A118G Polymorphism of OPRM1 Gene is Associated with Schizophrenia

Šerý, Omar; Přikryl, Radovan; Častulík, Lukáš; Šťastný, F

doi:10.1007/s12031-010-9327-z

Cited by 28 publications

(24 citation statements)

References 18 publications

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“…P < 0.00001 A group of Czech authors found that the rs1799971 polymorphism of the OPRM1 gene was associated with increased risk of SZ in the male population [51]. However, our results show that the probability of having SZ for those with the G variant of rs1799971 and rs2075572 was decreased, compared to people carrying the A-allele and C-allele, suggesting that the “G” allele of rs1799971 and rs207557 might have a protective effect against SZ.…”

Section: Discussioncontrasting

confidence: 67%

“…The methods used in individual studies, may have limited power to detect a small effect, or small interactions with other relevant polymorphisms. Limited sample size, etiological heterogeneity and clinical heterogeneity may result in inconsistent results showing different associations between the OPRM1 gene and SZ [18,33,51], and therefore, the conclusion of this study may be viewed in this context. Further investigations using larger sample sizes and family-based studies will undoubtedly add further valuable insight into the implications of the relationship between OPRM1 gene polymorphisms and SZ.…”

Section: Discussionmentioning

confidence: 99%

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Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population

et al. 2013

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BackgroundThe expression of μ-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of μ-opioid receptor gene (OPRM1) with SZ were inconsistent.MethodsWe conducted a case–control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP.ResultsOf four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR = 0.46, 95% CI: 0.357-0.59, P < 0.01) and 0.7-fold risk (OR = 0.707, 95% CI: 0.534-0.937, P = 0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR = 0.309, 95% CI: 0.218-0.439 for G allele, P < 0.01), and rs2075572 only in females (OR = 0.399, 95% CI: 0.246-0.648 for G allele, P < 0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR = 0.086, 95% CI: 0.048-0.151, P = 0.01; OR = 0.083, 95% CI: 0.045-0.153, P < 0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR = 0.468, 95% CI: 0.309-0.71, P < 0.01; OR = 0.34, 95% CI: 0.195-0.593, P < 0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P < 0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P < 0.01).ConclusionsThe present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.

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Section: Discussioncontrasting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population

et al. 2013

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“…Clinical data implicate the opioid system in schizophrenia [151] and borderline personality disorder [152], two conditions involving dysregulation of emotional and reward processes. At present, however, animal models of bipolar or borderline personality disorders, or affective dimensions of schizophrenia, are poorly characterized.…”

Section: Outstanding Questionsmentioning

confidence: 99%

Opioid receptors: distinct roles in mood disorders

Lutz¹,

Kieffer²

2013

Trends in Neurosciences

425

352

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The roles of opioid receptors in pain and addiction have been extensively studied, but their function in mood disorders has received less attention. Accumulating evidence from animal research reveal that mu, delta and kappa opioid receptors (MORs, DORs and KORs, respectively) exert highly distinct controls over mood-related processes. DOR agonists and KOR antagonists have promising antidepressant potential, whereas the risk-benefit ratio of currently available MOR agonists as antidepressants remain difficult to evaluate, in addition to their inherent abuse liability. At present, both human and animal studies have mainly examined MORs in the etiology of depressive disorders, and future studies will address delta and kappa receptor function in established and emerging neurobiological aspects of depression, including neurogenesis, neurodevelopment and social behaviors.

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“…Might oxytocin in autistics subserve, to some degree, positive reinforcement of non-social stimuli, or might epigenetically-based reduction of oxytocin receptor expression (Gregory et al 2009) follow from early social-19 interaction deficits? The µ-opioid system represents another important candidate mechanism, in addition to oxytocin, for neuroendocrine regulation of attachment, given links of allelic variants in the υ-opioid receptor gene OPRM1 with attachment patterns, sensitivity to social rejection, drug dependence, and risk of schizophrenia (Insel 2003;Barr et al 2008;Way et al 2009;Mague and Blendy 2010;Serý et al 2010) and evidence for parent of origin effects influencing phenotypic effects from this gene (Lemire 2005). …”

Section: Autism and Attachmentmentioning

confidence: 99%

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

Crespi

2011

Brain, Behavior and Epigenetics

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I describe and evaluate the hypothesis that effects from parent-offspring conflict and genomic imprinting on human neurodevelopment and behavior are central to evolved systems of mother-child attachment. The psychological constructs of Bowlby's attachment theory provide phenomenological descriptions of how attachment orchestrates affective-cognitive development, and patterns of imprinted gene expression and co-expression provide evidence of epigenetic and evolutionary underpinnings to human growth and neurodevelopment. Social-environmental perturbations to the development of normally-secure attachment, and alterations to evolved systems of parent-offspring conflict and imprinted-gene effects, are expected to lead to specific forms of maladaptation, manifest in psychiatric conditions affecting social-brain development. In particular, under-development of the social brain in autism may be mediated in part by mechanisms that lead to physically enhanced yet psychologically under-developed attachment to the mother, and affective-psychotic conditions, such as schizophrenia and depression, may be mediated in part by forms of insecure attachment and by increased relative effects of the maternal brain, both directly from mothers and via imprinted-gene effects in offspring. These hypotheses are concordant with findings from epidemiology, attachment theory, psychiatry, and genetic and epigenetic analyses of risk factors for autism and affective-psychotic conditions, they make novel predictions for explaining the causes of psychosis in Prader-Willi syndrome and idiopathic schizophrenia, and they suggest avenues for therapeutic interventions based on normalizing alterations to epigenetic networks and targeting public-health interventions towards reduction of perturbations to the development of secure attachment in early childhood and individuation during adolescence.

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A118G Polymorphism of OPRM1 Gene is Associated with Schizophrenia

Cited by 28 publications

References 18 publications

Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population

Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population

Opioid receptors: distinct roles in mood disorders

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

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