Epigenetic Regulation of the Kappa Opioid Receptor by Child Abuse
Open accessAbstract
Background Experiences of abuse and neglect during childhood are major predictors of the emergence of depressive and suicidal behaviors throughout life. The underlying biological mechanisms, however, remain poorly understood. Here, we focused on the opioid system as a potential brain substrate mediating these effects.Methods Postmortem samples from three brain structures regulating social bonds and emotions were analyzed. Groups were constituted of depressed individuals who died by suicide, with or without a history of severe child abuse, and of psychiatrically healthy control subjects. Expression of opioid peptides and receptors was measured using real-time polymerase chain reaction. DNA methylation, a major epigenetic mark, was investigated using targeted bisulfite sequencing and characterized at functional level using in vitro reporter assays. Finally, oxidative bisulfite sequencing was used to differentiate methylation and hydroxymethylation of DNA.Results A history of child abuse specifically associated in the anterior insula with a downregulation of the kappa opioid receptor (Kappa), as well as decreased DNA methylation in the second intron of the Kappa gene. In vitro assays further showed that this intron functions as a genomic enhancer where glucocorticoid receptor binding regulates Kappa expression, unraveling a new mechanism mediating the well-established interactions between endogenous opioids and stress. Finally, results showed that child abuse is associated in the Kappa intron with a selective reduction in levels of DNA hydroxymethylation, likely mediating the observed downregulation of the receptor.Conclusions Altogether, our findings uncover new facets of Kappa physiology, whereby this receptor may be epigenetically regulated by stressful experiences, in particular as a function of early social life.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Decreased methylation at the kappa-opioid receptor (KOR) in the anterior insula has been shown in child abuse.
“While methylation at the mu-opioid receptor (MOR) gene is most strongly associated with drug addiction [144] as well as incentive motivation for processed food [145,146], decreased methylation at the kappa-opioid receptor (KOR) in the anterior insula has been shown in child abuse [147] (discussed further in Section 4.1).”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [147]
In a study of postmortem brain structures, investigators were unable to detect a change in MOR expression, suggesting different epigenetic signatures associated with addictions and ELA.
“In this study of postmortem brain structures, the investigators were unable to detect a change in MOR expression, suggesting different epigenetic signatures associated with addictions and ELA.”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [147]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Pietrzak, R. H., Naganawa, M., Huang, Y. H., Corsi-Travali, S., Zheng, M., Stein, M. B., Henry, S. E., Lim, K., Ropchan, J. R., Lin, S.-F., et al. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1221 · Cited by 72 · see citing works
RetractedTrimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548 · see citing works
Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications
Krueger, F., & Andrews, S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr167 · Cited by 5,161 · see citing works
Comparing Individual Means in the Analysis of Variance
Tukey, J. W. (1949) · Biometrics · doi:10.2307/3001913 · Cited by 4,302 · see citing works
Burden and consequences of child maltreatment in high-income countries
Gilbert, R., Widom, C. S., Browne, K., Fergusson, D., Webb, E., & Janson, S. (2009) · The Lancet · doi:10.1016/s0140-6736(08)61706-7 · Cited by 3,876 · see citing works
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531 · see citing works
Green, J. G., McLaughlin, K. A., Berglund, P. A., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., & Kessler, R. C. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.186 · Cited by 2,323 · see citing works
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830 · see citing works
Psychopathology and early experience: A reappraisal of retrospective reports.
Brewin, C. R., Andrews, B., & Gotlib, I. H. (1993) · Psychological Bulletin · doi:10.1037/0033-2909.113.1.82 · Cited by 1,495 · see citing works
Annual research review: enduring neurobiological effects of childhood abuse and neglect
Teicher, M. H., & Samson, J. A. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12507 · Cited by 1,473 · see citing works
Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., Pace, T. W. W., Mercer, K. B., Mayberg, H. S., Bradley, B., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3275 · Cited by 1,447 · see citing works
Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain
Guo, J. U., Su, Y., Zhong, C., Ming, G., & Song, H. (2011) · Cell · doi:10.1016/j.cell.2011.03.022 · Cited by 1,355 · see citing works
THE DEVELOPMENT OF EMOTION REGULATION AND DYSREGULATION: A CLINICAL PERSPECTIVE
Cole, P. M., Michel, M. K., & Teti, L. O. (2008) · Monographs of the Society for Research in Child Development · doi:10.1111/j.1540-5834.1994.tb01278.x · Cited by 1,273 · see citing works
Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome
Yu, M., Hon, G. C., Szulwach, K. E., Song, C., Zhang, L., Kim, A., Li, X., Dai, Q., Shen, Y., Park, B., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.027 · Cited by 1,022 · see citing works
MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system
Mellén, M., Ayata, P., Dewell, S., Kriaucionis, S., & Heintz, N. (2012) · Cell · doi:10.1016/j.cell.2012.11.022 · Cited by 943 · see citing works
Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution
Booth, M. J., Branco, M. R., Ficz, G., Oxley, D., Krueger, F., Reik, W., & Balasubramanian, S. (2012) · Science · doi:10.1126/science.1220671 · Cited by 923 · see citing works
Turecki, G., & Meaney, M. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.11.022 · Cited by 796 · see citing works
Paradise lost: the neurobiological and clinical consequences of child abuse and neglect
Nemeroff, C. B. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.019 · Cited by 768 · see citing works
Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain
Mo, A., Mukamel, E. A., Davis, F. P., Luo, C., Henry, G. L., Picard, S., Urich, M. A., Nery, J. R., Sejnowski, T. J., Lister, R., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.018 · Cited by 739 · see citing works
Maternal care as a model for experience-dependent chromatin plasticity?
Meaney, M. J., & Szyf, M. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.07.006 · Cited by 658 · see citing works
The Dysphoric Component of Stress Is Encoded by Activation of the Dynorphin κ-Opioid System
Land, B. B., Bruchas, M. R., Lemos, J. C., Xu, M., Melief, E. J., & Chavkin, C. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4458-07.2008 · Cited by 601 · see citing works
Dumais, A., Lesage, A. D., Alda, M., Rouleau, G., Dumont, M., Chawky, N., Roy, M., Mann, J. J., Benkelfat, C., & Turecki, G. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.11.2116 · Cited by 583 · see citing works
Childhood Experience of Care and Abuse (CECA): A Retrospective Interview Measure
Bifulco, A., Brown, G. W., & Harris, T. O. (1994) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1994.tb01284.x · Cited by 579 · see citing works
The role of anterior insular cortex in social emotions
Lamm, C., & Singer, T. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0251-3 · Cited by 566 · see citing works
The alternative role of DNA methylation in splicing regulation
Lev-Maor, G., Yearim, A., & Ast, G. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.002 · Cited by 566 · see citing works
The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors
Bruchas, M. R., Land, B. B., & Chavkin, C. (2010) · Brain Research · doi:10.1016/j.brainres.2009.08.062 · Cited by 544 · see citing works
Opioid receptors: Distinct roles in mood disorders
Lutz, P.-E., & Kieffer, B. L. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.11.002 · Cited by 542 · see citing works
Dynorphin, stress, and depression
Knoll, A. T., & Carlezon, W. A. (2010) · Brain Research · doi:10.1016/j.brainres.2009.09.074 · Cited by 465 · see citing works
Deficit in Attachment Behavior in Mice Lacking the µ-Opioid Receptor Gene
Moles, A., Kieffer, B. L., & D'Amato, F. R. (2004) · Science · doi:10.1126/science.1095943 · Cited by 449 · see citing works
The role of the dynorphin–κ opioid system in the reinforcing effects of drugs of abuse
Wee, S., & Koob, G. F. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1825-8 · Cited by 398 · see citing works
The pleasures of play: pharmacological insights into social reward mechanisms
Trezza, V., Baarendse, P. J. J., & Vanderschuren, L. J. M. J. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.06.008 · Cited by 372 · see citing works
Neural mechanisms of social risk for psychiatric disorders
Meyer‐Lindenberg, A., & Tost, H. (2012) · Nature Neuroscience · doi:10.1038/nn.3083 · Cited by 342 · see citing works
(1998) · Journal of Affective Disorders · doi:10.1016/s0165-0327(98)00033-0 · Cited by 324 · see citing works
Beardsley, P. M., Howard, J. L., Shelton, K. L., & Carroll, F. I. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0167-4 · Cited by 312 · see citing works
Yovell, Y., Bar, G., Mashiah, M., Baruch, Y., Briskman, I., Asherov, J., Lotan, A., Rigbi, A., & Panksepp, J. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15040535 · Cited by 311 · see citing works
Toward a cross-species understanding of empathy
Panksepp, J., & Panksepp, J. B. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.009 · Cited by 296 · see citing works
Wen, L., Li, X., Yan, L., Tan, Y., Li, R., Zhao, Y., Wang, Y., Xie, J., Zhang, Y., Song, C., et al. (2014) · Genome biology · doi:10.1186/gb-2014-15-3-r49 · Cited by 288 · see citing works
Kelly, T. M., & Mann, J. J. (1996) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1996.tb09869.x · Cited by 272 · see citing works
Bruchas, M. R., Schindler, A. G., Shankar, H., Messinger, D. I., Miyatake, M., Land, B. B., Lemos, J. C., Hagan, C. E., Neumaier, J. F., Quintana, A., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.011 · Cited by 266 · see citing works
Way, B. M., Taylor, S. E., & Eisenberger, N. I. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812612106 · Cited by 264 · see citing works
Social Defeat Stress-Induced Behavioral Responses are Mediated by the Endogenous Kappa Opioid System
McLaughlin, J. P., Li, S., Valdez, J., Chavkin, T. A., & Chavkin, C. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300872 · Cited by 253 · see citing works
Memories of Childhood Neglect and Abuse: Corroboration in a Series of Sisters
Bifulco, A. T., Brown, G. W., Lillie, A., & Jarvis, J. (1997) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1997.tb01520.x · Cited by 251 · see citing works
Muschamp, J. W., Hollander, J. A., Thompson, J. L., Voren, G., Hassinger, L. C., Onvani, S., Kamenecka, T. M., Borgland, S. L., Kenny, P. J., & Carlezon, W. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315542111 · Cited by 250 · see citing works
DNA methylation and childhood maltreatment: From animal models to human studies
Lutz, P.-E., & Turecki, G. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.069 · Cited by 236 · see citing works
Bacterial infection remodels the DNA methylation landscape of human dendritic cellsPreprint
Pacis, A., Tailleux, L., Morin, A. M., Lambourne, J. J., MacIsaac, J. L., Yotova, V., Dumaine, A., Danckaert, A., Luca, F., Grenier, J., et al. (2015) · Genome Research · doi:10.1101/gr.192005.115 · Cited by 230 · see citing works
The Kappa Opioid Receptor: From Addiction to Depression, and Back
Lalanne, L., Ayrancı, G., Kieffer, B. L., & Lutz, P.-É. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00170 · Cited by 227 · see citing works
Response of the μ-opioid system to social rejection and acceptance
Hsu, D. T., Sanford, B. J., Meyers, K. K., Love, T. M., Hazlett, K. E., Wang, H., Ni, L., Walker, S. J., Mickey, B. J., Korycinski, S. T., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.96 · Cited by 225 · see citing works
Rodent empathy and affective neuroscience
Panksepp, J. B., & Lahvis, G. P. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.05.013 · Cited by 224 · see citing works
Hsu, D. T., Sanford, B. J., Meyers, K. K., Love, T. M., Hazlett, K. E., Walker, S. J., Mickey, B. J., Koeppe, R. A., Langenecker, S. A., & Zubieta, J.-K. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.185 · Cited by 205 · see citing works
Ploj, K., Roman, E., & Nylander, I. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00499-8 · Cited by 192 · see citing works
Barr, C. S., Schwandt, M. L., Lindell, S. G., Higley, J. D., Maestripieri, D., Goldman, D., Suomi, S. J., & Heilig, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710225105 · Cited by 191 · see citing works
Role of Tet1 and 5-hydroxymethylcytosine in cocaine action
Feng, J., Shao, N., Szulwach, K. E., Vialou, V., Huynh, J. L., Zhong, C., Le, T. T., Ferguson, D., Cahill, M. E., Li, Y., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3976 · Cited by 175 · see citing works
Evaluation of Opioid Modulation in Major Depressive Disorder
Ehrich, E., Turncliff, R., Du, Y., Leigh-Pemberton, R., Fernandez, E., Jones, R., & Fava, M. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.330 · Cited by 169 · see citing works
Masser, D. R., Berg, A. S., & Freeman, W. M. (2013) · Epigenetics & Chromatin · doi:10.1186/1756-8935-6-33 · Cited by 142 · see citing works
Karkhanis, A. N., Rose, J. H., Weiner, J. L., & Jones, S. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.21 · Cited by 131 · see citing works
Antidepressant-like Effects of Buprenorphine are Mediated by Kappa Opioid Receptors
Falcon, E., Browne, C. A., Leon, R. M., Fleites, V. C., Sweeney, R., Kirby, L. G., & Lucki, I. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.38 · Cited by 118 · see citing works
Conner, K. R., Conwell, Y., & Duberstein, P. R. (2001) · Acta Psychiatrica Scandinavica · doi:10.1034/j.1600-0447.2001.00091.x · Cited by 115 · see citing works
κ-Opioid Receptors within the Nucleus Accumbens Shell Mediate Pair Bond Maintenance
Resendez, S. L., Kuhnmuench, M., Krzywosinski, T., & Aragona, B. J. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5779-11.2012 · Cited by 110 · see citing works
McGirr, A., Tousignant, M., Routhier, D., Pouliot, L., Chawky, N., Margolese, H. C., & Turecki, G. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.02.025 · Cited by 110 · see citing works
Opioids and social bonding: naltrexone reduces feelings of social connection
Inagaki, T. K., Ray, L. A., Irwin, M. R., Way, B. M., & Eisenberger, N. I. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw006 · Cited by 105 · see citing works
Brent, D. A., Perper, J. A., Moritz, G., Allman, C. J., Roth, C., SCHWEERS, J., & BALACH, L. (1993) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1993.tb03341.x · Cited by 102 · see citing works
Heller, A. S., & Casey, B. J. (2015) · Developmental Science · doi:10.1111/desc.12373 · Cited by 91 · see citing works
Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice
Falcón, E., Maier, K. L., Robinson, S. A., Hill‐Smith, T. E., & Lucki, I. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3723-y · Cited by 85 · see citing works
Social ties and health: a social neuroscience perspective
Eisenberger, N. I. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.006 · Cited by 73 · see citing works
Transcriptional and Epigenetic Regulation of Opioid Receptor Genes: Present and Future
Wei, L., & Loh, H. H. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010510-100605 · Cited by 73 · see citing works
Higham, J. P., Barr, C. S., Hoffman, C. L., Mandalaywala, T. M., Parker, K. J., & Maestripieri, D. (2011) · Behavioral Neuroscience · doi:10.1037/a0022695 · Cited by 69 · see citing works
Opiate and cocaine addiction: from bench to clinic and back to the bench
Kreek, M. J., Zhou, Y., Butelman, E. R., & Levran, O. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2008.12.016 · Cited by 68 · see citing works
Polter, A. M., Bishop, R. A., Briand, L. A., Graziane, N., Pierce, R. C., & Kauer, J. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.04.019 · Cited by 64 · see citing works
Aversive motivation and the maintenance of monogamous pair bonding
Resendez, S. L., & Aragona, B. J. (2013) · Reviews in the Neurosciences · doi:10.1515/revneuro-2012-0068 · Cited by 57 · see citing works
Child μ-Opioid Receptor Gene Variant Influences Parent–Child Relations
Copeland, W., Sun, H., Costello, E. J., Angold, A. C., Heilig, M. A., & Barr, C. S. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.251 · Cited by 50 · see citing works
Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution
Gross, J. A., Pacis, A., Chen, G. G., Barreiro, L. B., Ernst, C., & Turecki, G. (2015) · BMC Genomics · doi:10.1186/s12864-015-1875-8 · Cited by 44 · see citing works
Social influences on morphine-conditioned place preference in adolescent BALB/cJ and C57BL/6J mice
Kennedy, B. C., Panksepp, J. B., Runckel, P. A., & Lahvis, G. P. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2421-2 · Cited by 42 · see citing works
Briand, L. A., Hilário, M. R. F., Dow, H. C., Brodkin, E. S., Blendy, J. A., & Berton, O. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4685-14.2015 · Cited by 42 · see citing works
Ploj, K., & Nylander, I. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00515-9 · Cited by 41 · see citing works
Chen, G. G., Gross, J. A., Lutz, P.-É., Vaillancourt, K., Maussion, G., Bramoullé, A., Théroux, J., Gardini, E., Ehlert, U., Bourret, G., et al. (2017) · BMC Genomics · doi:10.1186/s12864-017-3489-9 · Cited by 36 · see citing works
Social influences on morphine conditioned place preference in adolescent mice
Cole, S. L., Hofford, R. S., Evert, D. J., Wellman, P. J., & Eitan, S. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2011.00426.x · Cited by 32 · see citing works
Stress-induced epigenetic regulation of κ-opioid receptor gene involves transcription factor c-Myc
Flaisher-Grinberg, S., Persaud, S. D., Loh, H. H., & Wei, L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205565109 · Cited by 31 · see citing works
Huang, P., Tunis, J., Parry, C., Tallarida, R. J., & Liu‐Chen, L. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.03.061 · Cited by 29 · see citing works
Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides
Lutz, P.-É., Zhou, Y., Labbe, A., Mechawar, N., & Turecki, G. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.08.015 · Cited by 25 · see citing works
Opioid receptor blocker shows promise in Phase II depression trial
Harrison, C. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4028 · Cited by 15 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Hawton K, Appleby L, Platt S, Foster T, Cooper J, Malmberg A, et al. (1998): The psychological autopsy approach to studying suicide: a review of methodological issues. J Affect Disord. 50:269-276.
- Mai JK, Paxinos G, Voss T (2007): Atlas of the Human Brain, Third Edition. Elsevier Science.
- M'Boutchou M-N, van Kempen L (2016): Analysis of the Tumor Microenvironment Transcriptome Via NanoString mRNA and miRNA Expression Profiling. The Tumor Microenvironment: Methods and Protocols (Methods in Molecular Biology). Humana Press; 1st ed. .
- Lutz PE, Tanti A, Gasecka A, Barnett-Burns S, Kim JJ, Zhou Y, et al. (In press): Convergent epigenetic, transcriptional and morphological evidence associate a history of child abuse with impaired myelination in the anterior cingulate cortex. Am J Psychiatry.
- Turecki G, Meaney MJ (2014): Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review. Biol Psychiatry.
Cited by
Sorted by citations
The Opioid Crisis and the Future of Addiction and Pain Therapeutics
Coussens, N. P., Sittampalam, G. S., Jonson, S. G., Hall, M. D., Gorby, H. E., Tamiz, A. P., McManus, O. B., Felder, C. C., & Rasmussen, K. (2019) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.259408 · Cited by 107 · see citing works
Targeting opioid dysregulation in depression for the development of novel therapeutics
Browne, C. A., & Lucki, I. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.04.009 · Cited by 97 · see citing works
Epigenetics of childhood trauma: Long term sequelae and potential for treatment
Thumfart, K. M., Jawaid, A., Bright, K., Flachsmann, M., & Mansuy, I. M. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.10.042 · Cited by 78 · see citing works
Numan, M. (2020) · doi:10.1093/oso/9780190848675.001.0001 · Cited by 101 · see citing works
Kappa Opioid Receptor Antagonists as Potential Therapeutics for Stress-Related Disorders
Jacobson, M. L., Browne, C. A., & Lucki, I. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023317 · Cited by 70 · see citing works
Wiss, D. A., Avena, N., & Gold, M. (2020) · Nutrients · doi:10.3390/nu12113521 · Cited by 66 · see citing works
Emery, M. A., & Akil, H. (2020) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-110719-095912 · Cited by 56 · see citing works
Does Gender Leave an Epigenetic Imprint on the Brain?
Cortes, L. R., Cisternas, C. D., & Forger, N. G. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00173 · Cited by 52 · see citing works
The opioid system and the social brain: implications for depression and suicide
Lutz, P., Courtet, P., & Calati, R. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24269 · Cited by 53 · see citing works
Biological correlates of early life stressful events in major depressive disorder
Silva, R. C., Maffioletti, E., Gennarelli, M., Baune, B. T., & Minelli, A. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.105103 · Cited by 53 · see citing works
Epigenomic mediation after adverse childhood experiences: a systematic review and meta-analysis
Neves, I., Dinis‐Oliveira, R. J., & Magalhães, T. (2019) · Forensic Sciences Research · doi:10.1080/20961790.2019.1641954 · Cited by 51 · see citing works
Suicide Has Many Faces, So Does Ketamine: a Narrative Review on Ketamine’s Antisuicidal Actions
Lengvenytė, A., Olié, É., & Courtet, P. (2019) · Current Psychiatry Reports · doi:10.1007/s11920-019-1108-y · Cited by 40 · see citing works
Brown, A., Fiori, L. M., & Turecki, G. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00229 · Cited by 39 · see citing works
Novel Targets to Treat Depression: Opioid-Based Therapeutics
Browne, C. A., Jacobson, M. L., & Lucki, I. (2020) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000242 · Cited by 39 · see citing works
Matuskey, D., Dias, M., Naganawa, M., Pittman, B. P., Henry, S. E., Li, S., Gao, H., Ropchan, J. R., Nabulsi, N., Carson, R. E., et al. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0379-7 · Cited by 38 · see citing works
Nakamoto, K., & Tokuyama, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411713 · Cited by 38 · see citing works
Hao, G., Youssef, N. A., Davis, C. L., & Su, S. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.12.063 · Cited by 36 · see citing works
The Epigenetics of Early Life Adversity: Current Limitations and Possible Solutions
Barnett-Burns, S., Almeida, D. M., & Turecki, G. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.01.008 · Cited by 34 · see citing works
Kandaswamy, R., Hannon, E., Arseneault, L., Mansell, G., Sugden, K., Williams, B., Burrage, J., Staley, J. R., Pishva, E., Dahir, A., et al. (2021) · Epigenetics · doi:10.1080/15592294.2020.1853317 · Cited by 36 · see citing works
Limoges, A., Yarur, H. E., & Tejeda, H. A. (2022) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2022.963691 · Cited by 33 · see citing works
Early life stress dysregulates kappa opioid receptor signaling within the lateral habenula
Simmons, S. C., Shepard, R. D., Gouty, S., Langlois, L. D., Flerlage, W. J., Cox, B. M., & Nugent, F. S. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100267 · Cited by 32 · see citing works
Molecular impacts of childhood abuse on the human brain
Ibrahim, P., Almeida, D. M., Nagy, C., & Turecki, G. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100343 · Cited by 33 · see citing works
Gerra, M. L., Gerra, M. C., Tadonio, L., Pellegrini, P., Marchesi, C., Mattfeld, E., Gerra, G., & Ossola, P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.052 · Cited by 31 · see citing works
Epigenetic Mechanisms Activated by Childhood Adversity
Krause, B. J., Artigas, R., Sciolla, A., & Hamilton, J. (2020) · Epigenomics · doi:10.2217/epi-2020-0042 · Cited by 29 · see citing works
Focusing on the Opioid System for Addiction Biomarker Discovery
Belzeaux, R., Lalanne, L., Kieffer, B. L., & Lutz, P.-E. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.12.004 · Cited by 28 · see citing works
Almeida, D. M., Fiori, L. M., Chen, G. G., Aouabed, Z., Lutz, P.-É., Zhang, T., Mechawar, N., Meaney, M. J., & Turecki, G. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105600 · Cited by 26 · see citing works
New agents and perspectives in the pharmacological treatment of major depressive disorder
Sanches, M., Quevedo, J., & Soares, J. C. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110157 · Cited by 25 · see citing works
Lutz, P.-É., Almeida, D. M., Filliol, D., Jollant, F., Kieffer, B. L., & Turecki, G. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-00974-y · Cited by 26 · see citing works
Austin, A. E., & Shanahan, M. E. (2018) · Children and Youth Services Review · doi:10.1016/j.childyouth.2018.01.023 · Cited by 25 · see citing works
Nakamoto, K., Taniguchi, A., & Tokuyama, S. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173173 · Cited by 25 · see citing works
The Role of Opiates in Social Pain and Suicidal Behavior
Nobile, B., Lutz, P.-E., Olie, E., & Courtet, P. (2020) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2020_167 · Cited by 24 · see citing works
Opioid modulation of cognitive impairment in depression
Jacobson, M. L., Wulf, H. A., Browne, C. A., & Lucki, I. (2018) · Progress in brain research · doi:10.1016/bs.pbr.2018.07.007 · Cited by 24 · see citing works
Romero-Pimentel, A. L., Almeida, D. M., Muñoz-Montero, S. A., Rangel‐Escareño, C., Mendoza-Morales, R., González-Sáenz, E. E., Nagy, C., Chen, G., Aouabed, Z., Théroux, J., et al. (2021) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyab042 · Cited by 22 · see citing works
Johnson, B. N., McKernan, L. C., & Bruehl, S. P. (2022) · Current Pain and Headache Reports · doi:10.1007/s11916-022-01043-9 · Cited by 25 · see citing works
Endogenous Opiates and Behavior: 2018
Bodnar, R. J. (2020) · Peptides · doi:10.1016/j.peptides.2020.170348 · Cited by 22 · see citing works
Adžić, M., Lukić, I., Mitić, M., Glavonic, E., Dragicevic-Curic, N., & Ivković, S. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121803 · Cited by 21 · see citing works
Hicks, E. M., Seah, C., Cote, A. C., Marchese, S., Brennand, K., Nestler, E. J., Girgenti, M. J., & Huckins, L. M. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02412-7 · Cited by 20 · see citing works
Yarur, H. E., Casello, S. M., Tsai, V. S., Enríquez-Traba, J., Kore, R., Wang, H., Arenivar, M. A., & Tejeda, H. A. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02226-5 · Cited by 20 · see citing works
Endogenous opiates and behavior: 2017
Bodnar, R. J. (2019) · Peptides · doi:10.1016/j.peptides.2019.170223 · Cited by 19 · see citing works
Kappa Opioid Receptors in the Pathology and Treatment of Major Depressive Disorder
Browne, C. A., Wulf, H. A., & Lucki, I. (2021) · Handbook of experimental pharmacology · doi:10.1007/164_2020_432 · Cited by 18 · see citing works
Nagamatsu, S. T., Rompala, G. R., Hurd, Y. L., Núñez-Ríos, D. L., & Montalvo‐Ortiz, J. L. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1078894 · Cited by 17 · see citing works
Binder, E. B. (2019) · Der Nervenarzt · doi:10.1007/s00115-018-0657-3 · Cited by 17 · see citing works
Mechanisms and Clinical Features of Co-Occurring Opioid and Nicotine Use
Lichenstein, S. D., Zakiniaeiz, Y., Yip, S. W., & Garrison, K. A. (2019) · Current Addiction Reports · doi:10.1007/s40429-019-00245-3 · Cited by 16 · see citing works
Epigenetics in psychiatry: Beyond DNA methylation
Kouter, K., Arčan, I. Š., & Paska, A. V. (2023) · World Journal of Psychiatry · doi:10.5498/wjp.v13.i6.319 · Cited by 15 · see citing works
Biomarkers of stress resilience: A review
Paribello, P., Branchi, I., Viglione, A., Mancini, G. F., Morena, M., Campolongo, P., & Manchia, M. (2024) · Neuroscience Applied · doi:10.1016/j.nsa.2024.104052 · Cited by 16 · see citing works
Soares, J. A. G., Sutley-Koury, S. N., Pomrenze, M. B., & Tucciarone, J. (2025) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2024.1521016 · Cited by 13 · see citing works
BDNF methylation and mRNA expression in brain and blood of completed suicides in Slovenia
Ropret, S., Kouter, K., Zupanc, T., & Paska, A. V. (2021) · World Journal of Psychiatry · doi:10.5498/wjp.v11.i12.1301 · Cited by 11 · see citing works
Yuferov, V. P., Butelman, E. R., Randesi, M., Ott, J., & Kreek, M. J. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.136364 · Cited by 10 · see citing works
Gescher, D. M., Schanze, D., Vavra, P., Wolff, P., Zimmer‐Bensch, G., Zenker, M., Frodl, T., & Schmahl, C. G. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02628-z · Cited by 10 · see citing works
Opioid receptor signaling throughout ontogeny: Shaping neural and behavioral trajectories
Spodnick, M. B., McElderry, S. C., & Diaz, M. R. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106033 · Cited by 11 · see citing works
The Role of Epigenetic Dysregulation in Suicidal Behaviors
Fiori, L. M., & Turecki, G. (2020) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_160 · Cited by 9 · see citing works
Varastehmoradi, B., Smith, K. L., Müller, H. K., Elfving, B., Sánchez, C., & Wegener, G. (2023) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2023.03.010 · Cited by 8 · see citing works
Transistor chaining and transistor reordering in the design of CMOS complex gates
Carlson, B. S. (1992) · Cited by 8 · see citing works
Alkol/Madde Kullanım Bozukluklarında Şiddet ve İntiharın Nörobiyolojik Temelleri
Geniş, B., SAHİN, F., & Gürhan, N. (2022) · Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry · doi:10.18863/pgy.998217 · Cited by 7 · see citing works
Lloyd, S., Larivée, A., & Lutz, P.-É. (2022) · History & Philosophy of the Life Sciences · doi:10.1007/s40656-022-00542-7 · Cited by 7 · see citing works
Smart, K. A., Yttredahl, A. A., Oquendo, M. A., Mann, J. J., Hillmer, A. T., Carson, R. E., & Miller, J. M. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01729-5 · Cited by 6 · see citing works
Vulnerability as determinant of suicide among older people in Northern Indian states
Patel, A. B. (2022) · Frontiers in Psychology · doi:10.3389/fpsyg.2022.971080 · Cited by 6 · see citing works
Hughes, E. M., Thornton, A. M., Kerr, D. M., Smith, K. L., Sánchez, C., Kelly, J. P., Finn, D. P., & Roche, M. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.07.055 · Cited by 6 · see citing works
Allen, M. C., Moog, N. K., Buß, C., Yen, E., Gustafsson, H., Sullivan, E. L., & Graham, A. M. (2021) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2021.107033 · Cited by 7 · see citing works
Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?
Więdłocha, M., Marcinowicz, P., Komarnicki, J., Tobiaszewska, M., Dębowska, W., Dębowska, M. D., & Szulc, A. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1398859 · Cited by 6 · see citing works
Horovitz, O., Ardi, Z., Ashkenazi, S. K., Ritov, G., Anunu, R., & Richter‐Levin, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155422 · Cited by 4 · see citing works
Pursuing the elusive biosignature for suicide: a decennial update
Barzilay, R., Sudol, K., Daskalakis, N. P., Dupont, M. B., & Oquendo, M. A. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03507-5 · Cited by 3 · see citing works
Özkan-Kotiloğlu, S., Kaya-Akyüzlü, D., Şahiner, Ş. Y., & Naycı, N. A. (2023) · Pharmacogenomics · doi:10.2217/pgs-2023-0037 · Cited by 2 · see citing works
Association Between Opioid Analgesics and Suicide Attempts: A Nationwide French Case-Crossover Study
Nobile, B., Nogué, E., Picot, M., Courtet, P., Chenaf, C., Authier, N., & Olié, É. (2025) · CNS Drugs · doi:10.1007/s40263-025-01221-4 · Cited by 2 · see citing works
Epigenetics of Suicidal Behaviour
Turecki, G. (2015) · Advances in biological psychiatry · doi:10.1159/000434738 · Cited by 2 · see citing works
Pergolizzi, J. V., LeQuang, J. A., Coluzzi, F., Mariano, D. J., Nicolaou, A., & Gharibo, C. G. (2021) · doi:10.1093/med/9780198821328.003.0040 · Cited by 2 · see citing works
The epigenetics of suicide: The critical impact of environment on epigenetic regulation in suicide
Lutz, P.-É., Turecki, G., & Labonté, B. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823577-5.00010-6 · Cited by 2 · see citing works
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0008 · Cited by 2 · see citing works
Hormonal Control of Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0003 · Cited by 2 · see citing works
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0002 · Cited by 1 · see citing works
Wiss, D. A., & Logan, A. C. (2026) · Journal of Eating Disorders · doi:10.1186/s40337-026-01618-6 · Cited by 1 · see citing works
Stress-Mediated Regulation of the DNA Methylome
Dick, A. L. W., & Chen, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813156-5.00004-2 · Cited by 1 · see citing works
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0001 · Cited by 1 · see citing works
Central Neural Circuits Regulating Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0005 · Cited by 1 · see citing works
Alloparental Behavior and Paternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0007 · Cited by 1 · see citing works
Painful marks of childhood abuse
Michopoulos, V. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aao4207
Understanding the Enduring Effects of Early Abuse
Dubovsky, S. L. (2017) · Journal watch · doi:10.1056/nejm-jw.na44770
The Opioid System as a Long-Lasting Molecular Witness of Child Abuse in the Brain
Labonté, B. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.09.002
Evolutionary Perspectives on the Parental Brain
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0011
Anxiety Reduction and Maternal Aggression in Postpartum Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0006
Development of the Parental Brain in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0009
Development of the Parental Brain in Humans
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0010
Brain Mechanisms Regulating Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0004
Epigenetic Approaches to Behavioral Neuroscience
Lee, R. S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819641-0.00097-9
Epigenetics of suicidal behaviors
Fiori, L. M., & Turecki, G. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814297-4.00014-5
Parmeggiani, A., & Lanzarini, E. (2019) · Springer eBooks · doi:10.1007/978-3-030-15038-9_15
Sociobehavioral-induced epigenetic variation and psychiatric diseases
Petroff, R., Goodrich, J. M., Bakulski, K. M., & Dolinoy, D. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824010-6.00032-0
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0006
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0003
Abbreviations Used for Major Brain Regions
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0007
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0004
Escelsior, A., Guglielmo, R., Zizzi, A., Fioravanti, M., Sanvi, J., Arduino, G., Servetti, M., Colaci, F., da Silva, B. P., Nozza, P., et al. (2024) · International Journal of Mental Health and Addiction · doi:10.1007/s11469-024-01419-5
Epigenetics of Suicide: Where Are We Now?
Nobile, B., & Courtet, P. (2025) · Springer eBooks · doi:10.1007/978-981-96-1403-5_19
Costa, G. P. A., Ra, J., Meyerovich, J., Pittman, B. P., Nunes, J. C., & Aquino, J. P. D. (2025) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000001553
Weiss, E. R., Bartlett, E. A., Naganawa, M., Asch, R., Hart-Derrick, V. R., Miller, R. C., Freeman, D., Duraney, E. J., Nabulsi, N., Radhakrishnan, R., et al. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.06.017
Système opioïde et cerveau social : implication dans la dépression et le suicide
Lalanne, L., & Lutz, P.-É. (2025) · Elsevier eBooks · doi:10.1016/b978-2-294-78794-2.00013-0
- Authors
- Lutz, P.-E., Gross, J. A., Dhir, S. K., Maussion, G., Yang, J., Bramoulle, A., Meaney, M. J., & Turecki, G.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Turecki, Gustavo
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 84
- Issue
- 10
- Pages
- 751-761
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2741288947
- Cited by
- 96
- References
- 80
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 5 · 2021: 14 · 2020: 33 · 2019: 11 · 2018: 6 · 2017: 3 · 2015: 1
- FWCI
- 17.98
- Type
- journal article
- Language
- en
- Open access
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- HAL (submittedVersion)
- Funders
- Fondation Bettencourt Schueller
- Canadian Institutes of Health Research
- Fondation pour la Recherche Médicale
- American Foundation for Suicide Prevention
- Fondation Fyssen
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- kappa opioid receptor, child abuse, epigenetic regulation, DNA methylation, DNA hydroxymethylation, glucocorticoid receptor, anterior insula, depression, suicide, opioid system, early life stress, gene downregulation
- MeSH terms
- Adult, Cerebral Cortex, Child, Child Abuse, Depressive Disorder, Female, Humans, Male, Middle Aged, Promoter Regions, Genetic, Suicide, Thalamus, Receptors, Opioid, kappa, DNA Methylation, Epigenesis, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
