Benjamin Suarez-Jimenez1,2, Anton Albajes-Eizagirre3, Amit Lazarov1,2,4, Xi Zhu1,2, Ben J Harrison5, Joaquim Radua3,6,7,8, Yuval Neria1,2, Miquel A Fullana3,9. 1. Department of Psychiatry, Columbia University Medical Center, New York, USA. 2. New York State Psychiatric Institute, New York, USA. 3. FIDMAG Germanes Hospitalàries, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain. 4. School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel. 5. Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Victoria, Australia. 6. Institute of Psychiatry, King's College London, De Crespigny Park, London, UK. 7. Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden. 8. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain. 9. Department of Psychiatry, Universitat Autònoma de Barcelona, Barcelona, Spain.
Abstract
BACKGROUND: Establishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers. METHODS: Here, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-based d-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall. RESULTS: Patients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis. CONCLUSION: Findings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.
BACKGROUND: Establishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers. METHODS: Here, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-based d-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall. RESULTS:Patients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis. CONCLUSION: Findings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.
Authors: Allison M Letkiewicz; Amy L Cochran; Anthony A Privratsky; G Andrew James; Josh M Cisler Journal: Cogn Affect Behav Neurosci Date: 2021-08-26 Impact factor: 3.526
Authors: G Kastrati; J Rosén; M Fredrikson; X Chen; R Kuja-Halkola; H Larsson; K B Jensen; F Åhs Journal: Transl Psychiatry Date: 2022-03-08 Impact factor: 7.989