Abstract
Post-traumatic stress disorder (PTSD) is a severe polygenic disorder triggered by environmental factors. Many polymorphic genes, particularly the genetic determinants of hypodopaminergia (low dopamine function), associate with a predisposition to PTSD as well as substance use disorder. Support from the National Institutes of Health for neuroimaging research and molecular, genetic applied technologies has improved understanding of brain reward circuitry functions that have inspired the development of new innovative approaches to their early diagnosis and treatment of some PTSD symptomatology and addiction. This review presents psychosocial and genetic evidence that vulnerability or resilience to PTSD can theoretically be impacted by dopamine regulation. From a neuroscience perspective, dopamine is widely accepted as a major neurotransmitter. Questions about how to modulate dopamine clinically in order to treat and prevent PTSD and other types of reward deficiency disorders remain. Identification of genetic variations associated with the relevant genotype–phenotype relationships can be characterized using the Genetic Addiction Risk Score (GARS®) and psychosocial tools. Development of an advanced genetic panel is under study and will be based on a new array of genes linked to PTSD. However, for now, the recommendation is that enlistees for military duty be given the opportunity to voluntarily pre-test for risk of PTSD with GARS, before exposure to environmental triggers or upon return from deployment as part of PTSD management. Dopamine homeostasis may be achieved via customization of neuronutrient supplementation “Precision Behavioral Management” (PBM™) based on GARS test values and other pro-dopamine regulation interventions like exercise, mindfulness, biosensor tracking, and meditation.
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References
Bowirrat A, Chen TJ, Blum K, Madigan M, Bailey JA, Chuan Chen AL, Downs BW, Braverman ER et al (2010) Neuro-psychopharmacogenetics and neurological antecedents of posttraumatic stress disorder: unlocking the mysteries of resilience and vulnerability. Curr Neuropharmacol 8(4):335–358. https://doi.org/10.2174/157015910793358123
Jellinek E (1960) The disease concept of alcoholism. College and University Press, Italy, New Heaven
Davis VE, Walsh MJ (1970) Alcohol addiction and tetrahydropapaveroline. Science 169(3950):1105–1106
Hamilton MG, Blum K, Hirst M (1978) Identification of an isoquinoline alkaloid after chronic exposure to ethanol. Alcohol Clin Exp Res 2(2):133–137
Collins MA, Kahn AJ (1982) Attraction to ethanol solutions in mice: induction by a tetrahydroisoquinoline derivative of L-DOPA. Subst Alcohol Actions Misuse 3(5):299–302
Cohen G, Collins M (1970) Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism. Science 167(3926):1749–1751
Blum K, Hamilton MG, Hirst M, Wallace JE (1978) Putative role of isoquinoline alkaloids in alcoholism: a link to opiates. Alcohol Clin Exp Res 2(2):113–120
Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Cull JG, Comings DE (1996) The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med 89(7):396–400
Blum K (2017) Reward deficiency syndrome. The SAGE Encyclopedia of Abnormal and Clinical Psychology Sage Publications, Inc, University of Pennsylvania School of Medicine, USA
O’Doherty DCM, Tickell A, Ryder W, Chan C, Hermens DF, Bennett MR, Lagopoulos J (2017) Frontal and subcortical grey matter reductions in PTSD. Psychiatry Res Neuroimaging 266:1–9. https://doi.org/10.1016/j.pscychresns.2017.05.008
O’Doherty DC, Chitty KM, Saddiqui S, Bennett MR, Lagopoulos J (2015) A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Res 232(1):1–33. https://doi.org/10.1016/j.pscychresns.2015.01.002
Philip NS, Carpenter SL, Sweet LH (2014) Developing neuroimaging phenotypes of the default mode network in PTSD: integrating the resting state, working memory, and structural connectivity. J Vis Exp (89). doi:https://doi.org/10.3791/51651
Martindale SL, Rowland JA, Shura RD, Taber KH (2018) Longitudinal changes in neuroimaging and neuropsychiatric status of post-deployment veterans: a CENC pilot study. Brain Inj 32(10):1208–1216. https://doi.org/10.1080/02699052.2018.1492741
Averill LA, Abdallah CG, Pietrzak RH, Averill CL, Southwick SM, Krystal JH, Harpaz-Rotem I (2017) Combat exposure severity is associated with reduced cortical thickness in combat veterans: a preliminary report. Chronic stress (Thousand Oaks, Calif) 1. doi:https://doi.org/10.1177/2470547017724714
Akiki TJ, Averill CL, Wrocklage KM, Schweinsburg B, Scott JC, Martini B, Averill LA, Southwick SM, Krystal JH, Abdallah CG (2017) The association of PTSD symptom severity with localized Hippocampus and amygdala abnormalities. Chronic stress (Thousand Oaks, Calif) 1. doi:https://doi.org/10.1177/2470547017724069
van Wingen GA, Geuze E, Caan MW, Kozicz T, Olabarriaga SD, Denys D, Vermetten E, Fernandez G (2012) Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition. Proc Natl Acad Sci U S A 109(38):15508–15513. https://doi.org/10.1073/pnas.1206330109
Logue MW, van Rooij SJH, Dennis EL, Davis SL, Hayes JP, Stevens JS, Densmore M, Haswell CC et al (2018) Smaller hippocampal volume in posttraumatic stress disorder: a multisite ENIGMA-PGC study: subcortical volumetry results from posttraumatic stress disorder consortia. Biol Psychiatry 83(3):244–253. https://doi.org/10.1016/j.biopsych.2017.09.006
Butler O, Willmund G, Gleich T, Gallinat J, Kuhn S, Zimmermann P (2018) Hippocampal gray matter increases following multimodal psychological treatment for combat-related post-traumatic stress disorder. Brain and behavior 8(5):e00956. https://doi.org/10.1002/brb3.956
Nelson EC, Heath AC, Lynskey MT, Agrawal A, Henders AK, Bowdler LM, Todorov AA, Madden PA et al (2014) PTSD risk associated with a functional DRD2 polymorphism in heroin-dependent cases and controls is limited to amphetamine-dependent individuals. Addict Biol 19(4):700–707. https://doi.org/10.1111/adb.12062
Saunders EC, Lambert-Harris C, McGovern MP, Meier A, Xie H (2015) The prevalence of posttraumatic stress disorder symptoms among addiction treatment patients with cocaine use disorders. J Psychoactive Drugs 47(1):42–50. https://doi.org/10.1080/02791072.2014.977501
Dackis CA, Gold MS (1985) New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 9(3):469–477
Noble EP, Blum K, Khalsa ME, Ritchie T, Montgomery A, Wood RC, Fitch RJ, Ozkaragoz T et al (1993) Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend 33(3):271–285
Dackis CA, Gold MS, Sweeney DR, Byron JP Jr, Climko R (1987) Single-dose bromocriptine reverses cocaine craving. Psychiatry Res 20(4):261–264
Lawford BR, Young RM, Rowell JA, Qualichefski J, Fletcher BH, Syndulko K, Ritchie T, Noble EP (1995) Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1 allele. Nat Med 1(4):337–341
Bogomolova EV, Rauschenbach IY, Adonyeva NV, Alekseev AA, Faddeeva NV, Gruntenko NE (2010) Dopamine down-regulates activity of alkaline phosphatase in Drosophila: the role of D2-like receptors. J Insect Physiol 56(9):1155–1159. https://doi.org/10.1016/j.jinsphys.2010.03.014
Rouillard C, Bedard PJ, Falardeau P, Dipaolo T (1987) Behavioral and biochemical evidence for a different effect of repeated administration of L-dopa and bromocriptine on denervated versus non-denervated striatal dopamine receptors. Neuropharmacology 26(11):1601–1606
Blum K, Chen AL, Chen TJ, Braverman ER, Reinking J, Blum SH, Cassel K, Downs BW et al (2008) Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary. Theor Biol Med Model 5:24. https://doi.org/10.1186/1742-4682-5-24
Blum K, Oscar-Berman M, Stuller E, Miller D, Giordano J, Morse S, McCormick L, Downs WB et al (2012) Neurogenetics and nutrigenomics of neuro-nutrient therapy for reward deficiency syndrome (RDS): clinical ramifications as a function of molecular neurobiological mechanisms. J Addict Res Ther 3(5):139. https://doi.org/10.4172/2155-6105.1000139
Thanos PK, Rivera SN, Weaver K, Grandy DK, Rubinstein M, Umegaki H, Wang GJ, Hitzemann R et al (2005) Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. Life Sci 77(2):130–139. https://doi.org/10.1016/j.lfs.2004.10.061
Thanos PK, Michaelides M, Umegaki H, Volkow ND (2008) D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse (New York, NY) 62(7):481–486. https://doi.org/10.1002/syn.20523
Blum K, Febo M, Badgaiyan RD (2016) Fifty years in the development of a glutaminergic-dopaminergic optimization complex (KB220) to balance brain reward circuitry in reward deficiency syndrome: a pictorial. Austin addiction sciences 1 (2)
Febo M, Blum K, Badgaiyan RD, Baron D, Thanos PK, Colon-Perez LM, Demortrovics Z, Gold MS (2017) Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome. Frontiers in bioscience (Landmark edition) 22:669–691
Blum K, Liu Y, Wang W, Wang Y, Zhang Y, Oscar-Berman M, Smolen A, Febo M et al (2015) rsfMRI effects of KB220Z on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad Med 127(2):232–241
Blum K, Gardner E, Oscar-Berman M, Gold M (2012) “Liking” and “wanting” linked to reward deficiency syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry. Curr Pharm Des 18(1):113–118
Comings DE, Muhleman D, Gysin R (1996) Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: a study and replication. Biol Psychiatry 40(5):368–372. https://doi.org/10.1016/0006-3223(95)00519-6
Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH et al (1990) Allelic association of human dopamine D2 receptor gene in alcoholism. Jama 263(15):2055–2060
Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ (1991) Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 48(7):648–654
Blum K, Giordano J, Oscar-Berman M, Bowirrat A, Simpatico T, Barh D (2012) Diagnosis and healing in veterans suspected of suffering from post-traumatic stress disorder (PTSD) using reward gene testing and reward circuitry natural dopaminergic activation. J Genet Syndr Gene Ther 3(3):1000116. https://doi.org/10.4172/2157-7412.1000116
Roy-Byrne P, Arguelles L, Vitek ME, Goldberg J, Keane TM, True WR, Pitman RK (2004) Persistence and change of PTSD symptomatology--a longitudinal co-twin control analysis of the Vietnam Era Twin Registry. Soc Psychiatry Psychiatr Epidemiol 39(9):681–685. https://doi.org/10.1007/s00127-004-0810-0
Vaswani KK, Richard CW 3rd, Tejwani GA (1988) Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues. Pharmacol Biochem Behav 29(1):163–168
Szutorisz H, DiNieri JA, Sweet E, Egervari G, Michaelides M, Carter JM, Ren Y, Miller ML et al (2014) Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39(6):1315–1323. https://doi.org/10.1038/npp.2013.352
Auxemery Y (2012) Posttraumatic stress disorder (PTSD) as a consequence of the interaction between an individual genetic susceptibility, a traumatogenic event and a social context. Encephale 38(5):373–380. https://doi.org/10.1016/j.encep.2011.12.003
Rayman JB, Hijazi J, Li X, Kedersha N, Anderson PJ, Kandel ER (2019) Genetic perturbation of TIA1 reveals a physiological role in fear memory. Cell Rep 26(11):2970–2983.e2974. https://doi.org/10.1016/j.celrep.2019.02.048
Zhang K, Wang L, Cao C, Li G, Fang R, Liu P, Luo S, Zhang X et al (2018) A DRD2/ANNK1-COMT interaction, consisting of functional variants, confers risk of post-traumatic stress disorder in traumatized Chinese. Frontiers in psychiatry 9:170. https://doi.org/10.3389/fpsyt.2018.00170
Blum K, Chen ALC, Thanos PK, Febo M, Demetrovics Z, Dushaj K, Kovoor A, Baron D et al (2018) Genetic addiction risk score (GARS)™, a predictor of vulnerability to opioid dependence. Frontiers in bioscience (Elite edition) 10:175–196
Li L, Bao Y, He S, Wang G, Guan Y, Ma D, Wang P, Huang X et al (2016) The association between genetic variants in the dopaminergic system and posttraumatic stress disorder: a meta-analysis. Medicine (Baltimore) 95(11):e3074. https://doi.org/10.1097/md.0000000000003074
Tsang J, Fullard JF, Giakoumaki SG, Katsel P, Katsel P, Karagiorga VE, Greenwood TA, Braff DL et al (2015) The relationship between dopamine receptor D1 and cognitive performance. NPJ Schizophr 1:14002. https://doi.org/10.1038/npjschz.2014.2
Minichino A, Francesconi M, Carrion RE, Bevilacqua A, Parisi M, Rullo S, Ando A, Biondi M et al (2017) Prediction of functional outcome in young patients with a recent-onset psychiatric disorder: beyond the traditional diagnostic classification system. Schizophr Res 185:114–121. https://doi.org/10.1016/j.schres.2016.12.019
Zainal Abidin S, Tan EL, Chan SC, Jaafar A, Lee AX, Abd Hamid MH, Abdul Murad NA, Pakarul Razy NF et al (2015) DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients. BMC Neurol 15:59. https://doi.org/10.1186/s12883-015-0316-2
Prasad P, Ambekar A, Vaswani M (2013) Case-control association analysis of dopamine receptor polymorphisms in alcohol dependence: a pilot study in Indian males. BMC Res Notes 6:418. https://doi.org/10.1186/1756-0500-6-418
Reed JL, D’Ambrosio E, Marenco S, Ursini G, Zheutlin AB, Blasi G, Spencer BE, Romano R et al (2018) Interaction of childhood urbanicity and variation in dopamine genes alters adult prefrontal function as measured by functional magnetic resonance imaging (fMRI). PLoS One 13(4):e0195189. https://doi.org/10.1371/journal.pone.0195189
Hemmings SM, Martin LI, Klopper M, van der Merwe L, Aitken L, de Wit E, Black GF, Hoal EG et al (2013) BDNF Val66Met and DRD2 Taq1A polymorphisms interact to influence PTSD symptom severity: a preliminary investigation in a South African population. Prog Neuro-Psychopharmacol Biol Psychiatry 40:273–280. https://doi.org/10.1016/j.pnpbp.2012.10.011
Voisey J, Swagell CD, Hughes IP, Morris CP, van Daal A, Noble EP, Kann B, Heslop KA et al (2009) The DRD2 gene 957C>T polymorphism is associated with posttraumatic stress disorder in war veterans. Depress Anxiety 26(1):28–33. https://doi.org/10.1002/da.20517
Lawford BR, Young R, Noble EP, Kann B, Ritchie T (2006) The D2 dopamine receptor (DRD2) gene is associated with co-morbid depression, anxiety and social dysfunction in untreated veterans with post-traumatic stress disorder. European psychiatry : the journal of the Association of European Psychiatrists 21(3):180–185. https://doi.org/10.1016/j.eurpsy.2005.01.006
Rajan R, Krishnan S, Sarma G, Sarma SP, Kishore A (2018) Dopamine receptor D3 rs6280 is associated with aberrant decision-making in Parkinson’s disease. Movement disorders clinical practice 5(4):413–416. https://doi.org/10.1002/mdc3.12631
Oporto GH, Bornhardt T, Iturriaga V, Salazar LA (2018) Single nucleotide polymorphisms in genes of dopaminergic pathways are associated with bruxism. Clin Oral Investig 22(1):331–337. https://doi.org/10.1007/s00784-017-2117-z
Zhao C, Liu J, Gong P, Hu J, Zhou X (2016) Investigating the genetic basis of social conformity: the role of the dopamine receptor 3 (DRD3) gene. Neuropsychobiology 74(1):32–40. https://doi.org/10.1159/000450710
Kang SG, Lee BH, Lee JS, Chai YG, Ko KP, Lee HJ, Han DM, Ji H et al (2014) DRD3 gene rs6280 polymorphism may be associated with alcohol dependence overall and with Lesch type I alcohol dependence in Koreans. Neuropsychobiology 69(3):140–146. https://doi.org/10.1159/000358062
Bombin I, Arango C, Mayoral M, Castro-Fornieles J, Gonzalez-Pinto A, Gonzalez-Gomez C, Moreno D, Parellada M et al (2008) DRD3, but not COMT or DRD2, genotype affects executive functions in healthy and first-episode psychosis adolescents. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 147b(6):873–879. https://doi.org/10.1002/ajmg.b.30710
Dragan WL, Oniszczenko W (2009) The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors. Anxiety Stress Coping 22(5):483–495. https://doi.org/10.1080/10615800802419407
Armbruster D, Mueller A, Moser DA, Lesch KP, Brocke B, Kirschbaum C (2009) Interaction effect of D4 dopamine receptor gene and serotonin transporter promoter polymorphism on the cortisol stress response. Behav Neurosci 123(6):1288–1295. https://doi.org/10.1037/a0017615
Brody GH, Chen YF, Yu T, Beach SR, Kogan SM, Simons RL, Windle M, Philibert RA (2012) Life stress, the dopamine receptor gene, and emerging adult drug use trajectories: a longitudinal, multilevel, mediated moderation analysis. Dev Psychopathol 24(3):941–951. https://doi.org/10.1017/s0954579412000466
Bakermans-Kranenburg MJ, van IJzendoorn MH, Caspers K, Philibert R (2011) DRD4 genotype moderates the impact of parental problems on unresolved loss or trauma. Attach Hum Dev 13(3):253–269. https://doi.org/10.1080/14616734.2011.562415
Segman RH, Cooper-Kazaz R, Macciardi F, Goltser T, Halfon Y, Dobroborski T, Shalev AY (2002) Association between the dopamine transporter gene and posttraumatic stress disorder. Mol Psychiatry 7(8):903–907. https://doi.org/10.1038/sj.mp.4001085
Drury SS, Brett ZH, Henry C, Scheeringa M (2013) The association of a novel haplotype in the dopamine transporter with preschool age posttraumatic stress disorder. J Child Adolesc Psychopharmacol 23(4):236–243. https://doi.org/10.1089/cap.2012.0072
Hunnerkopf R, Strobel A, Gutknecht L, Brocke B, Lesch KP (2007) Interaction between BDNF Val66Met and dopamine transporter gene variation influences anxiety-related traits. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 32(12):2552–2560. https://doi.org/10.1038/sj.npp.1301383
Valente NL, Vallada H, Cordeiro Q, Miguita K, Bressan RA, Andreoli SB, Mari JJ, Mello MF (2011) Candidate-gene approach in posttraumatic stress disorder after urban violence: association analysis of the genes encoding serotonin transporter, dopamine transporter, and BDNF. J Mol Neurosci 44(1):59–67. https://doi.org/10.1007/s12031-011-9513-7
Havelka Mestrovic A, Tudor L, Nikolac Perkovic M, Nedic Erjavec G, Kovacic Petrovic Z, Svob Strac D, Konjevod M, Pivac N (2018) Significant association between catechol-O-methyltransferase (COMT) Val158/108Met polymorphism and cognitive function in veterans with PTSD. Neurosci Lett 666:38–43. https://doi.org/10.1016/j.neulet.2017.12.033
Deslauriers J, Acheson DT, Maihofer AX, Nievergelt CM, Baker DG, Geyer MA, Risbrough VB (2018) COMT val158met polymorphism links to altered fear conditioning and extinction are modulated by PTSD and childhood trauma. Depress Anxiety 35(1):32–42. https://doi.org/10.1002/da.22678
Winkler EA, Yue JK, Ferguson AR, Temkin NR, Stein MB, Barber J, Yuh EL, Sharma S et al (2017) COMT Val(158)met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury. J Clin Neurosci 35:109–116. https://doi.org/10.1016/j.jocn.2016.09.017
Humphreys KL, Scheeringa MS, Drury SS (2014) Race moderates the association of catechol-O-methyltransferase genotype and posttraumatic stress disorder in preschool children. J Child Adolesc Psychopharmacol 24(8):454–457. https://doi.org/10.1089/cap.2014.0077
Clark R, DeYoung CG, Sponheim SR, Bender TL, Polusny MA, Erbes CR, Arbisi PA (2013) Predicting post-traumatic stress disorder in veterans: interaction of traumatic load with COMT gene variation. J Psychiatr Res 47(12):1849–1856. https://doi.org/10.1016/j.jpsychires.2013.08.013
Boscarino JA, Erlich PM, Hoffman SN, Zhang X (2012) Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment. Neuropsychiatr Dis Treat 8:131–139. https://doi.org/10.2147/ndt.s29508
Zhang Y, Ming QS, Yi JY, Wang X, Chai QL, Yao SQ (2017) Gene-gene-environment interactions of serotonin transporter, monoamine oxidase a and childhood maltreatment predict aggressive behavior in Chinese adolescents. Front Behav Neurosci 11:17. https://doi.org/10.3389/fnbeh.2017.00017
Verhoeven FE, Booij L, Kruijt AW, Cerit H, Antypa N, Does W (2012) The effects of MAOA genotype, childhood trauma, and sex on trait and state-dependent aggression. Brain and behavior 2(6):806–813. https://doi.org/10.1002/brb3.96
Frazzetto G, Di Lorenzo G, Carola V, Proietti L, Sokolowska E, Siracusano A, Gross C, Troisi A (2007) Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype. PLoS One 2(5):e486. https://doi.org/10.1371/journal.pone.0000486
Mehta D, Voisey J, Bruenig D, Harvey W, Morris CP, Lawford B, Young RM (2018) Transcriptome analysis reveals novel genes and immune networks dysregulated in veterans with PTSD. Brain Behav Immun 74:133–142. https://doi.org/10.1016/j.bbi.2018.08.014
Tian Y, Liu H, Guse L, Wong TK, Li J, Bai Y, Jiang X (2015) Association of genetic factors and gene-environment interactions with risk of developing posttraumatic stress disorder in a case-control study. Biological research for nursing 17(4):364–372. https://doi.org/10.1177/1099800415588362
Liu Y, Garrett ME, Dennis MF, Green KT, Ashley-Koch AE, Hauser MA, Beckham JC, Kimbrel NA (2015) An examination of the association between 5-HTTLPR, combat exposure, and PTSD diagnosis among U.S. veterans. PLoS One 10(3):e0119998. https://doi.org/10.1371/journal.pone.0119998
Walsh K, Uddin M, Soliven R, Wildman DE, Bradley B (2014) Associations between the SS variant of 5-HTTLPR and PTSD among adults with histories of childhood emotional abuse: results from two African American independent samples. J Affect Disord 161:91–96. https://doi.org/10.1016/j.jad.2014.02.043
Gressier F, Calati R, Balestri M, Marsano A, Alberti S, Antypa N, Serretti A (2013) The 5-HTTLPR polymorphism and posttraumatic stress disorder: a meta-analysis. J Trauma Stress 26(6):645–653. https://doi.org/10.1002/jts.21855
Xie P, Kranzler HR, Farrer L, Gelernter J (2012) Serotonin transporter 5-HTTLPR genotype moderates the effects of childhood adversity on posttraumatic stress disorder risk: a replication study. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 159b(6):644–652. https://doi.org/10.1002/ajmg.b.32068
Morey RA, Hariri AR, Gold AL, Hauser MA, Munger HJ, Dolcos F, McCarthy G (2011) Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder. BMC psychiatry 11:76. https://doi.org/10.1186/1471-244x-11-76
Grabe HJ, Spitzer C, Schwahn C, Marcinek A, Frahnow A, Barnow S, Lucht M, Freyberger HJ et al (2009) Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. Am J Psychiatry 166(8):926–933. https://doi.org/10.1176/appi.ajp.2009.08101542
Carver CS, Johnson SL, Kim Y (2016) Mu opioid receptor polymorphism, early social adversity, and social traits. Soc Neurosci 11(5):515–524. https://doi.org/10.1080/17470919.2015.1114965
Slavich GM, Tartter MA, Brennan PA, Hammen C (2014) Endogenous opioid system influences depressive reactions to socially painful targeted rejection life events. Psychoneuroendocrinology 49:141–149. https://doi.org/10.1016/j.psyneuen.2014.07.009
Feusner J, Ritchie T, Lawford B, Young RM, Kann B, Noble EP (2001) GABA(A) receptor beta 3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population. Psychiatry Res 104(2):109–117
Javidi H, Yadollahie M (2012) Post-traumatic stress disorder. The international journal of occupational and environmental medicine 3(1):2–9
Diagnostic and statistical manual of mental disorders (2013). Fifth edn. American Psychiatric Association, Alexandria, VA
Cheney AM, Koenig CJ, Miller CJ, Zamora K, Wright P, Stanley R, Fortney J, Burgess JF et al (2018) Veteran-centered barriers to VA mental healthcare services use. BMC Health Serv Res 18(1):591. https://doi.org/10.1186/s12913-018-3346-9
Gallaway MS, Bell MR, Lagana-Riordan C, Fink DS, Meyer CE, Millikan AM (2013) The association between US Army enlistment waivers and subsequent behavioral and social health outcomes and attrition from service. Mil Med 178(3):261–266. https://doi.org/10.7205/milmed-d-12-00316
Brown LA, Gallagher T, Petersen J, Benhamou K, Foa EB, Asnaani A (2018) Does CBT for anxiety-related disorders alter suicidal ideation? Findings from a naturalistic sample. J Anxiety Disord 59:10–16. https://doi.org/10.1016/j.janxdis.2018.08.001
Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J (2012) Substance misuse of gabapentin. The British journal of general practice : the journal of the Royal College of General Practitioners 62(601):406–407. https://doi.org/10.3399/bjgp12X653516
Fond G, Loundou A, Rabu C, Macgregor A, Lancon C, Brittner M, Micoulaud-Franchi JA, Richieri R et al (2014) Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology 231(18):3663–3676. https://doi.org/10.1007/s00213-014-3664-5
McLaughlin T, Blum K, Oscar-Berman M, Febo M, Demetrovics Z, Agan G, Fratantonio J, Gold MS (2015) Using the neuroadaptagen KB200z to ameliorate terrifying, lucid nightmares in RDS patients: the role of enhanced, brain-reward, functional connectivity and dopaminergic homeostasis. J Reward Defic Syndr 1(1):24–35. https://doi.org/10.17756/jrds.2015-006
McLaughlin T, Blum K, Oscar-Berman M, Febo M, Agan G, Fratantonio JL, Simpatico T, Gold MS (2015) Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy. J Behav Addict 4(2):106–115. https://doi.org/10.1556/2006.4.2015.008
McLaughlin T, Febo M, Badgaiyan RD, Barh D, Dushaj K, Braverman ER, Li M, Madigan MA et al (2016) KB220Z™ a pro-dopamine regulator associated with the protracted, alleviation of terrifying lucid dreams. Can we infer neuroplasticity-induced changes in the reward circuit? J Reward Defic Syndr Addict Sci 2(1):3–13
Febo M, Blum K, Badgaiyan RD, Perez PD, Colon-Perez LM, Thanos PK, Ferris CF, Kulkarni P et al (2017) Enhanced functional connectivity and volume between cognitive and reward centers of naive rodent brain produced by pro-dopaminergic agent KB220Z. PLoS One 12(4):e0174774. https://doi.org/10.1371/journal.pone.0174774
Naifeh JA, Mash HBH, Stein MB, Fullerton CS, Kessler RC, Ursano RJ (2019) The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS): progress toward understanding suicide among soldiers. Mol Psychiatry 24(1):34–48. https://doi.org/10.1038/s41380-018-0197-z
McLaughlin T, Oscar-Berman M, Simpatico T, Giordano J, Jones S, Barh D, Downs WB, Waite RL et al (2013) Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette’s syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT). J Behav Addict 2(2):117–124. https://doi.org/10.1556/jba.2.2013.2.8
Thanos PK, Hamilton J, O’Rourke JR, Napoli A, Febo M, Volkow ND, Blum K, Gold M (2016) Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior. Oncotarget. https://doi.org/10.18632/oncotarget.8088
Starkman BG, Sakharkar AJ, Pandey SC (2012) Epigenetics-beyond the genome in alcoholism. Alcohol Res 34(3):293–305
Sheppard CW, Smith DE, Gay GR (1972) The changing face of heroin addiction in the Haight-Ashbury. Int J Addict 7(1):109–122
Fields HL, Margolis EB (2015) Understanding opioid reward. Trends Neurosci 38(4):217–225. https://doi.org/10.1016/j.tins.2015.01.002
Acknowledgments
We acknowledge editorial assistance from Margaret Madigan.
Funding
Research directed toward improving substance use disorders, especially in under-served populations, is the basis of an NIH grant awarded to Dr. Kenneth Blum and Marjorie Gondré-Lewis (Drs. Blum and Gondré-Lewis are the recipients of 1R41MD012318-01/MD/NIMHD NIH HHS/USA). Dr. R.D. Badgaiyan is partially supported by the National Institutes of Health grants 1R01NS073884 and 1R21MH073624; and VA Merit Review Awards CX000479 and CX000780. Dr. P. K. Thanos is the recipient of R01HD70888-01A1.
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Blum, K., Gondré-Lewis, M.C., Modestino, E.J. et al. Understanding the Scientific Basis of Post-traumatic Stress Disorder (PTSD): Precision Behavioral Management Overrides Stigmatization. Mol Neurobiol 56, 7836–7850 (2019). https://doi.org/10.1007/s12035-019-1600-8
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DOI: https://doi.org/10.1007/s12035-019-1600-8
Keywords
- Post-traumatic stress disorder (PTSD)
- Genetic addiction risk score (GARS™)
- Pro-dopamine regulation (KB220PAM)
- Hypodopaminergia
- Neuronutrient