No association between the serotonin transporter linked polymorphic region polymorphism and severity of posttraumatic stress disorder symptoms in combat veterans with or without comorbid depression

Psychiatry Research

Volumn 244, Issue , 2016, Pages 376-381

  Kovacic Petrovic, Zrnka ^a,b   Nedic Erjavec, Gordana ^c   Nikolac Perkovic, Matea ^c   Peraica, Tina ^d   Pivac, Nela ^c  

^a UNIVERSITY OF ZAGREB   (Croatia)

^b Referentni centar za Alzheimerovu bolest i psihijatriju sta rijeivo t ne dobi   (Croatia)

^c RUDER BO KOVI INSTITUTE   (Croatia)

^d University of Zagreb   (Croatia)

Author keywords

5 HTTLPR; Combat veterans; Comorbid depression; Platelet 5 HT concentration; Symptom severity

Indexed keywords

SEROTONIN; SEROTONIN TRANSPORTER;

ADULT; ARTICLE; CLINICIAN ADMINISTERED PTSD SCALE; CONTROLLED STUDY; DEPRESSION; DISEASE SEVERITY; DSM-IV; GENETIC POLYMORPHISM; GENOTYPE; HAMILTON DEPRESSION RATING SCALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MENTAL DISEASE ASSESSMENT; POLYMERASE CHAIN REACTION; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; SPECTROFLUOROMETRY; VETERAN; COMORBIDITY; COMPARATIVE STUDY; CROSS-SECTIONAL STUDY; GENETICS; MIDDLE AGED; PSYCHOLOGY; QUESTIONNAIRE; SEVERITY OF ILLNESS INDEX;

ADULT; COMBAT DISORDERS; COMORBIDITY; CROSS-SECTIONAL STUDIES; DEPRESSION; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, GENETIC; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEVERITY OF ILLNESS INDEX; STRESS DISORDERS, POST-TRAUMATIC; SURVEYS AND QUESTIONNAIRES; VETERANS;

EID: 84981505087     PISSN: 01651781     EISSN: 18727123     Source Type: Journal    
DOI: 10.1016/j.psychres.2016.08.017     Document Type: Article

References (53)

1. Arcel, L.T., Folnegovic-Smalc, V., Tocilj Simunkovic, G., Kozaric-Kovacic, D., Ljubotina, D., Ethnic cleansing and post-traumatic coping-war violence, PTSD, depression, anxiety and coping in Bosnian and Croatian refugees. A transactional approach. Arcel, L.T., (eds.) War, violence, Trauma, and the Coping Process: Armed Conflict in Europe and Survivor Response, 1998, IRCT, Copenhagen, 47–78.
2. Blake, D.D., Weathers, F.W., Nagy, L.M., Kaloupek, D.G., Gusman, F.D., Charney, D.S., Keane, T.M., The development of a Clinician-Administered PTSD Scale. J. Trauma Stress 8 (1995), 75–90.
3. Brinker, M., Westermeyer, J., Thuras, P., Canive, J., Severity of combat-related posttraumatic stress disorder versus noncombat-related posttraumatic stress disorder: a community-based study in American Indian and Hispanic veterans. J. Nerv. Ment. Dis. 195 (2007), 655–661.
4. Camacho, A., Dimsdale, J.E., Platelets and psychiatry: lessons learned from old and new studies. Psychosom. Med. 62 (2000), 326–336.
5. Faul, F., Erdfelder, E., Lang, A.G., Buchner, A., G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods 39 (2007), 175–191.
6. Field, A.P., Miles, J., Field, F., Discovering Statistics Using R. 2012, SAGE Publications Ltd., London, UK.
7. First, M.B., Spitzer, R.L., Williams, J.B.W., Gibbons, M., Structured Clinical Interview for DSM-IV-Patient Edition (SCID-P). 1995, American Psychiatric Press, Washington, DC.
8. Goenjian, A.K., Bailey, J.N., Walling, D.P., Steinberg, A.M., Schmidt, D., Dandekar, U., Noble, E.P., Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms. J. Affect. Disord. 140 (2012), 244–252.
9. Grabe, H.J., Schwahn, C., Mahler, J., Schulz, A., Spitzer, C., Fenske, K., Appel, K., Barnow, S., Nauck, M., Schomerus, G., Biffar, R., Rosskopf, D., John, U., Veolzke, H., Freyberger, H.J., Moderation of adult depression by the serotonin transporter promoter variant (5-HTTLPR), childhood abuse and adult traumatic events in a general population sample. Am. J. Med. Genet. Part B 159B (2012), 298–309.
10. Grabe, H.J., Spitzer, C., Schwahn, C., Marcinek, A., Frahnow, A., Barnow, S., Lucht, M., Freyberger, H.J., John, U., Wallaschofski, H., Volzke, H., Rosskopf, D., Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. Am. J. Psychiatry 166 (2009), 926–933.
11. Gressier, F., Calati, R., Balestri, M., Marsano, A., Alberti, S., Antypa, N., Serretti, A., The 5-HTTLPR polymorphism and posttraumatic stress disorder: a meta-analysis. J. Trauma Stress 26 (2013), 645–653.
12. Hamilton, M., A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23 (1960), 56–62.
13. Jacobs, B.L., Serotonin and behavior: emphasis on motor control. J. Clin. Psychiatry 52:Suppl (1991), S17–S23.
14. Jovanovic, T., Ressler, K.J., How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. Am. J. Psychiatry 167 (2010), 648–662.
15. Karg, K., Burmeister, M., Shedden, K., Sen, S., The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch. Gen. Psychiatry 68 (2011), 444–454.
16. Kessler, R.C., Sonnega, A., Bromet, E., Hughes, M., Nelson, C.B., Posttraumatic stress disorder in the National Comorbidity Survey. Arch. Gen. Psychiatry 52 (1995), 1048–1060.
17. Kenna, G.A., Roder-Hanna, N., Leggio, L., Zywiak, W.H., Clifford, J., Edwards, S., Kenna, J.A., Shoaff, J., Swift, R.M., Association of the 5-HTT gene-linked promoter region (5-HTTLPR) polymorphism with psychiatric disorders: review of psychopathology and pharmacotherapy. Pharmgenomics Pers. Med. 5 (2012), 19–35.
18. Kilpatrick, D.G., Koenen, K.C., Ruggiero, K.J., Acierno, R., Galea, S., Resnick, H.S., Roitzsch, J., Boyle, J., Gelernter, J., The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. Am. J. Psychiatry 164 (2007), 1693–1699.
19. Koenen, K.C., Aiello, A.E., Bakshis, E., Amstadter, A.B., Ruggiero, K.J., Acierno, R., Kilpatrick, D.G., Gelernter, J., Galea, S., Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment. Am. J. Epidemiol. 169 (2009), 704–711.
20. Kolassa, I.T., Ertl, V., Eckart, C., Glockner, F., Kolassa, S., Papassotiropoulos, A., de Quervain, D.J., Elbert, T., Association study of trauma load and SLC6A4 promoter polymorphism in posttraumatic stress disorder: evidence from survivors of the Rwandan genocide. J. Clin. Psychiatry 71 (2010), 543–547.
21. Kovacic, Z., Serotonin Transporter Linked Polymorphic Region (5-HTTLPR) in Patients with PTSD (Ph.D. thesis). 2010, School of Medicine, University of Zagreb, Zagreb (in Croatian).
22. Kovacic, Z., Henigsberg, N., Pivac, N., Nedic, G., Borovecki, A., Platelet serotonin concentration and suicidal behavior in combat related posttraumatic stress disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 32 (2008), 544–551.
23. Kozaric-Kovacic, D., Psychopharmacotherapy of posttraumatic stress disorder. Croat. Med. J. 49 (2008), 459–475.
24. Lee, H.J., Lee, M.S., Kang, R.H., Kim, H., Kim, S.D., Kee, B.S., Kim, Y.H., Kim, Y.K., Kim, J.B., Yeon, B.K., Oh, K.S., Oh, B.H., Yoon, J.S., Lee, C., Jung, H.Y., Chee, I.S., Paik, I.H., Influence of the serotonin transporter promoter gene polymorphism on susceptibility to posttraumatic stress disorder. Depression Anxiety 21 (2005), 135–139.
25. Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., Benjamin, J., Muller, C.R., Hamer, D.H., Murphy, D.L., Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274 (1996), 1527–1531.
26. Lesch, K.P., Gutknecht, L., Pharmacogenetics of the serotonin transporter. Prog. Neuropsychopharmacol. Biol. Psychiatry 29 (2005), 1062–1073.
27. Lipsky, R.H., Hu, X.Z., Goldman, D., Additional functional variation at the SLC6A4 gene. Am. J. Med. Genet. B: Neuropsychiatr. Genet., 150B, 2009, 153.
28. Liu, Y., Garrett, M.E., Dennis, M.F., Green, K.T., Ashley-Koch, A.E., Hauser, M.A., Beckham, J.C., Kimbrel, N.A., An examination of the association between 5-HTTLPR, combat exposure, and PTSD diagnosis among U.S. veterans, Plos One, 10, 2015, e0119998.
29. Lopez-Leon, S., Janssens, A.C., Gonzalez-Zuloeta Ladd, A.M., Del-Favero, J., Claes, S.J., Oostra, B.A., van Duijn, C.M., Meta-analyses of genetic studies on major depressive disorder. Mol. Psychiatry 13 (2008), 772–785.
30. Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193 (1951), 265–275.
31. Michopoulos, V., Norrholm, S.D., Jovanovic, T., Diagnostic biomarkers for posttraumatic stress disorder: promising horizons from translational neuroscience research. Biol. Psychiatry 78 (2015), 344–353.
32. Miller, S.A., Dykes, D.D., Polesky, H.F., A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res., 16, 1988, 1215.
33. Muck-Seler, D., Pivac, N., Jakovljevic, M., Sagud, M., Mihaljevic-Peles, A., Platelet 5-HT concentration and comorbid depression in war veterans with and without posttraumatic stress disorder. J. Affect. Disord. 75 (2003), 171–179.
34. Munafo, M.R., Durrant, C., Lewis, G., Flint, J., Gene X environment interactions at the serotonin transporter locus. Biol. Psychiatry 65 (2009), 211–219.
35. Navarro-Mateu, F., Escamez, T., Koenen, K.C., Alonso, J., Sanchez-Meca, J., Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder. PLoS One, 8, 2013, e66227.
36. Noskova, T., Pivac, N., Nedic, G., Kazantseva, A., Gaysina, D., Faskhutdinova, G., Gareeva, A., Khalilova, Z., Khusnutdinova, E., Kovacic, D.K., Kovacic, Z., Jokic, M., Seler, D.M., Ethnic differences in the serotonin transporter polymorphism (5-HTTLPR) in several European populations. Prog. Neuropsychopharmacol. Biol. Psychiatry 32 (2008), 1735–1739.
37. Pivac, N., Jakovljevic, M., Muck-Seler, D., Brzovic, Z., Hypothalamic-pituitary-adrenal axis activity and platelet 5-HT concentrations in depressed patients. Psychiatry Res. 73 (1997), 123–132.
38. Pivac, N., Kozaric-Kovacic, D., Mustapic, M., Dezeljin, M., Borovecki, A., Grubisic-Ilic, M., Muck-Seler, D., Platelet serotonin in combat related posttraumatic stress disorder with psychotic symptoms. J. Affect. Disord. 93 (2006), 223–227.
39. Pivac, N., Muck-Seler, D., Sagud, M., Jakovljevic, M., Platelet serotonergic markers in posttraumatic stress disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 26 (2002), 1193–1198.
40. Pivac, N., Nedic, G., Mustapic, M., Babic, A., Stipcevic, T., Borovecki, F., Hajnsek, S., Muck-Seler, D., The lack of genotype-phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects. Neurosci. Lett. 462 (2009), 45–48.
41. Risch, N., Herrell, R., Lehner, T., Liang, K.Y., Eaves, L., Hoh, J., Griem, A., Kovacs, M., Ott, J., Merikangas, K.R., Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301 (2009), 2462–2471.
42. Sagud, M., Nikolac Perkovic, M., Vuksan-Cusa, B., Maravic, A., Svob Strac, D., Mihaljevic Peles, A., Zivkovic, M., Kusevic, Z., Pivac, N., A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment. Psychopharmacology, 2016, 10.1007/s00213-016-4364-0.
43. Sayin, A., Kucukyildirim, S., Akar, T., Bakkaloglu, Z., Demircan, A., Kurtoglu, G., Demirel, B., Candansayar, S., Mergen, H., A prospective study of serotonin transporter gene promoter (5-HTT gene linked polymorphic region) and intron 2 (variable number of tandem repeats) polymorphisms as predictors of trauma response to mild physical injury. DNA Cell Biol. 29 (2010), 71–77.
44. Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A., Ressler, K.J., Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacol. Ther. 149 (2015), 150–190.
45. Stahl, S.M., Platelets as pharmacological models for the receptors and biochemistry of monoaminergic neurons. Longenecker, G.L., (eds.) Platelets: Physiology and Pharmacology, 1985, Academic Press, New York, 307–340.
46. Thakur, G.A., Joober, R., Brunet, A., Development and persistence of posttraumatic stress disorder and the 5-HTTLPR polymorphism. J. Trauma Stress 22 (2009), 240–243.
47. Wang, Z., Baker, D.G., Harrer, J., Hamner, M., Price, M., Amstadter, A., The relationship between combat-related posttraumatic stress disorder and the 5-HTTLPR/rs25531 polymorphism. Depression Anxiety 28 (2011), 1067–1073.
48. Weiss, S.J., Neurobiological alterations associated with traumatic stress. Perspect. Psychiatr. Care 43 (2007), 114–122.
49. Xie, P., Kranzler, H.R., Farrer, L., Gelernter, J., Serotonin transporter 5-HTTLPR genotype moderates the effects of childhood adversity on posttraumatic stress disorder risk: a replication study. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 159B (2012), 644–652.
50. Xie, P., Kranzler, H.R., Poling, J., Stein, M.B., Anton, R.F., Brady, K., Weiss, R.D., Farrer, L., Gelernter, J., Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Arch. Gen. Psychiatry 66 (2009), 1201–1209.
51. Yubero-Lahoz, S., Robledo, P., Farre, M., de laTorre, R., Platelet SERT as a peripheral biomarker of serotonergic neurotransmission in the central nervous system. Curr. Med. Chem. 20 (2013), 1382–1396.
52. Zahn, D., Petrak, F., Franke, L., Hagele, A.K., Juckel, G., Lederbogen, F., Neubauer, H., Norra, C., Uhl, I., Herpertz, S., Cortisol, platelet serotonin content, and platelet activity in patients with major depression and type 2 diabetes: an exploratory investigation. Psychosom. Med. 77 (2015), 145–155.
53. Zoladz, P.R., Diamond, D.M., Current status on behavioral and biological markers of PTSD: a search for clarity in a conflicting literature. Neurosci. Biobehav. Rev. 37 (2013), 860–895.