Cannabinoid receptor genotype moderation of the effects of childhood physical abuse on anhedonia and depression.
- Authors
- Agrawal, Arpana; Nelson, Elliot C; Littlefield, Andrew K; Bucholz, Kathleen K; Degenhardt, Louisa; Henders, Anjali K; Madden, Pamela A F; Martin, Nicholas G; Montgomery, Grant W; Pergadia, Michele L; Sher, Kenneth J; Heath, Andrew C; Lynskey, Michael T
- Year
- 2012
- Journal
- Archives of general psychiatry
- PMID
- 22393204
- DOI
- 10.1001/archgenpsychiatry.2011.2273
- PMCID
- PMC3706194
CONTEXT: The endocannabinoid system has been implicated in stress adaptation and the regulation of mood in rodent studies, but few human association studies have examined these links and replications are limited. OBJECTIVES: To examine whether a synonymous polymorphism, rs1049353, in exon 4 of the gene encoding the human endocannabinoid receptor (CNR1) moderates the effect of self-reported childhood physical abuse on lifetime anhedonia and depression and to replicate this interaction in an independent sample. DESIGN, SETTING, AND PARTICIPANTS: Genetic association study in 1041 young US women with replication in an independent Australian sample of 1428 heroin-dependent individuals as cases and 506 participants as neighborhood controls. MAIN OUTCOME MEASURES: Self-reported anhedonia and depression (with anhedonia). RESULTS: In both samples, individuals who experienced childhood physical abuse were considerably more likely to report lifetime anhedonia. However, in those with 1 or more copies of the minor allele of rs1049353, this pathogenic effect of childhood physical abuse was attenuated. Thus, in participants reporting childhood physical abuse, although 57.1% of those homozygous for the major allele reported anhedonia, only 28.6% of those who were carriers of the minor allele reported it (P=.01). The rs1049353 polymorphism also buffered the effects of childhood physical abuse on major depressive disorder; however, this influence was largely attributable to anhedonic depression. These effects were also noted in an independent sample, in which minor allele carriers were at decreased risk for anhedonia even when exposed to physical abuse. CONCLUSIONS: Consistent with preclinical findings, a synonymous CNR1 polymorphism, rs1049353, is linked to the effects of stress attributable to childhood physical abuse on anhedonia and anhedonic depression. This polymorphism reportedly resides in the neighborhood of an exon splice enhancer; hence, future studies should carefully examine its effect on expression and conformational variation in CNR1, particularly in relation to stress adaptation.
Interaction between rs1049353 (CNR1) and childhood physical abuse and its association with anehdonia in two independent samplesThe association between childhood physical abuse and anhedonia as a function of rs1049353. Dark red lines represent exposure to childhood physical abuse, dashed blue lines represent no exposure to physical abuse. The dotted green line in the replication sample represents intermediate exposure to abuse whereas the solid red line is high exposure and the dashed blue line is low exposure. Numbers are color-coded to represent the total (black) as well as those with each type of genotype, stratified by childhood physical abuse.
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Defining anhedonia subgroups using the dimensional anhedonia rating scale in active depression: Findings from the Texas resilience against depression study. | Chin Fatt CR et al. | — | 2026 | → |
| Quantitative scale validation of the Dimensional Anhedonia Rating Scale in the treatment of Chinese patients with major depressive disorder. | Gu X et al. | — | 2025 | → |
| G protein-coupled receptor (GPCR) pharmacogenomics. | Thompson MD et al. | — | 2024 | → |
| The role of anhedonia in the relationship between adverse childhood experiences (ACEs), alcohol use disorder symptoms, and food addiction symptoms in a sample of emerging adults with histories of heavy drinking. | Takgbajouah M et al. | — | 2024 | → |
| Childhood Neglect rather than Abuse Is More Strongly Associated with Anhedonia across Major Depression and Obsessive-Compulsive Disorder Patients and University Students. | Fan J et al. | — | 2023 | → |
| The Differential Relation of Emotional, Physical, and Sexual Abuse Histories to Antidepressant Treatment Remission and Persistence of Anhedonia in Major Depression: A CAN-BIND-1 Report. | Harkness KL et al. | — | 2023 | → |
| Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence. | Kuhns L et al. | — | 2022 | → |
| Circulating endocannabinoids and genetic polymorphisms as predictors of posttraumatic stress disorder symptom severity: heterogeneity in a community-based cohort. | deRoon-Cassini TA et al. | — | 2022 | → |
| Dysfunctional Attitudes Mediate the Relationship Between Childhood Emotional Neglect and Anhedonia in Young Adult Major Depression Patients. | Wang P et al. | — | 2022 | → |
| Associations Among Parental Caregiving Quality, Cannabinoid Receptor 1 Expression-Based Polygenic Scores, and Infant-Parent Attachment: Evidence for Differential Genetic Susceptibility? | Potter-Dickey A et al. | — | 2021 | → |
| Childhood trauma is associated with elevated anhedonia and altered core reward circuitry in major depression patients and controls. | Fan J et al. | — | 2021 | → |
| Circulating endocannabinoids and prospective risk for depression in trauma-injury survivors. | Fitzgerald JM et al. | — | 2021 | → |
| Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers. | Morel A et al. | — | 2021 | → |
| On the Role of Central Type-1 Cannabinoid Receptor Gene Regulation in Food Intake and Eating Behaviors. | Pucci M et al. | — | 2021 | → |
| Preliminary Evidence for Anhedonia as a Marker of Sexual Trauma in Female Adolescents. | Sonmez AI et al. | — | 2021 | → |
| Prevalence and associated risk factors of cannabinoid abuse among Egyptian university students: a cross-sectional study. | Naguib YM et al. | — | 2021 | → |
| Preventing E-cigarette use among high-risk adolescents: A trauma-informed prevention approach. | Shin SH | — | 2021 | → |
| Resilience to fear: The role of individual factors in amygdala response to stressors. | Fonseca R et al. | — | 2021 | → |
| Variability in cannabinoid receptor genes is associated with psychiatric comorbidities in anorexia nervosa. | González LM et al. | — | 2021 | → |
| Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme. | Hindocha C et al. | — | 2020 | → |
| Cannabidiol as a Treatment for Mood Disorders: A Systematic Review. | Pinto JV et al. | — | 2020 | → |
| Endocannabinoid System Components as Potential Biomarkers in Psychiatry. | Navarrete F et al. | — | 2020 | → |
| Parenting Interacts With Plasticity Genes in Predicting Behavioral Outcomes in Preschoolers. | Letourneau NL et al. | — | 2020 | → |
| The effect of polymorphisms in startle-related genes on anxiety symptom severity. | Tomasi J et al. | — | 2020 | → |
| Composite kernel machine regression based on likelihood ratio test for joint testing of genetic and gene-environment interaction effect. | Zhao N et al. | — | 2019 | → |
| Depression as a Neuroendocrine Disorder: Emerging Neuropsychopharmacological Approaches beyond Monoamines. | Chávez-Castillo M et al. | — | 2019 | → |
| Early life stress alters the developmental trajectory of corticolimbic endocannabinoid signaling in male rats. | Hill MN et al. | — | 2019 | → |
| Effects of Different Stressors Are Modulated by Different Neurobiological Systems: The Role of GABA-A Versus CB1 Receptor Gene Variants in Anxiety and Depression. | Gonda X et al. | — | 2019 | → |
| The prevalence and clinical correlates of cannabis use and cannabis use disorder among patients with bipolar disorder: A systematic review with meta-analysis and meta-regression. | Pinto JV et al. | — | 2019 | → |
| Trends of major depressive episode among people with cannabis use: Findings from the National Survey on Drug Use and Health 2006-2015. | Carrà G et al. | — | 2019 | → |
| Adult Cellular Neuroadaptations Induced by Adolescent THC Exposure in Female Rats Are Rescued by Enhancing Anandamide Signaling. | Cuccurazzu B et al. | — | 2018 | → |
| An endocannabinoid receptor polymorphism modulates affective processing under stress. | Wirz L et al. | — | 2018 | → |
| Can Your DNA Influence Your Bet-Placing? The Impact of Cannabinoid Receptor 1 Gene on Gambling Tasks. | Qin H et al. | — | 2018 | → |
| Exploiting the Multifaceted Effects of Cannabinoids on Mood to Boost Their Therapeutic Use Against Anxiety and Depression. | Stampanoni Bassi M et al. | — | 2018 | → |
| Gene variants and educational attainment in cannabis use: mediating role of DNA methylation. | Gerra MC et al. | — | 2018 | → |
| Sex-dependent impact of early-life stress and adult immobilization in the attribution of incentive salience in rats. | Fuentes S et al. | — | 2018 | → |
| The utility of twins in developmental cognitive neuroscience research: How twins strengthen the ABCD research design. | Iacono WG et al. | — | 2018 | → |
| Cannabinoid Receptor 1 and Fatty Acid Amide Hydrolase Contribute to Operant Sensation Seeking in Mice. | Helfand AI et al. | — | 2017 | → |
| Childhood Adversities and Depression in Adulthood: Current Findings and Future Directions. | Liu RT | — | 2017 | → |
| Endocannabinoid signaling and memory dynamics: A synaptic perspective. | Drumond A et al. | — | 2017 | → |
| Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study. | Agrawal A et al. | — | 2017 | → |
| Role of Endocannabinoids on Sweet Taste Perception, Food Preference, and Obesity-related Disorders. | Tarragon E et al. | — | 2017 | → |
| Neurobiological Interactions Between Stress and the Endocannabinoid System. | Morena M et al. | — | 2016 | → |
| The variance shared across forms of childhood trauma is strongly associated with liability for psychiatric and substance use disorders. | Kristjansson S et al. | — | 2016 | → |
| A cannabinoid receptor 1 polymorphism is protective against major depressive disorder in methadone-maintained outpatients. | Icick R et al. | — | 2015 | → |
| Cannabis and adolescent brain development. | Lubman DI et al. | — | 2015 | → |
| Endocannabinoids and Mental Disorders. | Rubino T et al. | — | 2015 | → |
| High Times for Painful Blues: The Endocannabinoid System in Pain-Depression Comorbidity. | Fitzgibbon M et al. | — | 2015 | → |
| Kernel Approach for Modeling Interaction Effects in Genetic Association Studies of Complex Quantitative Traits. | Broadaway KA et al. | — | 2015 | → |
| Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis. | Carey CE et al. | — | 2015 | → |
| Reinforcement learning in depression: A review of computational research. | Chen C et al. | — | 2015 | → |
| Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents. | Buchmann AF et al. | — | 2015 | → |
| The rs1049353 polymorphism in the CNR1 gene interacts with childhood abuse to predict posttraumatic threat symptoms. | Mota N et al. | — | 2015 | → |
| Cannabis controversies: how genetics can inform the study of comorbidity. | Agrawal A et al. | — | 2014 | → |
| Endocannabinoid signaling in the etiology and treatment of major depressive illness. | Hillard CJ et al. | — | 2014 | → |
| Gene-environment interactions and intermediate phenotypes: early trauma and depression. | Hornung OP et al. | — | 2014 | → |
| Have the genetics of cannabis involvement gone to pot? | Agrawal A et al. | — | 2014 | → |
| Pharmacogenetics of the G protein-coupled receptors. | Thompson MD et al. | — | 2014 | → |
| Stress regulates endocannabinoid-CB1 receptor signaling. | Hillard CJ | — | 2014 | → |
| Towards a personalized treatment in depression: endocannabinoids, inflammation and stress response. | Zajkowska ZE et al. | — | 2014 | → |
| Anhedonia: a concept analysis. | Ho N et al. | — | 2013 | → |
| Endocannabinoid system and mood disorders: priming a target for new therapies. | Micale V et al. | — | 2013 | → |
| Gene environment interaction studies in depression and suicidal behavior: An update. | Mandelli L et al. | — | 2013 | → |
| Increased risk of major depression by childhood abuse is not modified by CNR1 genotype. | Pearson JF et al. | — | 2013 | → |
| Neurogenetics of depression: a focus on reward processing and stress sensitivity. | Bogdan R et al. | — | 2013 | → |
| Psychosocial factors and hematopoietic stem cell transplantation: potential biobehavioral pathways. | Knight JM et al. | — | 2013 | → |
| Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses. | Hill MN et al. | — | 2013 | → |