Interaction of Val66Met BDNF and 5-1 HTTLPR polymorphisms with prevalence of post2 earthquake 27-F PTSD in Chilean population

Juan Luis Castillo Navarrete; Benjamín Vicente; Kristin Schmidt; Esteban Moraga Escobar; Romina Rojas Ponce; Paola Lagos; Ximena Macaya; Alejandra Guzmán Castillo

doi:10.29393/ppudec-1IVCN00801

##article.authors##

Juan Luis Castillo Navarrete Departamento de Tecnología Médica, Facultad de Medicina, Universidad de Concepción, Concepción, Chile.
Benjamín Vicente Programa Neurociencias, Psiquiatría y Salud Mental, NEPSAM, Universidad de Concepción
Kristin Schmidt Programa Neurociencias, Psiquiatría y Salud Mental, NEPSAM, Universidad de Concepción. 10 Concepción, Chile (http://nepsam.udec.cl/)
Esteban Moraga Escobar Programa Neurociencias, Psiquiatría y Salud Mental, NEPSAM, Universidad de Concepción. Concepción, Chile (http://nepsam.udec.cl/)
Romina Rojas Ponce Programa Neurociencias, Psiquiatría y Salud Mental, NEPSAM, Universidad de Concepción. Concepción, Chile (http://nepsam.udec.cl/)
Paola Lagos Programa Neurociencias, Psiquiatría y Salud Mental, NEPSAM, Universidad de Concepción. Concepción, Chile (http://nepsam.udec.cl/)
Ximena Macaya Programa Neurociencias, Psiquiatría y Salud Mental, NEPSAM, Universidad de Concepción. Concepción, Chile (http://nepsam.udec.cl/)
Alejandra Guzmán Castillo Departamento de Ciencias Básicas y Morfología, Facultad de Medicina, Universidad Católica de la Santísima Concepción, Concepción, Chile

DOI:

https://doi.org/10.29393/ppudec-1IVCN00801

Keywords:

Child Maltreatment, Earthquake, Tsunami, Posttraumatic stress disorder, Depresive episode

Resumen

Abstract
Natural disasters can have significant impacts on populations, including an increased risk of developing post-traumatic stress disorder (PTSD). This study aimed to investigate the prevalence of PTSD in individuals who had previously undergone structured psychiatric diagnostic interviews in the aftermath of the 27-F earthquake in Chile. The prevalence of post-earthquake PTSD was found to be 11.06%, with no significant difference from the reported prevalence of PTSD in those exposed to traumatic events. While studies have identified higher rates of PTSD in women, this study did not find any sex related differences. However, a concomitant diagnosis of depressive episodes (DE) was significantly associated with an elevated risk of developing post earthquake PTSD. Witnessing more than one critical traumatic event associated with the earthquake was also found to escalate the risk of developing earthquake-induced PTSD. The study also evaluated the potential influence of genetic factors on the risk of post-earthquake PTSD. The presence of BDNF and 5-HTTLPR genetic variants was assessed, and although studies have proposed that carriers of the Met allele are more susceptible to developing PTSD, this study did not identify a significant association between the Met allele and the incidence of post-earthquake PTSD. Similarly, while studies have suggested that individuals carrying at least one "S" allele of 5-HTTLPR are more susceptible to stress-related disorders, this study did not find a significant association between the LG and S alleles and the incidence of post-earthquake PTSD. The study highlights the need for clinical care to prioritize the detection and treatment of concomitant DE and the exposure to critical traumatic events in survivors of disasters. Early interventions can potentially mitigate the risk of developing post-disaster PTSD. Furthermore, the study suggests a need for a more comprehensive understanding of genetic predispositions to post-disaster PTSD, and future research is encouraged to explore other genetic variants that could influence the development of PTSD. Limitations of the study include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. These limitations highlight the need for further research to broaden the understanding of PTSD following disasters, potentially leading to more effective prevention and treatment strategies. In conclusion, this study emphasizes the multifaceted nature of PTSD and the significant role that critical traumatic experiences and concomitant depressive episodes play in the development of postdisaster PTSD. The study provides insights into potential areas for intervention and highlights the need for further research to better understand the relationship between genetic factors and post-disaster PTSD.

Citas

• Abeldaño, R. A., Fernández, A. R., Estario, J. C., Enders, J. E., & De López Neira, M. J. (2014). Screening de trastornos de estrés postraumático en población afectada por el terremoto chileno de 2010. Cadernos de Saúde Pública, 30(11), 2377–2386. https://doi.org/10.1590/0102-311X00141313

• Aksu, S., Unlu, G., Kardesler, A. C., Cakaloz, B., & Aybek, H. (2018). Altered levels of brain-derived neurotrophic factor, proBDNF and tissue plasminogen activator in children with posttraumatic stress disorder. Psychiatry Research, 268, 478–483. https://doi.org/10.1016/J.PSYCHRES.2018.07.013

• Alisic, E., Zalta, A. K., Van Wesel, F., Larsen, S. E., Hafstad, G. S., Hassanpour, K., & Smid, G. E. (2014). Rates of post-traumatic stress disorder in trauma-exposed children and adolescents: Meta-analysis. British Journal of Psychiatry, 204(5), 335–340. https://doi.org/10.1192/BJP.BP.113.131227

• Andero, R., & Ressler, K. J. (2012). Fear extinction and BDNF: translating animal models of PTSD to the clinic. Genes, Brain and Behavior, 11(5), 503–512. https://doi.org/10.1111/J.1601-183X.2012.00801.X

• Andrews, G., & Peters, L. (1998). The psychometric properties of the Composite International Diagnostic Interview. Social Psychiatry and Psychiatric Epidemiology 1998 33:2, 33(2), 80–88. https://doi.org/10.1007/S001270050026

• Benítez, C. I. P., Vicente, B., Zlotnick, C., Kohn, R., Johnson, J., Valdivia, S., & Rioseco, P. (2009). Estudio epidemiológico de sucesos traumáticos, trastorno de estrés post-traumático y otros trastornos psiquiátricos en una muestra representativa de Chile. Salud Mental (Mexico City, Mexico), 32(2), 145. /pmc/articles/PMC2990643/

• Bountress, K. E., Bacanu, S. A., Tomko, R. L., Korte, K. J., Hicks, T., Sheerin, C., Lind, M. J., Marraccini, M., Nugent, N., & Amstadter, A. B. (2017). The Effects of a BDNF Val66Met Polymorphism on Posttraumatic Stress Disorder: A Meta-Analysis. Neuropsychobiology, 76(3), 136–142. https://doi.org/10.1159/000489407

• Breslau, N., & Anthony, J. C. (2007). Gender differences in the sensitivity to posttraumatic stress disorder: An epidemiological study of urban young adults. Journal of Abnormal Psychology, 116(3), 607–611. https://doi.org/10.1037/0021-843X.116.3.607

• Bruenig, D., Lurie, J., Morris, C. P., Harvey, W., Lawford, B., Young, R. M. D., & Voisey, J. (2016). A case-control study and meta-analysis reveal BDNF Val66Met is a possible risk factor for PTSD. Neural Plasticity, 2016. https://doi.org/10.1155/2016/6979435

• Campos, B., Vinder, V., Passos, R. B. F., Coutinho, E. S. F., Vieira, N. C. P., Leal, K. B., Mendlowicz, M. V., Figueira, I., Luz, M. P., Marques-Portela, C., Vilete, L. M. P., & Berger, W. (2022). To BDZ or not to BDZ? That is the question! Is there reliable scientific evidence for or against using benzodiazepines in the aftermath of potentially traumatic events for the prevention of PTSD? A systematic review and meta-analysis. Journal of Psychopharmacology, 36(4), 449–459. https://doi.org/10.1177/02698811221080464

• Carr, C. P., Martins, C. M. S., Stingel, A. M., Lemgruber, V. B., & Juruena, M. F. (2013). The role of early life stress in adult psychiatric disorders: a systematic review according to childhood trauma subtypes. The Journal of Nervous and Mental Disease, 201(12), 1007–1020. https://doi.org/10.1097/NMD.0000000000000049

• Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H. L., McClay, J., Mill, J., Martin, J., Braithwaite, A., & Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301(5631), 386–389. https://doi.org/10.1126/SCIENCE.1083968

• Castro-Vale, I., & Carvalho, D. (2020). healthcare The Pathways between Cortisol-Related Regulation Genes and PTSD Psychotherapy. Healtcare, 8(4), 376. https://doi.org/10.3390/healthcare8040376

• De Berardis, D., Marini, S., Serroni, N., Iasevoli, F., Tomasetti, C., Bartolomeis, A., Mazza, M., Tempesta, D., Valchera, A., Fornaro, M., Pompili, M., Sepede, G., Vellante, F., Orsolini, L., Martinotti, G., & Giannantonio, M. (2015). Targeting the Noradrenergic System in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis of Prazosin Trials. Current Drug Targets, 16(10), 1094–1106. https://doi.org/10.2174/1389450116666150506114108

• De Berardis, D., Vellante, F., Fornaro, M., Anastasia, A., Olivieri, L., Rapini, G., Serroni, N., Orsolini, L., Valchera, A., Carano, A., Tomasetti, C., Varasano, P. A., Pressanti, G. L., Bustini, M., Pompili, M., Serafini, G., Perna, G., Martinotti, G., & Di Giannantonio, M. (2019). Alexithymia, suicide ideation, affective temperaments and homocysteine levels in drug naïve patients with post-traumatic stress disorder: an exploratory study in the everyday ‘real world’ clinical practice. Https://Doi.Org/10.1080/13651501.2019.1699575, 24(1), 83–87. https://doi.org/10.1080/13651501.2019.1699575

• Díaz, C. A., Quintana, G. R., & Vogel, E. H. (2012). Depression, anxiety and post-traumatic stress disorder symptoms in adolescents seven months after the february 27 2010 earthquake in Chile. Terapia Psicológica, 30(1), 37–43. https://doi.org/10.4067/S0718-48082012000100004

• Dorrington, S., Zavos, H., Ball, H., McGuffin, P., Sumathipala, A., Siribaddana, S., Rijsdijk, F., Hatch, S. L., & Hotopf, M. (2019). Family functioning, trauma exposure and PTSD: A cross sectional study. Journal of Affective Disorders, 245, 645–652. https://doi.org/10.1016/J.JAD.2018.11.056

• Fernandez, C. A., Choi, K. W., Marshall, B. D. L., Vicente, B., Saldivia, S., Kohn, R., Koenen, K. C., Arheart, K. L., & Buka, S. L. (2020). Assessing the relationship between psychosocial stressors and psychiatric resilience among Chilean disaster survivors. The British Journal of Psychiatry, 217(5), 630–637. https://doi.org/10.1192/BJP.2020.88

• Fernandez, C. A., Vicente, B., Marshall, B. D. L., Koenen, K. C., Arheart, K. L., Kohn, R., Saldivia, S., & Buka, S. L. (2017). Longitudinal course of disaster-related PTSD among a prospective sample of adult Chilean natural disaster survivors. International Journal of Epidemiology, 46(2), 440–452. https://doi.org/10.1093/IJE/DYW094

• Galatzer-Levy, I. R., Nickerson, A., Litz, B. T., & Marmar, C. R. (2013). PATTERNS OF LIFETIME PTSD COMORBIDITY: A LATENT CLASS ANALYSIS. Depression and Anxiety, 30(5), 489–496. https://doi.org/10.1002/DA.22048

• Gallo, E. A. G., Munhoz, T. N., Loret de Mola, C., & Murray, J. (2018). Gender differences in the effects of childhood maltreatment on adult depression and anxiety: A systematic review and meta-analysis. Child Abuse & Neglect, 79, 107–114. https://doi.org/10.1016/J.CHIABU.2018.01.003

• Garfin, D. R., Silver, R. C., Ugalde, F. J., Linn, H., & Inostroza, M. (2014). Exposure to rapid succession disasters: A study of residents at the epicenter of the chilean Bío Bío earthquake. Journal of Abnormal Psychology, 123(3), 545–556. https://doi.org/10.1037/A0037374

• Hatori, T., & Bhandary, N. P. (2022). Posttraumatic stress disorder and its predictors in Kathmandu Valley residents after the 2015 Nepal Earthquake. International Journal of Disaster Risk Reduction, 69, 102733. https://doi.org/10.1016/J.IJDRR.2021.102733

• Hing, B., Sathyaputri, L., & Potash, J. B. (2018). A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 177(2), 143–167. https://doi.org/10.1002/ajmg.b.32616

• Hori, H., Itoh, M., Lin, M., Yoshida, F., Niwa, M., Hakamata, Y., Matsui, M., Kunugi, H., & Kim, Y. (2021). Childhood maltreatment history and attention bias variability in healthy adult women: role of inflammation and the BDNF Val66Met genotype. Translational Psychiatry 2021 11:1, 11(1), 1–12. https://doi.org/10.1038/s41398-021-01247-4

• Hori, H., Itoh, M., Yoshida, F., Lin, M., Niwa, M., Hakamata, Y., Ino, K., Imai, R., Ogawa, S., Matsui, M., Kamo, T., Kunugi, H., & Kim, Y. (2020). The BDNF Val66Met polymorphism affects negative memory bias in civilian women with PTSD. Scientific Reports 2020 10:1, 10(1), 1–8. https://doi.org/10.1038/s41598-020-60096-1

• Hughes, K., Bellis, M. A., Hardcastle, K. A., Sethi, D., Butchart, A., Mikton, C., Jones, L., & Dunne, M. P. (2017). The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. The Lancet Public Health, 2(8), e356–e366. https://doi.org/10.1016/S2468-2667(17)30118-4

• Kachadourian, L. K., Pilver, C. E., & Potenza, M. N. (2014). Trauma, PTSD, and binge and hazardous drinking among women and men: Findings from a national study. Journal of Psychiatric Research, 55(1), 35–43. https://doi.org/10.1016/J.JPSYCHIRES.2014.04.018

• Kane, J. C., Luitel, N. P., Jordans, M. J. D., Kohrt, B. A., Weissbecker, I., & Tol, W. A. (2018). Mental health and psychosocial problems in the aftermath of the Nepal earthquakes: findings from a representative cluster sample survey. Epidemiology and Psychiatric Sciences, 27(3), 301–310. https://doi.org/10.1017/S2045796016001104

• Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., & Aubry, J. M. (2002). Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Research, 109(2), 143–148. https://doi.org/10.1016/S0165-1781(02)00005-7

• Kessler, R. C., McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., Aguilar-Gaxiola, S., Alhamzawi, A. O., Alonso, J., Angermeyer, M., Benjet, C., Bromet, E., Chatterji, S., De Girolamo, G., Demyttenaere, K., Fayyad, J., Florescu, S., Gal, G., Gureje, O., … Williams, D. R. (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. The British Journal of Psychiatry : The Journal of Mental Science, 197(5), 378–385. https://doi.org/10.1192/BJP.BP.110.080499

• Kessler, R. C., & Üstün, B. B. (2004). The World Mental Health (WMH) Survey Initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). International Journal of Methods in Psychiatric Research, 13(2), 93–121. https://doi.org/10.1002/MPR.168

• King, M., Walker, C., Levy, G., Bottomley, C., Royston, P., Weich, S., Bellón-Saameño, J. Á., Moreno, B., Švab, I., Rotar, D., Rifel, J., Maaroos, H. I., Aluoja, A., Kalda, R., Neeleman, J., Geerlings, M. I., Xavier, M., Carraça, I., Gonçalves-Pereira, M., … Nazareth, I. (2008). Development and Validation of an International Risk Prediction Algorithm for Episodes of Major Depression in General Practice Attendees: The PredictD Study. Archives of General Psychiatry, 65(12), 1368–1376. https://doi.org/10.1001/ARCHPSYC.65.12.1368

• King, M., Weich, S., Torres-González, F., Švab, I., Maaroos, H.-I., Neeleman, J., Xavier, M., Morris, R., Walker, C., Bellón-Saameño, J. A., Moreno-Küstner, B., Rotar, D., Rifel, J., Aluoja, A., Kalda, R., Geerlings, M. I., Carraça, I., Almeida, M. C. de, Vicente, B., … Nazareth, I. (2006). Prediction of depression in European general practice attendees: the PREDICT study. BMC Public Health, 6, 6. https://doi.org/10.1186/1471-2458-6-6

• Larrañaga, O., & Herrera, R. (2010). Efectos en la calidad de vida de la población afectada por el terremoto/tsunami. Ministerio de Planificación. https://www.desarrollosocialyfamilia.gob.cl/pdf/informe-encuesta-post-terremoto.pdf

• Leiva-Bianchi, M., Baher, G., & Poblete, C. (2012). The Effects of Stress Coping Strategies in Post-Traumatic Stress Symptoms Among Earthquake Survivors: An Explanatory Model of Post-Traumatic Stress. Terapia Psicológica, 30(2), 51–59. https://doi.org/10.4067/S0718-48082012000200005

• Li, G., Wang, L., Cao, C., Fang, R., Hall, B. J., Elhai, J. D., & Liberzon, I. (2021a). Post-traumatic stress symptoms of children and adolescents exposed to the 2008 Wenchuan Earthquake: A longitudinal study of 5-HTTLPR genotype main effects and gene–environment interactions. International Journal of Psychology, 56(1), 22–29. https://doi.org/10.1002/IJOP.12614

• Li, G., Wang, L., Cao, C., Fang, R., Hall, B. J., Elhai, J. D., & Liberzon, I. (2021b). Post-traumatic stress symptoms of children and adolescents exposed to the 2008 Wenchuan Earthquake: A longitudinal study of 5-HTTLPR genotype main effects and gene–environment interactions. International Journal of Psychology, 56(1), 22–29. https://doi.org/10.1002/IJOP.12614

• Lommatzsch, M., Zingler, D., Schuhbaeck, K., Schloetcke, K., Zingler, C., Schuff-Werner, P., & Virchow, J. C. (2005). The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiology of Aging, 26(1), 115–123. https://doi.org/10.1016/j.neurobiolaging.2004.03.002

• Lonsdorf, T. B., Golkar, A., Lindström, K. M., Haaker, J., Öhman, A., Schalling, M., & Ingvar, M. (2015). BDNFval66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall. Social Cognitive and Affective Neuroscience, 10(5), 664–671. https://doi.org/10.1093/SCAN/NSU102

• Madsen, M. K., Mc Mahon, B., Andersen, S. B., Siebner, H. R., Knudsen, G. M., & Fisher, P. M. D. (2016). Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism. Social Cognitive and Affective Neuroscience, 11(1), 140–149. https://doi.org/10.1093/SCAN/NSV098

• Martinotti, G., Pettorruso, M., De Berardis, D., Varasano, P. A., Pressanti, G. L., De Remigis, V., Valchera, A., Ricci, V., Di Nicola, M., Janiri, L., Biggio, G., & Di Giannantonio, M. (2016). Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms. International Journal of Neuropsychopharmacology, 19(5), 1–6. https://doi.org/10.1093/IJNP/PYW003

• Maya-Mondragón, J., Sánchez-Román, F. R., Palma-Zarco, A., Aguilar-Soto, M., & Borja-Aburto, V. H. (2019). Prevalence of Post-traumatic Stress Disorder and Depression After the September 19th, 2017 Earthquake in Mexico. Archives of Medical Research, 50(8), 502–508. https://doi.org/10.1016/J.ARCMED.2019.11.008

• McLaughlin, K. A., Koenen, K. C., Bromet, E. J., Karam, E. G., Liu, H., Petukhova, M., Ruscio, A. M., Sampson, N. A., Stein, D. J., Aguilar-Gaxiola, S., Alonso, J., Borges, G., Demyttenaere, K., Dinolova, R. V., Ferry, F., Florescu, S., De Girolamo, G., Gureje, O., Kawakami, N., … Kessler, R. C. (2017). Childhood adversities and post-traumatic stress disorder: evidence for stress sensitisation in the World Mental Health Surveys. The British Journal of Psychiatry, 211(5), 280–288. https://doi.org/10.1192/BJP.BP.116.197640

• Mojtabavi, H., Saghazadeh, A., van den Heuvel, L., Bucker, J., & Rezaei, N. (2020). Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis. PLOS ONE, 15(11), e0241928. https://doi.org/10.1371/JOURNAL.PONE.0241928

• Molendijk, M. L., Bus, B. A. A., Spinhoven, P., Kaimatzoglou, A., Voshaar, R. C. O., Penninx, B. W. J. H., van Ijzendoorn, M. H., & Elzinga, B. M. (2012). A systematic review and meta-analysis on the association between BDNF val66met and hippocampal volume—A genuine effect or a winners curse? American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 159B(6), 731–740. https://doi.org/10.1002/AJMG.B.32078

• Molendijk, M. L., Bus, B. A. A., Spinhoven, P., Penninx, B. W. J. H., Kenis, G., Prickaerts, J., Voshaar, R. C. O., & Elzinga, B. M. (2011). Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. Molecular Psychiatry, 16(11), 1088–1095. https://doi.org/10.1038/MP.2010.98

• Monson, C. M., & Shnaider, P. (2014). Theory underlying trauma-focused interventions. Treating PTSD with Cognitive-Behavioral Therapies: Interventions That Work., 11–19. https://doi.org/10.1037/14372-002

• Nagahara, A. H., & Tuszynski, M. H. (2011). Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nature Reviews Drug Discovery, 10(3), 209–219. https://doi.org/10.1038/nrd3366

• Navarro-Mateu, F., Escámez, T., Koenen, K. C., Alonso, J., & Sánchez-Meca, J. (2013). Meta-Analyses of the 5-HTTLPR Polymorphisms and Post-Traumatic Stress Disorder. PLOS ONE, 8(6), e66227. https://doi.org/10.1371/JOURNAL.PONE.0066227

• Navarro-Mateu, F., Escámez, T., Quesada, M. P., Alcaráz, M. J., Vilagut, G., Salmerón, D., Huerta, J. M., Chirlaque, M. D., Navarro, C., Kessler, R. C., Alonso, J., & Martínez, S. (2019). Modification of the risk of post-traumatic stress disorder (PTSD) by the 5-HTTLPR polymorphisms after Lorca’s earthquakes (Murcia, Spain). Psychiatry Research, 282, 112640. https://doi.org/10.1016/J.PSYCHRES.2019.112640

• Ney, L. J., Matthews, A., Nicholson, E., Zuj, D., Ken Hsu, C. M., Steward, T., Graham, B., Harrison, B., Nichols, D., & Felmingham, K. (2021). BDNF genotype Val66Met interacts with acute plasma BDNF levels to predict fear extinction and recall. Behaviour Research and Therapy, 145, 103942. https://doi.org/10.1016/J.BRAT.2021.103942

• Norris, F., Galea, S., Friedman, M., & Watson, P. (2006). Methods for Disaster Mental Health Research.

• Notaras, M., Hill, R., & Van Den Buuse, M. (2015). The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy. Molecular Psychiatry, 20(8), 916–930. https://doi.org/10.1038/MP.2015.27

• Notaras, M., & van den Buuse, M. (2019). Brain-Derived Neurotrophic Factor (BDNF): Novel Insights into Regulation and Genetic Variation. The Neuroscientist : A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 25(5), 434–454. https://doi.org/10.1177/1073858418810142

• Notaras, M., & van den Buuse, M. (2020a). Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders. Molecular Psychiatry, 25(10), 2251–2274. https://doi.org/10.1038/s41380-019-0639-2

• Notaras, M., & van den Buuse, M. (2020b). Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders. Molecular Psychiatry 2020 25:10, 25(10), 2251–2274. https://doi.org/10.1038/s41380-019-0639-2

• Orsolini, L., Latini, R., Pompili, M., Serafini, G., Volpe, U., Vellante, F., Fornaro, M., Valchera, A., Tomasetti, C., Fraticelli, S., Alessandrini, M., La Rovere, R., Trotta, S., Martinotti, G., Di Giannantonio, M., & De Berardis, D. (2020). Understanding the Complex of Suicide in Depression: from Research to Clinics. Psychiatry Investigation, 17(3), 207–221. https://doi.org/10.30773/PI.2019.0171

• Ortega-Rojas, J., Arboleda-Bustos, C. E., Morales, L., Benítez, B. A., Beltrán, D., Izquierdo, Á., Arboleda, H., & Vásquez, R. (2017). Study of genetic variants in the BDNF, COMT, DAT1 and SERT genes in Colombian children with attention deficit disorder. Revista Colombiana de Psiquiatria, 46(4), 222–228. https://doi.org/10.1016/j.rcp.2016.08.006

• Pereira, M. A., Araújo, A., Simões, M., & Costa, C. (2022). Influence of Psychological Factors in Breast and Lung Cancer Risk – A Systematic Review. Frontiers in Psychology, 12, 5852. https://doi.org/10.3389/FPSYG.2021.769394/BIBTEX

• Pitts, B. L., Wen, V., Whealin, J. M., Fogle, B. M., Southwick, S. M., Esterlis, I., & Pietrzak, R. H. (2020). Depression and Cognitive Dysfunction in Older U.S. Military Veterans: Moderating Effects of BDNF Val66Met Polymorphism and Physical Exercise. Am J of Geriatric Psychiatry, 28(9), 959–967. https://doi.org/10.1016/j.jagp.2020.02.001

• Quinones, M. M., Gallegos, A. M., Lin, F. V., & Heffner, K. (2020). Dysregulation of inflammation, neurobiology, and cognitive function in PTSD: an integrative review. Cognitive, Affective, & Behavioral Neuroscience 2020 20:3, 20(3), 455–480. https://doi.org/10.3758/S13415-020-00782-9

• Ramirez, P., & Aliaga, J. (2012). Tsunami paso a paso: los escandalosos errores y omisiones del SHOA y la ONEMI - CIPER Chile. Ciper. https://www.ciperchile.cl/2012/01/18/tsunami-paso-a-paso-los-escandalosos-errores-y-omisiones-del-shoa-y-la-onemi/

• Robins, L. N., Wing, J., Wittchen, H. U., Helzer, J. E., Babor, T. F., Burke, J., Farmer, A., Jablenski, A., Pickens, R., Regier, D. A., Sartorius, N., & Towle, L. H. (1988). The Composite International Diagnostic Interview: An Epidemiologic Instrument Suitable for Use in Conjunction With Different Diagnostic Systems and in Different Cultures. Archives of General Psychiatry, 45(12), 1069–1077. https://doi.org/10.1001/ARCHPSYC.1988.01800360017003

• Rojas, R., Vicente, B., Saldivia, S., Melipillán, R., Aedo, G., Hormazabal, N., & Carroza, A. (2015). Asociación entre los polimorfismos 5HTTLPR, uMAOA y depresión en una cohorte de pacientes de atención primaria. Revista Médica de Chile, 143(10), 1252–1259. https://doi.org/10.4067/S0034-98872015001000003

• R-Project. (2023). R: The R Project for Statistical Computing. https://www.r-project.org/

• Santos, R., Bymes, B., & Lane, P. (2010). More than 2 million affected by earthquake, Chile’s president says - CNN.com. CNN World. http://edition.cnn.com/2010/WORLD/americas/02/27/chile.quake/

• Scott, K. M., Smith, D. R., & Ellis, P. M. (2010). Prospectively ascertained child maltreatment and its association with DSM-IV mental disorders in young adults. Archives of General Psychiatry, 67(7), 712–719. https://doi.org/10.1001/ARCHGENPSYCHIATRY.2010.71

• Stein, M. B., Chen, C. Y., Ursano, R. J., Cai, T., Gelernter, J., Heeringa, S. G., Jain, S., Jensen, K. P., Maihofer, A. X., Mitchell, C., Nievergelt, C. M., Nock, M. K., Neale, B. M., Polimanti, R., Ripke, S., Sun, X., Thomas, M. L., Wang, Q., Ware, E. B., … Zhang, L. (2016). Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers. JAMA Psychiatry, 73(7), 695–704. https://doi.org/10.1001/JAMAPSYCHIATRY.2016.0350

• Takei, S., Morinobu, S., Yamamoto, S., Fuchikami, M., Matsumoto, T., & Yamawaki, S. (2011). Enhanced hippocampal BDNF/TrkB signaling in response to fear conditioning in an animal model of posttraumatic stress disorder. Journal of Psychiatric Research, 45(4), 460–468. https://doi.org/10.1016/J.JPSYCHIRES.2010.08.009

• Tuerk, P. W., Wangelin, B., Rauch, S. A. M., Dismuke, C. E., Yoder, M., Myrick, H., Eftekhari, A., & Acierno, R. (2013). Health service utilization before and after evidence-based treatment for PTSD. Psychological Services, 10(4), 401–409. https://doi.org/10.1037/A0030549

• UNICEF. (2000). Maltrato Infantil en Chile. https://www.unicef.cl/archivos_documento/18/Cartilla Maltrato infantil.pdf

• Valente, N. L. M., Vallada, H., Cordeiro, Q., Miguita, K., Bressan, R. A., Andreoli, S. B., Mari, J. J., & Mello, M. F. (2011). Candidate-gene approach in posttraumatic stress disorder after urban violence: Association analysis of the genes encoding serotonin transporter, dopamine transporter, and BDNF. Journal of Molecular Neuroscience, 44(1), 59–67. https://doi.org/10.1007/S12031-011-9513-7/TABLES/6

• Vicente, B., Kohn, R., Rioseco, P., Saldivia, S., Levav, I., & Torres, S. (2006). Lifetime and 12-month prevalence of DSM-III-R disorders in the Chile psychiatric prevalence study. American Journal of Psychiatry, 163(8), 1362–1370. https://doi.org/10.1176/AJP.2006.163.8.1362/ASSET/IMAGES/LARGE/Q713T8.JPEG

• Vicente, B., Rojas, Romina., Sldivia, Sandra., Pérez, C., Melipillan, R., Hormazabal, N., & Phian, R. (2016). Determinantes biopsicosociales de depresión en pacientes atendidos en Centros de Atención Primaria de Concepción, Chile. Revista Chilena de Neuro-Psiquiatría, 54(2), 102–112. https://doi.org/10.4067/S0717-92272016000200004

• Wang, Q., Shelton, R. C., & Dwivedi, Y. (2018). Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis. Journal of Affective Disorders, 225, 422–428. https://doi.org/10.1016/J.JAD.2017.08.066

• Wang, T. (2015). Does BDNF Val66Met Polymorphism Confer Risk for Posttraumatic Stress Disorder? Neuropsychobiology, 71(3), 149–153. https://doi.org/10.1159/000381352

• Wendland, J. R., Martin, B. J., Kruse, M. R., Lesch, K. P., & Murphy, D. L. (2006). Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Molecular Psychiatry 2006 11:3, 11(3), 224–226. https://doi.org/10.1038/sj.mp.4001789

• WHO. (1997). Composite International Diagnostic Interview (CIDI, Version 2.1). World Health Organization. https://apps.who.int/iris/handle/10665/267892

• WHO Regional Committee for Europe. (2014). REGIONAL COMMITTEE FOR EUROPE 64th SESSION Regional Committee for Europe. Investing in Children: The European Child and Adolescent Health Strategy 2015–2020.

• Wolf, E. J., Maniates, H., Nugent, N., Maihofer, A. X., Armstrong, D., Ratanatharathorn, A., Ashley-Koch, A. E., Garrett, M., Kimbrel, N. A., Lori, A., VA Mid-Atlantic MIRECC Workgroup, Aiello, A. E., Baker, D. G., Beckham, J. C., Boks, M. P., Galea, S., Geuze, E., Hauser, M. A., Kessler, R. C., … Logue, M. W. (2018). Traumatic stress and accelerated DNA methylation age: A meta-analysis. Psychoneuroendocrinology, 92, 123–134. https://doi.org/10.1016/J.PSYNEUEN.2017.12.007

• Wolf, E. J., Miller, M. W., Sullivan, D. R., Amstadter, A. B., Mitchell, K. S., Goldberg, J., & Magruder, K. M. (2018). A classical twin study of PTSD symptoms and resilience: Evidence for a single spectrum of vulnerability to traumatic stress. Depression and Anxiety, 35(2), 132–139. https://doi.org/10.1002/DA.22712

• Xie, P., Kranzler, H. R., Poling, J., Stein, M. B., Anton, R. F., Brady, K., Weiss, R. D., Farrer, L., & Gelernter, J. (2009). Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations. Archives of General Psychiatry, 66(11), 1201–1209. https://doi.org/10.1001/ARCHGENPSYCHIATRY.2009.153

• Young, D. A., Chao, L. L., Zhang, H., Metzler, T., Ross, J., Richards, A., O’Donovan, A., Inslicht, S. S., & Neylan, T. C. (2021). Ventromedial and insular cortical volume moderates the relationship between BDNF Val66Met and threat sensitivity. Journal of Psychiatric Research, 142, 337–344. https://doi.org/10.1016/J.JPSYCHIRES.2021.08.012

• Zhang, K., Qu, S., Chang, S., Li, G., Cao, C., Fang, K., Olff, M., Wang, L., & Wang, J. (2017). An overview of posttraumatic stress disorder genetic studies by analyzing and integrating genetic data into genetic database PTSDgene. Neuroscience and Biobehavioral Reviews, 83, 647–656. https://doi.org/10.1016/J.NEUBIOREV.2017.08.021