DOI QR코드

DOI QR Code

Origins of Addiction Predictably Embedded in Childhood Trauma: A Neurobiological Review

  • Wiet, Susie (General, Child and Adolescent Psychiatrist, Addiction Medicine, Holistic Treament for Psychiatry Trauma Addiction, University ot Utah-Adjunct Volunteer Faculty)
  • Received : 2016.10.02
  • Accepted : 2016.11.08
  • Published : 2017.01.01

Abstract

The seeds of addiction are typically sown years prior to the onset of addictive substance use or engagement in addictive behaviors, due to the priming of the reward pathway (RewP) by alterations in the mechanism of stress-signaling from the hypothalamic-pituitary-adrenal axis (HPA) and related pathways. Excessive stress from a single-event and/or cumulative life experiences during childhood, such as those documented in the Adverse Childhood Experiences Study, is translated into neurobiological toxicity that alters the set-point of the HPA axis and limbic system homeostasis [suggested new term: regulation pathway (RegP)]. The resultant alteration of the RegP not only increases the risk for psychiatric and physical illness, but also that for early onset and chronic addictions by dysregulating the RewP. This paper reviews the interface of these symbiotic pathways that result in the phenotypic pathology of emotional dysregulation, cognitive impairment, and compulsive behaviors, as well as morbidity and shorter life expectancy when dysregulated by chronic stress.

Keywords

References

  1. American Society of Addiction Medicine. Public policy statement: short definition of addiction. [cited 2011 Dec 4]. Available from: http://www.asam.org/quality-practice/definition-of-addiction.
  2. Sapolsky RM. Stress, glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1996;1:1-19. https://doi.org/10.3109/10253899609001092
  3. Qin D, Patel SM, Champion HC. "Happiness" and stress cardiomyopathy (apical ballooning syndrome/takotsubo syndrome). Int J Cardiol 2014;172:e182-e183. https://doi.org/10.1016/j.ijcard.2013.12.140
  4. Schleifer SJ, Macari-Hinson MM, Coyle DA, Slater WR, Kahn M, Gorlin R, et al. The nature and course of depression following myocardial infarction. Arch Intern Med 1989;149:1785-1789. https://doi.org/10.1001/archinte.1989.00390080059014
  5. Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The adverse childhood experiences (ACE) Study. Am J Prev Med 1998;14:245-258. https://doi.org/10.1016/S0749-3797(98)00017-8
  6. Dube SR, Felitti VJ, Dong M, Chapman DP, Giles WH, Anda RF. Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study. Pediatrics 2003;111:564-572. https://doi.org/10.1542/peds.111.3.564
  7. Dube SR, Felitti VJ, Dong M, Giles WH, Anda RF. The impact of adverse childhood experiences on health problems: evidence from four birth cohorts dating back to 1900. Prev Med 2003;37:268-277. https://doi.org/10.1016/S0091-7435(03)00123-3
  8. Dong M, Giles WH, Felitti VJ, Dube SR, Williams JE, Chapman DP, et al. Insights into causal pathways for ischemic heart disease: adverse childhood experiences study. Circulation 2004;110:1761-1766. https://doi.org/10.1161/01.CIR.0000143074.54995.7F
  9. Huang H, Yan P, Shan Z, Chen S, Li M, Luo C, et al. Adverse childhood experiences and risk of type 2 diabetes: a systematic review and meta-analysis. Metabolism 2015;64:1408-1418. https://doi.org/10.1016/j.metabol.2015.08.019
  10. Fuemmeler BF, Dedert E, McClernon FJ, Beckham JC. Adverse childhood events are associated with obesity and disordered eating: results from a U.S. population-based survey of young adults. J Trauma Stress 2009;22:329-333. https://doi.org/10.1002/jts.20421
  11. Brown MJ, Thacker LR, Cohen SA. Association between adverse childhood experiences and diagnosis of cancer. PLoS One 2013;8:e65524. https://doi.org/10.1371/journal.pone.0065524
  12. Chapman DP, Whitfield CL, Felitti VJ, Dube SR, Edwards VJ, Anda RF. Adverse childhood experiences and the risk of depressive disorders in adulthood. J Affect Disord 2004;82:217-225. https://doi.org/10.1016/j.jad.2003.12.013
  13. Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 2001;49:1023-1039. https://doi.org/10.1016/S0006-3223(01)01157-X
  14. Wu NS, Schairer LC, Dellor E, Grella C. Childhood trauma and health outcomes in adults with comorbid substance abuse and mental health disorders. Addict Behav 2010;35:68-71. https://doi.org/10.1016/j.addbeh.2009.09.003
  15. Dube SR, Fairweather D, Pearson WS, Felitti VJ, Anda RF, Croft JB. Cumulative childhood stress and autoimmune diseases in adults. Psychosom Med 2009;71:243-250. https://doi.org/10.1097/PSY.0b013e3181907888
  16. Friedman H, Eisenstein TK. Neurological basis of drug dependence and its effects on the immune system. J Neuroimmunol 2004;147: 106-108. https://doi.org/10.1016/j.jneuroim.2003.10.022
  17. Saper CB, Lowell BB. The hypothalamus. Curr Biol 2014;24:R1111-R1116. https://doi.org/10.1016/j.cub.2014.10.023
  18. Padilla SL, Reef D, Zeltser LM. Defining POMC neurons using transgenic reagents: impact of transient Pomc expression in diverse immature neuronal populations. Endocrinology 2012;153:1219-1231. https://doi.org/10.1210/en.2011-1665
  19. Sprouse-Blum AS, Smith G, Sugai D, Parsa FD. Understanding endorphins and their importance in pain management. Hawaii Med J 2010;69:70-71.
  20. Schafer M, Carter L, Stein C. Interleukin 1 beta and corticotropinreleasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue. Proc Natl Acad Sci U S A 1994;91:4219-4223. https://doi.org/10.1073/pnas.91.10.4219
  21. Welch CC, Kim EM, Grace MK, Billington CJ, Levine AS. Palatability-induced hyperphagia increases hypothalamic dynorphin peptide and mRNA levels. Brain Res 1996;721:126-131. https://doi.org/10.1016/0006-8993(96)00151-5
  22. Wersinger SR, Caldwell HK, Martinez L, Gold P, Hu SB, Young WS 3rd. Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression. Genes Brain Behav 2007;6:540-551. https://doi.org/10.1111/j.1601-183X.2006.00281.x
  23. Bremne JD, Vermetten E. Stress and development: behavioral and biological consequences. Dev Psychopathol 2001;13:473-489. https://doi.org/10.1017/S0954579401003042
  24. Szeto HH. Dynorphin and the hypothalamo-pituitary-adrenal axis during fetal development. Life Sci 2003;73:749-758. https://doi.org/10.1016/S0024-3205(03)00407-7
  25. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 2002;53:865-871. https://doi.org/10.1016/S0022-3999(02)00429-4
  26. Tomkins DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence. CMAJ 2001;164:817-821.
  27. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 2004;130:601-630. https://doi.org/10.1037/0033-2909.130.4.601
  28. Nestler EJ. Is there a common molecular pathway for addiction? Nat Neurosci 2005;8:1445-1449. https://doi.org/10.1038/nn1578
  29. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology 2010;35:217-238. https://doi.org/10.1038/npp.2009.110
  30. Jennings JH, Sparta DR, Stamatakis AM, Ung RL, Pleil KE, Kash TL, et al. Distinct extended amygdala circuits for divergent motivational states. Nature 2013;496:224-228. https://doi.org/10.1038/nature12041
  31. Franklin TR, Wang Z, Wang J, Sciortino N, Harper D, Li Y, et al. Limbic activation to cigarette smoking cues independent of nicotine withdrawal: a perfusion fMRI study. Neuropsychopharmacology 2007;32:2301-2309. https://doi.org/10.1038/sj.npp.1301371
  32. Kelley AE, Baldo BA, Pratt WE. A proposed hypothalamic-thalamic- striatal axis for the integration of energy balance, arousal, and food reward. J Comp Neurol 2005;493:72-85. https://doi.org/10.1002/cne.20769
  33. Ford JD, Kidd P. Early childhood trauma and disorders of extreme stress as predictors of treatment outcome with chronic posttraumatic stress disorder. J Trauma Stress 1998;11:743-761. https://doi.org/10.1023/A:1024497400891
  34. Triffleman EG, Marmar CR, Delucchi KL, Ronfeldt H. Childhood trauma and posttraumatic stress disorder in substance abuse inpatients. J Nerv Ment Dis 1995;183:172-176. https://doi.org/10.1097/00005053-199503000-00008
  35. Bremner JD, Southwick SM, Johnson DR, Yehuda R, Charney DS. Childhood physical abuse and combat-related posttraumatic stress disorder in Vietnam veterans. Am J Psychiatry 1993;150:235-239. https://doi.org/10.1176/ajp.150.2.235
  36. Saxon AJ, Davis TM, Sloan KL, McKnight KM, McFall ME, Kivlahan DR. Trauma, symptoms of posttraumatic stress disorder, and associated problems among incarcerated veterans. Psychiatr Serv 2001;52:959-964. https://doi.org/10.1176/appi.ps.52.7.959
  37. Heffernan K, Cloitre M, Tardiff K, Marzuk PM, Portera L, Leon AC. Childhood trauma as a correlate of lifetime opiate use in psychiatric patients. Addict Behav 2000;25:797-803. https://doi.org/10.1016/S0306-4603(00)00066-6
  38. Koob GF. A role for brain stress systems in addiction. Neuron 2008; 59:11-34. https://doi.org/10.1016/j.neuron.2008.06.012
  39. Ivy AS, Rex CS, Chen Y, Dube C, Maras PM, Grigoriadis DE, et al. Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors. J Neurosci 2010;30:13005-13015. https://doi.org/10.1523/JNEUROSCI.1784-10.2010
  40. Chen P, Vaughan J, Donaldson C, Vale W, Li C. Injection of urocortin 3 into the ventromedial hypothalamus modulates feeding, blood glucose levels, and hypothalamic POMC gene expression but not the HPA axis. Am J Physiol Endocrinol Metab 2010;298:E337-E345. https://doi.org/10.1152/ajpendo.00402.2009
  41. McGowan PO. Epigenomic mechanisms of early adversity and HPA dysfunction: considerations for PTSD research. Front Psychiatry 2013;4:110.
  42. Sousa N, Lukoyanov NV, Madeira MD, Almeida OF, Paula-Barbosa MM. Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience 2000;97:253-266. https://doi.org/10.1016/S0306-4522(00)00050-6
  43. Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, et al. Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 2004;47 Suppl 1:227-241. https://doi.org/10.1016/j.neuropharm.2004.06.032
  44. Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 2001;24:97-129. https://doi.org/10.1016/S0893-133X(00)00195-0
  45. Erb S, Shaham Y, Stewart J. Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period. Psychopharmacology (Berl) 1996;128:408-412. https://doi.org/10.1007/s002130050150
  46. DeSantis SM, Baker NL, Back SE, Spratt E, Ciolino JD, Moran-Santa Maria M, et al. Gender differences in the effect of early life trauma on hypothalamic-pituitary-adrenal axis functioning. Depress Anxiety 2011;28:383-392. https://doi.org/10.1002/da.20795
  47. Rousseau K, Kauser S, Pritchard LE, Warhurst A, Oliver RL, Slominski A, et al. Proopiomelanocortin (POMC), the ACTH/melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis. FASEB J 2007;21:1844-1856. https://doi.org/10.1096/fj.06-7398com
  48. Polter AM, Kauer JA. Stress and VTA synapses: implications for addiction and depression. Eur J Neurosci 2014;39:1179-1188. https://doi.org/10.1111/ejn.12490
  49. Dunbar JC, Lu H. Proopiomelanocortin (POMC) products in the central regulation of sympathetic and cardiovascular dynamics: studies on melanocortin and opioid interactions. Peptides 2000;21: 211-217. https://doi.org/10.1016/S0196-9781(99)00192-8
  50. Heinz A, Siessmeier T, Wrase J, Hermann D, Klein S, Grusser SM, et al. Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 2004;161:1783-1789. https://doi.org/10.1176/ajp.161.10.1783
  51. Berridge KC. The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology (Berl) 2007;191:391-431. https://doi.org/10.1007/s00213-006-0578-x
  52. Sanchis-Segura C, Spanagel R. Behavioural assessment of drug reinforcement and addictive features in rodents: an overview. Addict Biol 2006;11:2-38. https://doi.org/10.1111/j.1369-1600.2006.00012.x
  53. Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL. Relapse to cocaine- seeking after hippocampal theta burst stimulation. Science 2001;292:1175-1178. https://doi.org/10.1126/science.1058043
  54. Sinha R, Fuse T, Aubin LR, O'Malley SS. Psychological stress, drugrelated cues and cocaine craving. Psychopharmacology (Berl) 2000;152:140-148. https://doi.org/10.1007/s002130000499
  55. Vinson GP, Brennan CH. Addiction and the adrenal cortex. Endocr Connect 2013;2:R1-R14. https://doi.org/10.1530/EC-13-0028
  56. Niikura K, Zhou Y, Ho A, Kreek MJ. Proopiomelanocortin (POMC) expression and conditioned place aversion during protracted withdrawal from chronic intermittent escalating-dose heroin in POMCEGFP promoter transgenic mice. Neuroscience 2013;236:220-232. https://doi.org/10.1016/j.neuroscience.2012.12.071
  57. Jamero D, Borghol A, Vo N, Hawawini F. The emerging role of NMDA antagonists in pain management. US Pharm 2011;36: HS4-HS8.
  58. Marinova Z. Opioid and non-opioid activities of the dynorphins [dissertation]. Stockholm, Karolinska institutet;2006.
  59. Shah PS, Shah J; Knowledge Synthesis Group on Determinants of Preterm/LBW Births. Maternal exposure to domestic violence and pregnancy and birth outcomes: a systematic review and metaanalyses. J Womens Health (Larchmt) 2010;19:2017-2031. https://doi.org/10.1089/jwh.2010.2051
  60. Radtke KM, Ruf M, Gunter HM, Dohrmann K, Schauer M, Meyer A, et al. Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Transl Psychiatry 2011;1:e21. https://doi.org/10.1038/tp.2011.21
  61. Russo SJ, Murrough JW, Han MH, Charney DS, Nestler EJ. Neurobiology of resilience. Nat Neurosci. 2012;15:1475-1484. https://doi.org/10.1038/nn.3234
  62. Mao J. NMDA and opioid receptors: their interactions in antinociception, tolerance and neuroplasticity. Brain Res Brain Res Rev 1999;30:289-304. https://doi.org/10.1016/S0165-0173(99)00020-X
  63. Pleil KE, Rinker JA, Lowery-Gionta EG, Mazzone CM, McCall NM, Kendra AM, et al. NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nat Neurosci 2015;18:545-552. https://doi.org/10.1038/nn.3972
  64. Kakui N, Kitamura K. Direct evidence that stimulation of neuropeptide Y Y5 receptor activates hypothalamo-pituitary-adrenal axis in conscious rats via both corticotropin-releasing factor- and arginine vasopressin-dependent pathway. Endocrinology 2007;148:2854-2862. https://doi.org/10.1210/en.2007-0189
  65. Lin S, Boey D, Lee N, Schwarzer C, Sainsbury A, Herzog H. Distribution of prodynorphin mRNA and its interaction with the NPY system in the mouse brain. Neuropeptides 2006;40:115-123. https://doi.org/10.1016/j.npep.2005.11.006
  66. Ganella DE, Ma S, Gundlach AL. Relaxin-3/RXFP3 signaling and neuroendocrine function - a perspective on extrinsic hypothalamic control. Front Endocrinol (Lausanne) 2013;4:128.
  67. Seidenbecher T, Laxmi TR, Stork O, Pape HC. Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval. Science 2003;301:846-850. https://doi.org/10.1126/science.1085818
  68. Ryan PJ, Ma S, Olucha-Bordonau FE, Gundlach AL. Nucleus incertus--an emerging modulatory role in arousal, stress and memory. Neurosci Biobehav Rev 2011 May;35:1326-1341.
  69. Walker LC, Kastman HE, Koeleman JA, Smith CM, Perry CJ, Krstew EV, et al. Nucleus incertus corticotrophin-releasing factor 1 receptor signalling regulates alcohol seeking in rats. Addict Biol 2016 Jul 20 [Epub ahead of print]. http://dx.doi.org/10.1111/adb.12426.
  70. Kumar JR, Rajkumar R, Farooq U, Lee LC, Tan FC, Dawe GS. Evidence of D2 receptor expression in the nucleus incertus of the rat. Physiol Behav 2015;151:525-534. https://doi.org/10.1016/j.physbeh.2015.08.024
  71. Haidar M, Lam M, Chua BE, Smith CM, Gundlach AL. Sensitivity to chronic methamphetamine administration and withdrawal in mice with relaxin-3/RXFP3 Deficiency. Neurochem Res 2016; 41:481-491. https://doi.org/10.1007/s11064-015-1621-2
  72. Yehuda R, Daskalakis NP, Lehrner A, Desarnaud F, Bader HN, Makotkine I, et al. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring. Am J Psychiatry 2014;171:872-880. https://doi.org/10.1176/appi.ajp.2014.13121571

Cited by

  1. Violence and Abuse: What Child Psychiatrists Need to Know vol.28, pp.1, 2017, https://doi.org/10.5765/jkacap.2017.28.1.2