title: Intensified vmPFC surveillance over PTSS under perturbed microRNA-608/AChE interaction.
abstract: Trauma causes variable risk of posttraumatic stress symptoms (PTSS) owing to yet-unknown genome-neuronal interactions. Here, we report co-intensified amygdala and ventromedial prefrontal cortex (vmPFC) emotional responses that may overcome PTSS in individuals with the single-nucleotide polymorphism (SNP) rs17228616 in the acetylcholinesterase (AChE) gene. We have recently shown that in individuals with the minor rs17228616 allele, this SNP interrupts AChE suppression by microRNA (miRNA)-608, leading to cortical elevation of brain AChE and reduced cortisol and the miRNA-608 target GABAergic modulator CDC42, all stress-associated. To examine whether this SNP has effects on PTSS and threat-related brain circuits, we exposed 76 healthy Israel Defense Forces soldiers who experienced chronic military stress to a functional magnetic resonance imaging task of emotional and neutral visual stimuli. Minor allele individuals predictably reacted to emotional stimuli by hyperactivated amygdala, a hallmark of PTSS and a predisposing factor of posttraumatic stress disorder (PTSD). Despite this, minor allele individuals showed no difference in PTSS levels. Mediation analyses indicated that the potentiated amygdala reactivity in minor allele soldiers promoted enhanced vmPFC recruitment that was associated with their limited PTSS. Furthermore, we found interrelated expression levels of several miRNA-608 targets including CD44, CDC42 and interleukin 6 in human amygdala samples (N=7). Our findings suggest that miRNA-608/AChE interaction is involved in the threat circuitry and PTSS and support a model where greater vmPFC regulatory activity compensates for amygdala hyperactivation in minor allele individuals to neutralize their PTSS susceptibility.
authors.affiliation: The Tel-Aviv Center for Brain Function, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Lin
authors.affiliation: The Edmond and Lily Safra Center for Brain Science, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Simchovitz
authors.affiliation: The Edmond and Lily Safra Center for Brain Science, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Shenhar-Tsarfaty
authors.affiliation: The Tel-Aviv Center for Brain Function, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Vaisvaser
authors.affiliation: The Tel-Aviv Center for Brain Function, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Admon
authors.affiliation: The Edmond and Lily Safra Center for Brain Science, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Hanin
authors.affiliation: The Edmond and Lily Safra Center for Brain Science, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Hanan
authors.affiliation: The Tel-Aviv Center for Brain Function, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Kliper
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Bar-Haim
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Shomron
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department for Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Fernandez
authors.affiliation: Division of Mental Health, Medical Corps, Israel Defense Forces, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Lubin
authors.affiliation: Division of Mental Health, Medical Corps, Israel Defense Forces, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Fruchter
authors.affiliation: The Tel-Aviv Center for Brain Function, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.|Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Hendler
authors.affiliation: The Edmond and Lily Safra Center for Brain Science, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001931:Brain Mapping / Q000379:methods; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D006801:Humans; D007557:Israel; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008889:Military Personnel; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000503:physiopathology*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D058851:GPI-Linked Proteins; D035683:MicroRNAs; C548244:ACHE protein, human; D000110:Acetylcholinesterase