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https://www.readbyqxmd.com/read/28215878/neuroactive-steroids-and-ptsd-treatment
#1
REVIEW
Ann M Rasmusson, Christine E Marx, Suzanne L Pineles, Andrea Locci, Erica R Scioli-Salter, Yael I Nillni, Jennifer J Liang, Graziano Pinna
This review highlights early efforts to translate pre-clinical and clinical findings regarding the role of neuroactive steroids in stress adaptation and PTSD into new therapeutics for PTSD. Numerous studies have demonstrated PTSD-related alterations in resting levels or the reactivity of neuroactive steroids and their targets. These studies also have demonstrated substantial variability in the dysfunction of specific neuroactive steroid systems among PTSD subpopulations. These variabilities have been related to the developmental timing of trauma, severity and type of trauma, genetic background, sex, reproductive state, lifestyle influences such as substance use and exercise, and the presence of comorbid conditions such as depression and chronic pain...
February 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28205604/selectively-bred-rats-provide-a-unique-model-of-vulnerability-to-ptsd-like-behavior-and-respond-differentially-to-fgf2-augmentation-early-in-life
#2
Katherine E Prater, Elyse L Aurbach, Hanna K Larcinese, Taylor N Smith, Cortney A Turner, Peter Blandino, Stanley J Watson, Stephen Maren, Huda Akil
Individuals respond differently to traumatic experiences including their propensity to develop post-traumatic stress disorder (PTSD). Understanding individual differences in PTSD vulnerability will allow the development of improved prevention and treatment options. Here, we characterized fear conditioning and extinction in rats selectively bred for differences in their locomotor response to a novel environment. Selectively bred high responder (bHR) and low responder (bLR) male rats are known to differ in their emotional reactivity on a range of measures of spontaneous anxiety- and depressive-like behaviors...
February 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28160694/genetic-and-serum-biomarker-evidence-for-a-relationship-between-tnf%C3%AE-and-ptsd-in-vietnam-war-combat-veterans
#3
Dagmar Bruenig, Divya Mehta, Charles P Morris, Wendy Harvey, Bruce Lawford, Ross McD Young, Joanne Voisey
BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with increased inflammation and comorbid medical conditions. However, study findings for individual inflammatory marker levels have been inconsistent. Some research suggests that resilience may play a role in decreased inflammation. A polymorphism in the promoter region of the tumor necrosis factor α gene (TNFα), TNFA -308 (rs1800629) is associated with psychiatric illness but its role in PTSD is yet to be elucidated. OBJECTIVE: This study investigates a key inflammatory marker, TNFα, for its role in PTSD severity...
January 24, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28143760/pretreatment-biomarkers-predicting-ptsd-psychotherapy-outcomes-a-systematic-review
#4
REVIEW
Peter J Colvonen, Lisa H Glassman, Laura D Crocker, Melissa M Buttner, Henry Orff, Dawn M Schiehser, Sonya B Norman, Niloofar Afari
Although our understanding of the relationship between posttraumatic stress disorder (PTSD), brain structure and function, neural networks, stress-related systems, and genetics is growing, there is considerably less attention given to which biological markers predict evidence-based PTSD psychotherapy outcomes. Our systematic PRISMA-informed review of 20 studies examined biomarkers as predictors of evidence-based PTSD psychotherapy outcomes. Results provide preliminary evidence that specific structural and functional neural systems (involved in information processing), glucocorticoid sensitivity and metabolism (part of the hypothalamic-pituitary-adrenal axis and the response to stress), heart rate (involved with fear habituation), gene methylation, and certain genotypes (associated with serotonin and glucocorticoids) predicted positive response to PTSD treatment...
January 28, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28115477/a-deletion-variant-of-the-%C3%AE-2b-adrenoceptor-modulates-the-stress-induced-shift-from-cognitive-to-habit-memory
#5
Lisa Wirz, Jan Wacker, Andrea Felten, Martin Reuter, Lars Schwabe
: Stress induces a shift from hippocampus-based 'cognitive' towards dorsal striatum-based 'habitual' learning and memory. This shift is thought to have important implications for stress-related psychopathologies, including posttraumatic stress disorder (PTSD). However, there is large individual variability in the stress-induced bias towards habit memory and the factors underlying this variability are completely unknown. Here we hypothesized that a functional deletion variant of the gene encoding the α2b-adrenoceptor (ADRA2B), which has been linked to emotional memory processes and increased PTSD risk, modulates the stress-induced shift from cognitive towards habit memory...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28097489/enhanced-histone-acetylation-in-the-infralimbic-prefrontal-cortex-is-associated-with-fear-extinction
#6
Sarfraj Ahmad Siddiqui, Sanjay Singh, Vandana Ranjan, Rajesh Ugale, Sudipta Saha, Anand Prakash
The molecular processes that establish fear memory are complex and involve a combination of genetic and epigenetic influences. Dysregulation of these processes can manifest in humans as a range of fear-related anxiety disorders like post-traumatic stress disorders (PTSD). In the present study, immunohistochemistry for acetyl H3, H4, c-fos, CBP (CREB-binding protein) in the infralimbic prefrontal cortex (IL-PFC) and prelimbic prefrontal cortex (PL-PFC) of mPFC (medial prefrontal cortex) and basal amygdala (BA), lateral amygdala (LA), centrolateral amygdala (CeL), centromedial amygdala (CeM) of the amygdala was performed to link region-specific histone acetylation to fear and extinction learning...
January 17, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28067785/relationships-between-gat1-and-ptsd-depression-and-substance-use-disorder
#7
Kaitlin E Bountress, Wei Wei, Christina Sheerin, Dongjun Chung, Ananda B Amstadter, Howard Mandel, Zhewu Wang
Post-traumatic stress disorder (PTSD), Major Depressive Disorder (MDD), and Substance Use Disorder (SUD) have large public health impacts. Therefore, researchers have attempted to identify those at greatest risk for these phenotypes. PTSD, MDD, and SUD are in part genetically influenced. Additionally, genes in the glutamate and gamma-aminobutyric acid (GABA) system are implicated in the encoding of emotional and fear memories, and thus may impact these phenotypes. The current study examined the associations of single nucleotide polymorphisms in GAT1 individually, and at the gene level, using a principal components (PC) approach, with PTSD, PTSD comorbid with MDD, and PTSD comorbid with SUD in 486 combat-exposed veterans...
January 5, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28030471/stress-related-psychological-symptoms-contribute-to-axial-pain-persistence-after-motor-vehicle-collision-path-analysis-results-from-a-prospective-longitudinal-study
#8
Rose K Feinberg, June Hu, Mark A Weaver, Roger B Fillingim, Robert A Swor, David A Peak, Jeffrey S Jones, Niels K Rathlev, David C Lee, Robert M Domeier, Phyllis L Hendry, Israel Liberzon, Samuel A McLean
Post-traumatic stress disorder (PTSD) symptoms and pain after traumatic events such as motor vehicle collision (MVC) have been proposed to be mutually promoting. We performed a prospective multicenter study that enrolled 948 individuals who presented to the emergency department (ED) within 24 hours of MVC and were discharged home after evaluation. Follow-up evaluations were completed 6 weeks, 6 months, and 1 year after MVC. Path analysis results supported the hypothesis that axial pain after MVC consistently promotes the maintenance of hyperarousal and intrusive symptoms, from the early weeks post-injury through 1 year...
December 22, 2016: Pain
https://www.readbyqxmd.com/read/28025095/a-cross-species-study-of-heterogeneity-in-fear-extinction-learning-in-relation-to-fkbp5-variation-and-expression-implications-for-the-acute-treatment-of-posttraumatic-stress-disorder
#9
Isaac R Galatzer-Levy, Raül Andero, Takehito Sawamura, Tanja Jovanovic, Santiago Papini, Kerry J Ressler, Seth Davin Norrholm
Deficits in fear extinction learning are hypothesized to underlie the development of posttraumatic stress disorder (PTSD). Such deficits may, in part, be due to genetic and epigenetic variation in the stress related gene FKBP5. Conversely, altering FKBP5 epigenetic responses during memory consolidation may rescue extinction deficits making it a target for acute intervention to prevent the development of PTSD. Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re-experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM)...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27959335/functional-evaluation-of-a-ptsd-associated-genetic-variant-estradiol-regulation-and-adcyap1r1
#10
K B Mercer, B Dias, D Shafer, S A Maddox, J G Mulle, P Hu, J Walton, K J Ressler
Posttraumatic stress disorder (PTSD) affects 5-10% percent of the US adult population with a higher prevalence among women compared with men. Although it remains unclear how biological sex associates with susceptibility to PTSD, one mechanism may involve a role for estrogen in a gene by environment interaction. We previously demonstrated a sex-dependent association between the pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) and PTSD, where carriers of a C allele at single-nucleotide polymorphism (SNP) rs2267735 within the PAC1 receptor gene (ADCYAP1R1) have increased symptoms of PTSD...
December 13, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27933312/the-genetics-and-epigenetics-of-ptsd-overview-recent-advances-and-future-directions
#11
Christina M Sheerin, Mackenzie J Lind, Kaitlin Bountress, Nicole R Nugent, Ananda B Amstadter
This paper provides a brief summary and commentary on the growing literature and current developments related to the genetic underpinnings of posttraumatic stress disorder (PTSD). We first briefly provide an overview of the behavioral genetic literature on PTSD, followed by a short synopsis of the substantial candidate gene literature with a focus on genes that have been meta-analyzed. We then discuss the genome-wide association studies (GWAS) that have been conducted, followed by an introduction to other molecular platforms used in PTSD genomic studies, such as epigenetic and expression approaches...
April 2017: Current Opinion in Psychology
https://www.readbyqxmd.com/read/27908524/genetic-correlation-between-alcohol-preference-and-conditioned-fear-exploring-a-functional-relationship
#12
Julia A Chester, Marcus M Weera
Post-traumatic stress disorder (PTSD) and alcohol-use disorders have a high rate of co-occurrence, possibly because they are regulated by common genes. In support of this idea, mice selectively bred for high (HAP) alcohol preference show greater fear potentiated startle (FPS), a model for fear-related disorders such as PTSD, compared to mice selectively bred for low (LAP) alcohol preference. This positive genetic correlation between alcohol preference and FPS behavior suggests that the two traits may be functionally related...
February 2017: Alcohol
https://www.readbyqxmd.com/read/27863803/research-domain-criteria-and-the-study-of-trauma-in-children-implications-for-assessment-and-treatment-research
#13
REVIEW
Carla Smith Stover, Brooks Keeshin
By definition, the Diagnostic and Statistical Manual (DSM) diagnosis of posttraumatic stress disorder (PTSD) requires exposure to a traumatic event. Yet, the DSM diagnostic requirements for children and adolescents for PTSD may fail to capture traumatized youth with significant distress and functional impairment. Many important studies have utilized PTSD diagnosis as a mechanism for grouping individuals for comparative studies examining brain functioning, neuroendocrinology, genetics, attachment, and cognition; however, focusing only on those with the diagnosis of PTSD can miss the spectrum of symptoms and difficulties that impact children who experience trauma and subsequent impairment...
November 9, 2016: Clinical Psychology Review
https://www.readbyqxmd.com/read/27845777/newer-insights-into-the-role-of-mirna-a-tiny-genetic-tool-in-psychiatric-disorders-focus-on-post-traumatic-stress-disorder
#14
REVIEW
V V Giridharan, R A Thandavarayan, G R Fries, C Walss-Bass, T Barichello, N J Justice, M K Reddy, J Quevedo
Post-traumatic stress disorder (PTSD) is a mental disorder occurring in about 2-9% of individuals after their exposure to life-threatening events, such as severe accidents, sexual abuse, combat or a natural catastrophe. Because PTSD patients are exposed to trauma, it is likely that epigenetic modifications have an important role in disease development and prognosis. For the past two decades, abnormal expression of the epigenetic regulators microRNAs (miRs) and miR-mediated gene regulation have been given importance in a variety of human diseases, such as cancer, heart disease and viral infection...
November 15, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27834145/pharmacogenetics-and-pharmacotherapy-of-military-personnel-suffering-from-posttraumatic-stress-disorder
#15
Janine Naß, Thomas Efferth
BACKGROUND: Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combat experience and still difficult to treat. The pathogenesis is still not fully understood at the psychological level. Therefore, genetic research became a focus of interest. The identification of single nucleotide polymorphisms (SNPs) may help to predict, which persons are at high risk to develop PTSD as a starting point to develop novel targeted drugs for treatment. METHODS: We conducted a systematic review on SNPs in genes related to PTSD pathology and development of targeted pharmacological treatment options based on PubMed database searches...
November 11, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27794503/modifiable-risk-factors-for-chronic-back-pain-insights-using-the-co-twin-control-design
#16
Pradeep Suri, Edward J Boyko, Nicholas L Smith, Jeffrey G Jarvik, Frances M K Williams, Gail P Jarvik, Jack Goldberg
BACKGROUND: Inconsistent associations between modifiable risk factors and chronic back pain (CBP) may be due to the inability of traditional epidemiologic study designs to properly account for an array of potential genetic and environmental confounding factors. The co-twin control research design, comparing modifiable risk factors in twins discordant for CBP, offers a unique way to remove numerous confounding factors. PURPOSE: The study aimed to examine the association of modifiable lifestyle and psychological factors with lifetime CBP...
January 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/27775175/genetic-risk-mechanisms-of-posttraumatic-stress-disorder-in-the-human-brain
#17
Rahul A Bharadwaj, Andrew E Jaffe, Qiang Chen, Amy Deep-Soboslay, Aaron L Goldman, Michelle I Mighdoll, John A Cotoia, Anna C Brandtjen, JooHeon Shin, Thomas M Hyde, Venkata S Mattay, Daniel R Weinberger, Joel E Kleinman
Posttraumatic stress disorder (PTSD) follows exposure to a traumatic event in susceptible individuals. Recently, genome-wide association studies have identified a number of genetic sequence variants that are associated with the risk of developing PTSD. To follow up on identifying the molecular mechanisms of these risk variants, we performed genotype to RNA sequencing-derived quantitative expression (whole gene, exon, and exon junction levels) analysis in the dorsolateral prefrontal cortex (DLPFC) of normal postmortem human brains...
October 24, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27769642/comt-val-158-met-polymorphism-is-associated-with-post-traumatic-stress-disorder-and-functional-outcome-following-mild-traumatic-brain-injury
#18
MULTICENTER STUDY
Ethan A Winkler, John K Yue, Adam R Ferguson, Nancy R Temkin, Murray B Stein, Jason Barber, Esther L Yuh, Sourabh Sharma, Gabriela G Satris, Thomas W McAllister, Jonathan Rosand, Marco D Sorani, Hester F Lingsma, Phiroz E Tarapore, Esteban G Burchard, Donglei Hu, Celeste Eng, Kevin K W Wang, Pratik Mukherjee, David O Okonkwo, Ramon Diaz-Arrastia, Geoffrey T Manley
Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val(158)Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively...
January 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27729874/dopamine-rebound-excitation-theory-putting-brakes-on-ptsd
#19
Jason C Lee, Lei Philip Wang, Joe Z Tsien
It is not uncommon for humans or animals to experience traumatic events in their lifetimes. However, the majority of individuals are resilient to long-term detrimental changes turning into anxiety and depression, such as post-traumatic stress disorder (PTSD). What underlying neural mechanism accounts for individual variability in stress resilience? Hyperactivity in fear circuits, such as the amygdalar system, is well-known to be the major pathophysiological basis for PTSD, much like a "stuck accelerator." Interestingly, increasing evidence demonstrates that dopamine (DA) - traditionally known for its role in motivation, reward prediction, and addiction - is also crucial in regulating fear learning and anxiety...
2016: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/27721742/-soldier-s-heart-a-genetic-basis-for-elevated-cardiovascular-disease-risk-associated-with-post-traumatic-stress-disorder
#20
Harvey B Pollard, Chittari Shivakumar, Joshua Starr, Ofer Eidelman, David M Jacobowitz, Clifton L Dalgard, Meera Srivastava, Matthew D Wilkerson, Murray B Stein, Robert J Ursano
"Soldier's Heart," is an American Civil War term linking post-traumatic stress disorder (PTSD) with increased propensity for cardiovascular disease (CVD). We have hypothesized that there might be a quantifiable genetic basis for this linkage. To test this hypothesis we identified a comprehensive set of candidate risk genes for PTSD, and tested whether any were also independent risk genes for CVD. A functional analysis algorithm was used to identify associated signaling networks. We identified 106 PTSD studies that report one or more polymorphic variants in 87 candidate genes in 83,463 subjects and controls...
2016: Frontiers in Molecular Neuroscience
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