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The ?-opioid receptor gene A118G polymorphism is associated with insecure attachment in children with disruptive mood regulation disorder and their mothers.

ABSTRACT: BACKGROUND:The A118G single nucleotide polymorphism (SNP) of the ?-opioid receptor gene, with high expression of the A allele and low expression of the G allele, has been associated with emotional/behavioral dysregulation and depressive disorders and is recognized as a mediator of affiliative behavior. No study has thus far investigated this SNP in school-age children with disruptive mood regulation disorder (DMDD). This study compared a sample of healthy children and their mothers with a sample of children with DMDD and their mothers, evaluating whether insecure attachment and psychopathological symptoms are associated with A allele- or G allele-carrying mothers and children and whether caregiving capacities are associated with A allele- or G allele-carrying mothers. METHODS:For evaluation of their psychopathological symptoms and attachment styles, mothers filled out the CBCL/6-18, the SCL-90-R, and the ECR. To evaluate the types of relationship children were experiencing with their mothers, children filled out the ECR-revised child version and the PBI. Genotypic analyses were conducted on DNA samples obtained by buccal swabbing from children and mothers. RESULTS:An insecure attachment style was more frequent in mothers and children carrying the G allele (G/G + A/G genotypes). In the clinical sample, G allele-carrying children scored higher than homozygous A/A ones on the subscales of Withdrawal and Conduct Problems. G-carrying mothers showed higher interpersonal sensitivity, depression, hostility, and paranoid ideation and provided less care than A/A mothers. CONCLUSIONS:This study offers new insights into the associations between the A118G SNP of the ?-opioid receptor gene and emotional/behavioral functioning, attachment style in children, and psychopathology and caregiving ability in mothers.

SUBMITTER: Cimino S

PROVIDER: S-EPMC7375094 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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The μ-opioid receptor gene A118G polymorphism is associated with insecure attachment in children with disruptive mood regulation disorder and their mothers.

Cimino Silvia S Carola Valeria V Cerniglia Luca L Bussone Silvia S Bevilacqua Arturo A Tambelli Renata R

Brain and behavior 20200518 7

<h4>Background</h4>The A118G single nucleotide polymorphism (SNP) of the μ-opioid receptor gene, with high expression of the A allele and low expression of the G allele, has been associated with emotional/behavioral dysregulation and depressive disorders and is recognized as a mediator of affiliative behavior. No study has thus far investigated this SNP in school-age children with disruptive mood regulation disorder (DMDD). This study compared a sample of healthy children and their mothers with ...[more]

PMID: 32424914

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Project description:Mu-opioid receptors (MOPRs) are critically involved in the modulation of pain and analgesia, and represent a candidate mechanism for the development of biomarkers of pain conditions and their responses to treatment. To further understand the human implications of genetic variation within the opioid system in pain and opioid-mediated placebo responses, we investigated the association between the functional single-nucleotide polymorphism (SNP) in the μ-opioid receptor gene (OPRM1), A118G, and psychophysical responses, personality traits, and neurotransmitter systems (dopamine (DA), opioid) related to pain and placebo analgesia. OPRM1 G carriers, compared with AA homozygotes, showed an overall reduction of baseline μ-opioid receptor availability in regions implicated in pain and affective regulation. In response to a sustained painful stimulus, we found no effect of A118G on pain-induced endogenous opioid release. Instead, AA homozygotes showed a blunted DA response in the nucleus accumbens (NAc) in response to the pain challenge. After placebo administration, G carriers showed more pronounced mood disturbances and lower placebo-induced μ-opioid system activation in the anterior insula (aINS), the amygdala (AMY), the NAc, the thalamus (THA), and the brainstem, as well as lower levels of DA D2/3 activation in the NAc. At a trait level, G carriers reported higher NEO-Neuroticism scores; a personality trait previously associated with increased pain and lower placebo responses, which were negatively correlated with baseline μ-opioid receptor availability in the aINS and subgenual anterior cingulate cortex (sgACC). Our results demonstrate that the A118G OPRM1 polymorphism contributes to interindividual variations in the function of neurotransmitters responsive to pain (endogenous opioid and dopamine), as well as their regulation through cognitive-emotional influences in the context of therapeutic expectations, the so-called placebo effect. These effects are relevant to human vulnerability to disease processes where these neurotransmitters have a role, such as persistent pain, mood, and substance use disorders, and responses to their treatments.

Dataset Information

The ?-opioid receptor gene A118G polymorphism is associated with insecure attachment in children with disruptive mood regulation disorder and their mothers.

Publications

The μ-opioid receptor gene A118G polymorphism is associated with insecure attachment in children with disruptive mood regulation disorder and their mothers.

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