid Alcohol Abuse

Szczepankiewicz, Aleksandra; Dmitrzak‐Węglarz, Monika; Skibińska, Maria; Słopień, Agnieszka; Leszczyńska-Rodziewicz, Anna; Czerski, Piotr M.; Hauser, Joanna

doi:10.1093/alcalc/agl106

Cited by 18 publications

(8 citation statements)

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“…The link between dopamine receptor genes and alcohol abuse comorbid with affective disorders, for example, remains controversial and may depend on the specific type of affective disorder under study (Huang et al, 2004; Huang et al, 2007; Lin et al, 2007; Szczepankiewicz et al, 2006; Young et al, 2002). …”

Section: Resultsmentioning

confidence: 99%

Genetic and environmental influences on psychiatric comorbidity: A systematic review

Cerdá¹,

Sagdeo²,

Johnson³

et al. 2010

Journal of Affective Disorders

109

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Background The purpose of this review is to systematically appraise the peer-reviewed literature about the genetic and environmental determinants of psychiatric comorbidity, focusing on four of the most prevalent types of psychopathology: anxiety disorders, depression, conduct disorder and substance abuse. Methods We summarize existing empirical research on the relative contribution that genetic, nonshared and shared environmental factors make to the covariance between disorders, and evidence about specific genes and environmental characteristics that are associated with comorbidity. Results 94 articles met the inclusion criteria and were assessed. Genetic factors play a particularly strong role in comorbidity between major depression and generalized anxiety disorder or posttraumatic stress disorder, while the non-shared environments makes an important contribution to comorbidity in affective disorders. Genetic and non-shared environmental factors also make a moderate-to-strong contribution to the relationship between CD and SA. A range of candidate genes, such as 5HTTLPR, MAOA, and DRD1-DRD4, as well as others implicated in the central nervous system, has been implicated in psychiatric comorbidity. Pivotal social factors include childhood adversity/ life events, family and peer social connections, and socioeconomic and academic difficulties. Limitations Methodological concerns include the use of clinical case-control samples, the focus on a restricted set of individual-level environmental risk factors, and restricted follow-up times. Conclusions Given the significant mental health burden associated with comorbid disorders, population-based research on modifiable risk factors for psychiatric comorbidity is vital for the design of effective preventive and clinical interventions.

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Section: Resultsmentioning

confidence: 99%

Genetic and environmental influences on psychiatric comorbidity: A systematic review

Cerdá¹,

Sagdeo²,

Johnson³

et al. 2010

Journal of Affective Disorders

109

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“…Only a single dose level of L-Dopa was examined, and associations with the gene score might differ at higher drug doses. Some genetic polymorphisms have uncertain associations with dopaminergic signaling, and negative studies have been reported for each of the polymorphisms used in the current gene score [128], [129], [130], [131]. Dopamine effects are influenced by numerous factors such as the dynamics and concentration of its release [10], [132], issues not examined in the current study.…”

Section: Discussionmentioning

confidence: 98%

Genetic Variation in the Human Brain Dopamine System Influences Motor Learning and Its Modulation by L-Dopa

et al. 2013

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Dopamine is important to learning and plasticity. Dopaminergic drugs are the focus of many therapies targeting the motor system, where high inter-individual differences in response are common. The current study examined the hypothesis that genetic variation in the dopamine system is associated with significant differences in motor learning, brain plasticity, and the effects of the dopamine precursor L-Dopa. Skilled motor learning and motor cortex plasticity were assessed using a randomized, double-blind, placebo-controlled, crossover design in 50 healthy adults during two study weeks, one with placebo and one with L-Dopa. The influence of five polymorphisms with established effects on dopamine neurotransmission was summed using a gene score, with higher scores corresponding to higher dopaminergic neurotransmission. Secondary hypotheses examined each polymorphism individually. While training on placebo, higher gene scores were associated with greater motor learning (p = .03). The effect of L-Dopa on learning varied with the gene score (gene score*drug interaction, p = .008): participants with lower gene scores, and thus lower endogenous dopaminergic neurotransmission, showed the largest learning improvement with L-Dopa relative to placebo (p<.0001), while L-Dopa had a detrimental effect in participants with higher gene scores (p = .01). Motor cortex plasticity, assessed via transcranial magnetic stimulation (TMS), also showed a gene score*drug interaction (p = .02). Individually, DRD2/ANKK1 genotype was significantly associated with motor learning (p = .02) and its modulation by L-Dopa (p<.0001), but not with any TMS measures. However, none of the individual polymorphisms explained the full constellation of findings associated with the gene score. These results suggest that genetic variation in the dopamine system influences learning and its modulation by L-Dopa. A polygene score explains differences in L-Dopa effects on learning and plasticity most robustly, thus identifying distinct biological phenotypes with respect to L-Dopa effects on learning and plasticity. These findings may have clinical applications in post-stroke rehabilitation or the treatment of Parkinson's disease.

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“…Analysis of DRD1 DdeI genotypes and the Zuckerman scores, exhibited a significant association only in men, indicating a male-limited association between the DRD1 gene polymorphism and sensationseeking score in alcohol-dependent subjects (28). The same polymorphism has not shown any significant association in both the male and the female subjects analysed (29). Furthermore, this polymorphism has shown a significant association with severity and temperament of alcohol dependence in Koreans (30).…”

Section: Drd1mentioning

confidence: 99%

Polymorphisms in genes encoding dopamine signalling pathway and risk of alcohol dependence: a systematic review

Lakkakula

Kumar

2013

Acta Neuropsychiatr.

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Study of Dopamine Receptors Genes Polymorphisms in Bipolar Patients With Comorbid Alcohol Abuse

Abstract: Our findings suggest that the analysed polymorphisms of the dopamine genes polymorphisms may not be involved in the shared genetic vulnerability to both, bipolar disorder, and alcohol abuse.

Cited by 18 publications

References 50 publications

Genetic and environmental influences on psychiatric comorbidity: A systematic review

Genetic and environmental influences on psychiatric comorbidity: A systematic review

Genetic Variation in the Human Brain Dopamine System Influences Motor Learning and Its Modulation by L-Dopa

Polymorphisms in genes encoding dopamine signalling pathway and risk of alcohol dependence: a systematic review

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