Posttraumatic stress disorder and neuroprogression: new approaches to understand the effects of violence on mental functioning

• Grant number: 14/12559-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2015
• End date: April 30, 2022
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Marcelo Feijó de Mello
• Grantee: Marcelo Feijó de Mello
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais:( Últimos ): Andrea de Abreu Feijó de Mello ; Andrea Parolin Jackowski ; Dalva Lucia Rollemberg Poyares ; Mario Francisco Pereira Juruena
• Pesquisadores principais:( Antigos ): Síntia Iole Nogueira Belangero
• Associated researchers: Andrea de Abreu Feijó de Mello ; Andrea Parolin Jackowski ; João Ricardo Sato
• Associated research grant(s): 18/22224-1 - The impact of maternal exposure to childhood adversities on infant brain development, AP.R SPRINT
• Associated scholarship(s): 20/14814-3 - Pharmacological treatment of Post-traumatic Stress Disorder: a systematic literature review, BP.IC; 20/12990-9 - Attrition rates in women with Posttraumatic Stress Disorder (PTSD) after rape: a systematic literature review and qualitative evaluation of treatment discontinuation with patients from the Thematic Project, BP.IC; 19/13417-3 - Evaluation of vulnerable women due to the altered state of consciousness induced by substances and lack of consent for sexual meeting as risk factors of gravity of TEPT triggered by rape , BP.IC; + associated scholarships 19/12629-7 - Body-mass index and abdominal circumference in young patients with posttraumatic stress disorder after sexual assault, BP.IC; 16/22584-2 - Post traumatic stress disorder in raped victims: applicability of interpersonal psychotherapy, BP.MS; 17/03600-0 - Influence of early-life stress on feeding and psychiatric profile of atypical depressed patients, BP.IC; 15/26473-8 - Search for genetic, epigenetic and molecular markers of post-traumatic stress disorder, BP.DR; 15/18773-1 - Translational evaluation of the Hypothalamus-Pituitary-Adrenal axis and the early life stress-induced allostatic load roles on neuroprogression and vulnerability to psychopathologies, BP.PD; 15/06303-0 - Psychotherapy in the treatment of chronic Posttraumatic Stress Disorder in a violence research and treatment service, BP.IC - associated scholarships

Abstract

Posttraumatic stress disorder is triggered by an external event that threatening individual physical integrity, leading to characteristics symptoms of reviviscence, avoidance/numbing and hyperarousal. Despite the external adverse event, some predisposing factors are present presupposing multicausality. Once PTSD is installed, it has chronic features leading to important functional impairment. Many biological dysfunctions have been described associated with PTSD, including an altered stress response system suggesting a corresponding increase allostatic load. We hypothesized that this increased allostatic load will lead to neurodegeneration that we will call neuroprogression. We propose to evaluate if there are a correspondence between clinical and neurobiological functioning associated to disease progression. We will evaluate and follow-up 120 outpatients with PTSD triggered by sexual abuse. We choose the event as it is often at our city, and as it is a high risk factor for PTSD development. We will have also a control group with 120 subjects without history of trauma or abuse and without psychiatric diagnostic paired by gender and age. Subjects will be evaluate at inclusion related to sociodemographic data, diagnostic, history of child maltreatment, for symptoms severity, functioning and quality of life, also they will classified by time-interval between trauma and symptoms onset until their firs evaluation for the present study. All patients will receive standard treatment for PTSD according to violence program guideline. Many evaluations will be executed including biological markers as: genetics, biochemical, molecular and image. Neuropsychological data and sleep evaluation will be performed, at inclusion and at each six months during one-year period. Patients will be enrolled on a head-to-head randomized controlled clinical trial to compare efficacy of two treatments known as effective in PTSD: fluoxetine Interpersonal therapy (IPT) during 12-weeks. Non responders will enrolled on a cross-over second phase, when those on IPT will receive fluoxetine, and those receiving medication will receive IPT. Crossing response and remission data with biomarker could be useful as predictive biomarkers of therapeutic response. (AU)

Scientific publications

(22)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

YEH, MARY S. L.; POYARES, DALVA; COIMBRA, BRUNO MESSINA; MELLO, ANDREA FEIJO; TUFIK, SERGIO; MELLO, MARCELO FEIJO. Subjective and objective sleep quality in young women with posttraumatic stress disorder following sexual assault: a prospective study. EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY, v. 12, n. 1, JAN 1 2021. (14/12559-5)

XAVIER, GABRIELA; SPINDOLA, LETICIA M.; OTA, VANESSA K.; CARVALHO, CAROLINA M.; MAURYA, PAWAN KUMAR; TEMPAKU, PRISCILA F.; MORETTI, PATRICIA N.; MAZOTTI, DIEGO R.; SATO, JOAO RICARDO; BRIETZKE, ELISA; et al. Effect of male-specific childhood trauma on telomere length. JOURNAL OF PSYCHIATRIC RESEARCH, v. 107, p. 104-109, DEC 2018. (16/19462-2, 11/50740-5, 14/12559-5)

OLIVEIRA-WATANABE, THAUANA T.; RAMOS-LIMA, LUIS F.; SANTOS, ROBERTA C.; MELLO, MARCELO F.; MELLO, ANDREA F.. The Clinician-Administered PTSD Scale (CAPS-5): adaptation to Brazilian Portuguese. Revista Brasileira de Psiquiatria, v. 41, n. 1, p. 92-93, JAN-MAR 2019. (14/12559-5)

CARVALHO, CAROLINA M.; COIMBRA, BRUNO M.; OTA, VANESSA K.; MELLO, MARCELO F.; BELANGERO, SINTIA I.. Single-nucleotide polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis as risk factors for posttraumatic stress disorder. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, v. 174, n. 7, p. 671-682, OCT 2017. (14/12559-5)

PROENCA, CECILIA R.; MARKOWITZ, JOHN C.; PRADO, EUTHYMIA A.; BRAGA, ROSALY; COIMBRA, BRUNO M.; MELLO, THAYS F.; MACIEL, MARIANA R.; PUPO, MARIANA; POVOA, JULIANA; MELLO, ANDREA F.; et al. Attrition in Interpersonal Psychotherapy Among Women With Post-traumatic Stress Disorder Following Sexual Assault. FRONTIERS IN PSYCHOLOGY, v. 10, SEP 13 2019. (14/12559-5, 16/22584-2)

ZYLBERSTAJN, CECILIA; COIMBRA, BRUNO MESSINA; OLIVEIRA-WATANABE, THAUANA T.; MACIEL, MARIANA RANGEL; CALSAVARA, VINICIUS F.; OLFF, MIRANDA; MELLO, MARCELO FEIJO; MELLO, ANDREA FEIJO. The relationship between lifetime exposure to potentially traumatic events, peritraumatic dissociation, and PTSD in a sample of sexually assaulted women in Sao Paulo, Brazil. JOURNAL OF TRAUMA & DISSOCIATION, v. N/A, p. 16-pg., 2022-10-23. (14/12559-5)

PROENCA, CECILIA R.; MARKOWITZ, JOHN C.; COIMBRA, BRUNO M.; COGO-MOREIRA, HUGO; MACIEL, MARIANA R.; MELLO, ANDREA F.; MELLO, MARCELO F.. Interpersonal psychotherapy versus sertraline for women with posttraumatic stress disorder following recent sexual assault: a randomized clinical trial. EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY, v. 13, n. 2, p. 14-pg., 2022-12-19. (14/12559-5)

YEH, MARY S. L.; POYARES, DALVA; COIMBRA, BRUNO MESSINA; MELLO, ANDREA FEIJO; TUFIK, SERGIO; MELLO, MARCELO FEIJO. Subjective and objective sleep quality in young women with posttraumatic stress disorder following sexual assault: a prospective study. EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY, v. 12, n. 1, p. 12-pg., 2021-01-01. (14/12559-5)

CIVIDANES, GIULIANA C.; MELLO, ANDREA F.; MELLO, MARCELO F.. Revictimization as a high-risk factor for development of posttraumatic stress disorder: a systematic review of the literature. Revista Brasileira de Psiquiatria, v. 41, n. 1, p. 82-89, JAN-MAR 2019. (14/12559-5)

D'ELIA, ANA T. D.; MATSUZAKA, CAMILA T.; NETO, JAIR B. B.; MELLO, MARCELO F.; JURUENA, MARIO F.; MELLO, ANDREA F.. Childhood Sexual Abuse and Indicators of Immune Activity: A Systematic Review. FRONTIERS IN PSYCHIATRY, v. 9, AUG 6 2018. (14/12559-5)

OLIVEIRA-WATANABE, THAUANA TORRES; RAMOS-LIMA, LUIS FRANCISCO; ZYLBERSTAJN, CECILIA; CALSAVARA, VINICIUS; COIMBRA, BRUNO MESSINA; MACIEL, MARIANA RANGEL; FREITAS, LUCIA HELENA MACHADO; MELLO, MARCELO FEIJO; MELLO, ANDREA FEIJO. Validation of the Brazilian-Portuguese Version of the Clinician Administered Post Traumatic Stress Disorder Scale-5. FRONTIERS IN PSYCHIATRY, v. 12, JUN 22 2021. (14/12559-5)

COIMBRA, BRUNO MESSINA; YEH, MARY; D'ELIA, ANA TERESA; MACIEL, MARIANA RANGEL; CARVALHO, CAROLINA MUNIZ; MILANI, ANA CAROLINA; MOZZAMBANI, ADRIANA; JURUENA, MARIO; BELANGERO, SINTIA IOLE; JACKOWSKI, ANDREA PAROLIN; et al. Posttraumatic Stress Disorder and Neuroprogression in Women Following Sexual Assault: Protocol for a Randomized Clinical Trial Evaluating Allostatic Load and Aging Process Acceleration. JMIR RESEARCH PROTOCOLS, v. 9, n. 11, NOV 2020. (14/12559-5, 15/26473-8)

COIMBRA, BRUNO MESSINA; CARVALHO, CAROLINA MUNIZ; MORETTI, PATRICIA NATALIA; MELLO, MARCELO FEIJO; BELANGERO, SINTIA I.. Stress-related telomere length in children: A systematic review. JOURNAL OF PSYCHIATRIC RESEARCH, v. 92, p. 47-54, SEP 2017. (14/07280-1, 14/12559-5)

COIMBRA, BRUNO MESSINA; CARVALHO, CAROLINA MUNIZ; VAN ZUIDEN, MIRJAM; WILLIAMSON, RACHEL E.; OTA, VANESSA KIYOMI; MELLO, ANDREA FEIJO; BELANGERO, SINTIA IOLE; OLFF, MIRANDA; MELLO, MARCELO FEIJO. The impact of neighborhood context on telomere length: A systematic review. HEALTH & PLACE, v. 74, p. 11-pg., 2022-03-01. (14/12559-5)

D'ELIA, ANA TERESA D.; JURUENA, MARIO F.; COIMBRA, BRUNO M.; MELLO, MARCELO F.; MELLO, ANDREA F.. Posttraumatic stress disorder (PTSD) and depression severity in sexually assaulted women: hypothalamic-pituitary-adrenal (HPA) axis alterations. BMC Psychiatry, v. 21, n. 1, MAR 31 2021. (14/12559-5)

COIMBRA, BRUNO MESSINA; CARVALHO, CAROLINA MUNIZ; OTA, VANESSA KIYOMI; VIEIRA-FONSECA, TAMIRIS; BUGIGA, AMANDA; MELLO, ANDREA FEIJO; MELLO, MARCELO FEIJO; BELANGERO, SINTIA IOLE. A systematic review on the effects of social discrimination on telomere length. PSYCHONEUROENDOCRINOLOGY, v. 120, p. 8-pg., 2020-10-01. (14/12559-5)

MENEZES, ITIANA CASTRO; VON WERNE BAES, CRISTIANE; FIGARO-DRUMOND, FERNANDA VIANA; DIAS MACEDO, BRISA BURGOS; BUENO, ANA CAROLINA; LACCHINI, RICCARDO; FEIJO DE MELLO, MARCELO; DE CASTRO, MARGARET; JURUENA, MARIO FRANCISCO. Differential Diagnosis of Major Depressive Disorder and Bipolar Disorder: Genetic and Hormonal Assessment and the Influence of Early-Life Stress. BRAIN SCIENCES, v. 12, n. 11, p. 21-pg., 2022-11-01. (14/12559-5)

SUSSMAN, TAMARA J.; POSNER, JONATHAN; JACKOWSKI, ANDREA PAROLIN; CORREA, ADRIANA; HOFFMANN, ELLIS VIVIANE; PERUZZI, FERNANDA PORTO DE OLIVEIRA; GRECCO, FERNANDO RODRGUES; NITZSCHE, SAMARA HIPOLITO; MESQUITA, MARIA ENGENIA; FOESTER, BERND UWE; et al. The relationship between recent PTSD secondary to sexual assault, hippocampal volume and resting state functional connectivity in adolescent girls. NEUROBIOLOGY OF STRESS, v. 17, p. 10-pg., 2022-03-01. (14/12559-5)

DEMELLO, RICARDO A. F.; COIMBRA, BRUNO MESSINA; PEDRO, BIANCA D. M.; BENVENUTTI, ISABELLA M.; YEH, MARY S. L.; MELLO, ANDREA F.; MELLO, MARCELO F.; POYARES, DALVA R.. Peri-Traumatic Dissociation and Tonic Immobility as Severity Predictors of Posttraumatic Stress Disorder After Rape. JOURNAL OF INTERPERSONAL VIOLENCE, v. N/A, p. 27-pg., 2022-07-28. (14/12559-5)

FATURI, CLAUDIA; FURTADO, GEIELLE; MOTA-ORTIZ, SANDRA; MELLO, MARCELO. Fear Extinction of Predatory Threat as an Animal Model of Posttraumatic Stress Disorder (PTSD). BIOLOGICAL PSYCHIATRY, v. 81, n. 10, p. 1-pg., 2017-05-15. (14/12559-5)

SUSSMAN, TAMARA; POSNER, JONATHAN; JACKOWSKI, ANDREA PAROLIN; CORREA, ADRIANA; FOERSTER, BERND UWE; NITZSCHE, SAMARA HIPOLITO; MESQUITA, MARIA EUGENIA; MELLO, MARCELO FEIJO; MILANI, ANA CAROLINA. PTSD- and IPT-Related Differences in Intrinsic Connectivity in a Pilot Sample of Female Adolescent Survivors of Sexual Assault With PTSD. NEUROPSYCHOPHARMACOLOGY, v. 44, n. SUPPL 1, p. 2-pg., 2019-12-01. (14/12559-5)

CIVIDANES, GIULIANA C.; MELLO, ANDREA F.; MELLO, MARCELO F.. Revictimization as a high-risk factor for development of posttraumatic stress disorder: a systematic review of the literature. Revista Brasileira de Psiquiatria, v. 41, n. 1, p. 8-pg., 2019-01-01. (14/12559-5)