Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence of suicidal ideation at antidepressant onset in a large naturalistic cohort of depressed outpatients

Nobile, Bénédicte; Ramoz, Nicolás; Jaussent, Isabelle; Gorwood, Philip; Olié, Émilie; Castroman, J. Lopez; Guillaume, Sébastien; Courtet, P.

doi:10.1038/s41598-019-39622-3

Cited by 29 publications

(21 citation statements)

References 62 publications

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“…SPAG17 (sperm-associated antigen 17) was previously identified by whole exome sequencing of suicide deaths as a locus enriched for rare variants ( Tombacz et al, 2017 ). OPRM1 encodes the mu-opioid receptor 1 and has garnered considerable attention in candidate gene and large-scale genetic studies of several psychiatric disorders and suicidal ideation ( Nobile et al, 2019 ) and suicidal behavior ( Arias et al, 2012 ). We also detected inhibitory neurons from layers 2–5 of the middle temporal gyrus expressing both SCUBE3 and PVALB .…”

Section: Discussionmentioning

confidence: 99%

Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality

Wendt

Pathak

Levey

et al. 2021

Neurobiology of Stress

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Epidemiologic studies recognize that trauma and posttraumatic stress are associated with heightened suicidal behavior severity, yet examination of these associations from a genetic perspective is limited. We performed a multivariate gene-by-environment genome-wide interaction study (GEWIS) of suicidality in 123,633 individuals using a covariance matrix based on 26 environments related to traumatic experiences, posttraumatic stress, social support, and socioeconomic status. We discovered five suicidality risk loci, including the male-associated rs2367967 ( CWC22 ), which replicated in an independent cohort. All GEWIS-significant loci exhibited interaction effects where at least 5% of the sample had environmental profiles conferring opposite SNP effects from the majority. We identified PTSD as a primary driving environment for GxE at suicidality risk loci. The male suicidality GEWIS was enriched for three middle-temporal-gyrus inhibitory neuron transcriptomic profiles: SCUBE - and PVALB -expressing cells ( β = 0.028, p = 3.74 × 10 −4 ), OPRM1 -expressing cells ( β = 0.030, p = 0.001), and SPAG17 -expressing cells ( β = 0.029, p = 9.80 × 10 −4 ). Combined with gene-based analyses ( CNTN5 p association = 2.38 × 10 −9 , p interaction = 1.51 × 10 −3 ; PSMD14 p association = 2.04 × 10 −7 , p interaction = 7.76 × 10 −6 ; HEPACAM p association = 2.43 × 10 −6 , p interaction = 3.82 × 10 −7 ) including information about brain chromatin interaction profiles ( UBE2E3 in male neuron p = 1.07 × 10 −5 ), our GEWIS points to extracellular matrix biology and synaptic plasticity as biological interactors with the effects of potentially modifiable lifetime traumatic experiences on genetic risk for suicidality. Characterization of molecular basis for the effects of traumatic experience and posttraumatic stress on risk of suicidal behaviors may help to identify novel targets for which more effective treatments can be developed for use in high-risk populations.

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Section: Discussionmentioning

confidence: 99%

Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality

Wendt

Pathak

Levey

et al. 2021

Neurobiology of Stress

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“…A previous study showed that a single suicide item from a depression rating scale is a valid approach to assess SI compared with the Scale for Suicide Ideation (Desseilles et al, 2012). This method was previously used in large clinical studies, such as the STAR*D (Zisook et al, 2009), and also in more recent studies (Bernert et al, 2017; Nobile et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

Characterization of depressed bipolar patients with current suicidal ideation

Nobile

Dubois

Aouizerate

et al. 2020

Aust N Z J Psychiatry

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Objective: Bipolar disorder is one of the most frequent psychiatric disorders among suicidal patients. A large part of patients with bipolar disorder (30–50%) will attempt suicide. Suicidal ideation being a major risk factor of suicidal act, it is crucial to better characterize patients with suicidal bipolar depression (i.e. depression with current suicidal ideation). The aim of this study was to characterize suicidal bipolar depressed patients in comparison with non-suicidal depressed patients in terms of clinical characteristics, evolution of depression and suicidal ideation course over time, and risk of suicide attempt during follow-up. Methods: Among patients with bipolar disorder recruited from the network of FondaMental expert centres for bipolar disorder between 2009 and 2017, we selected patients with at least mild depression (Montgomery–Åsberg Depression Rating Scale total score >11) and without current manic symptomatology (Young Mania Rating Scale total score <7) at baseline ( N = 938). Suicidal depression was defined by a baseline score ⩾2 for item 12 of the Quick Inventory of Depressive Symptomatology–Self Report ( N = 271, 28.9%). Non-suicidal depression was defined by a baseline item 12 of the Quick Inventory of Depressive Symptomatology–Self Report score <2 ( N = 667, 71.1%). A subsample of about 300 patients (with or without suicidal ideation at baseline) was followed up for 2 years. Results: Baseline clinical features (e.g. depression severity, childhood trauma, global functioning) were more severe in patients with than without suicidal depression. Suicidal patients tended to remain more suicidal throughout the follow-up than patients without suicidal ideation at baseline (3.4-fold higher risk of persistent suicidal ideation at the 2-year visit despite an improvement in depressive symptomatology). Conclusions: Depressed bipolar disorder patients reporting suicidal ideation had more severe clinical features at baseline and were more prone to report persistent suicidal ideation during the follow-up, independently of thymic state. Clinicians should closely monitor this subgroup of patients.

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“…Recently, a role has been recognized for the A118G SNP in mediating affiliative behavior, such as affectionate relationships and attachment (Nobile et al., 2019; Troisi et al., 2011). Importantly, it has been shown that this SNP is involved in social attachment and the social reward system in children (Copeland et al., 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Although the research in this field has focused on the A118G polymorphism and on several psychopathological traits, such as stress response, social anhedonia (Lovallo et al., 2015; Troisi et al., 2011), and heightened sensitivity to social rejection (Way et al., 2009), and on psychopathologies such as addictive behaviors, depression, and suicide (Kennedy et al., 2006; Nobile et al., 2019; Schwantes‐An et al., 2016), no studies have confirmed its association with the disruptive mood dysregulation disorder (DMDD) in school‐age youths. This clinical condition has a prevalence of 2%–5% in pediatric psychiatric populations, and it has been recently included among the depressive disorders in DSM‐5 (American Psychiatric Association, 2013), being characterized by a severe impairment in the emotion and behavioral regulatory processes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Background 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 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 μ‐opioid receptor gene and emotional/behavioral functioning, attachment style in children, and psychopathology and caregiving ability in mothers.

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Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence of suicidal ideation at antidepressant onset in a large naturalistic cohort of depressed outpatients

Cited by 29 publications

References 62 publications

Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality

Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality

Characterization of depressed bipolar patients with current suicidal ideation

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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