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Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats.

ABSTRACT: BACKGROUND:Traumatic experience can result in life-long changes in the ability to cope with future stressors and emotionally salient events. These experiences, particularly during early development, are a significant risk factor for later life anxiety disorders such as posttraumatic stress disorder (PTSD). However, because traumatic experience typically results in strong episodic memories, it is not known whether such long-term memories are necessary for particular features of PTSD, such as enhanced fear and anxiety. Here, we used a fear conditioning procedure in juvenile rats before maturation of the neural systems supporting declarative memory to assess the necessity of early memory to the later life development of PTSD-related symptoms. METHODS:Nineteen-day old rats were exposed to unpredictable and inescapable footshocks, and fear memory for the shock context was assessed during adulthood. Thereafter, adult animals were either exposed to single-trial fear conditioning or elevated plus maze or sacrificed for basal diurnal corticosterone and quantification of neuronal glucocorticoid and neuropeptide Y receptors. RESULTS:Early trauma exposed rats displayed stereotypic footshock reactivity, yet by adulthood, hippocampus-dependent contextual fear-related memory was absent. However, adult rats showed sensitized fear learning, aberrant basal circadian fluctuations of corticosterone, increased amygdalar glucocorticoid receptors, decreased time spent in the open arm of an elevated plus maze, and an odor aversion associated with early-life footshocks. CONCLUSIONS:These results suggest that traumatic experience during developmental periods of hippocampal immaturity can promote lifelong changes in symptoms and neuropathology associated with human PTSD, even if there is no explicit memory of the early trauma.

SUBMITTER: Poulos AM

PROVIDER: S-EPMC3984614 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats.

Poulos Andrew M AM Reger Maxine M Mehta Nehali N Zhuravka Irina I Sterlace Sarah S SS Gannam Camille C Hovda David A DA Giza Christopher C CC Fanselow Michael S MS

Biological psychiatry 20131012 4

<h4>Background</h4>Traumatic experience can result in life-long changes in the ability to cope with future stressors and emotionally salient events. These experiences, particularly during early development, are a significant risk factor for later life anxiety disorders such as posttraumatic stress disorder (PTSD). However, because traumatic experience typically results in strong episodic memories, it is not known whether such long-term memories are necessary for particular features of PTSD, such ...[more]

PMID: 24231200

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Project description:Study objectivesCharacterize associations between sleep impairments and posttraumatic stress disorder (PTSD) symptoms, including anger, in service members seeking treatment for PTSD.MethodsNinety-three US Army personnel recruited into a PTSD treatment study completed the baseline assessment. State-of-the-science sleep measurements included 1) retrospective, self-reported insomnia, 2) prospective sleep diaries assessing sleep patterns and nightmares, and 3) polysomnography measured sleep architecture and obstructive sleep apnea-hypopnea severity. Dependent variables included self-report measures of PTSD severity and anger severity. Pearson correlations and multiple linear regression analyses examined if sleep symptoms, not generally measured in PTSD populations, were associated with PTSD and anger severity.ResultsAll participants met PTSD, insomnia, and nightmare diagnostic criteria. Mean sleep efficiency = 70%, total sleep time = 5.5 hours, obstructive sleep apnea/hypopnea (obstructive sleep apnea-hypopnea index ≥ 5 events/h) = 53%, and clinically significant anger = 85%. PTSD severity was associated with insomnia severity (β = .58), nightmare severity (β = .24), nightmare frequency (β = .31), and time spent in Stage 1 sleep (β = .27, all P < .05). Anger severity was associated with insomnia severity (β = .37), nightmare severity (β = .28), and obstructive sleep apnea-hypopnea during rapid eye movement sleep (β = .31, all P < .05).ConclusionsInsomnia and nightmares were related to PTSD and anger severity, and obstructive sleep apnea-hypopnea was related to anger. Better assessment and evidence-based treatment of these comorbid sleep impairments in service members with PTSD and significant anger should result in better PTSD, anger, and quality-of-life outcomes.Clinical trials registrationRegistry: ClinicalTrials.gov; Name: Treatment of Comorbid Sleep Disorders and Post Traumatic Stress Disorder; Identifier: NCT02773693; URL: https://clinicaltrials.gov/ct2/show/NCT02773693.CitationMiles SR, Pruiksma KE, Slavis D, et al. Sleep disorder symptoms are associated with greater posttraumatic stress and anger symptoms in US Army service members seeking treatment for posttraumatic stress disorder. J Clin Sleep Med. 2022;18(6):1617-1627.

Project description:ImportancePosttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), develops only in a subset of trauma-exposed individuals. Genetic risk factors in interaction with trauma exposure have been implicated in PTSD vulnerability.ObjectiveTo examine the association of 3755 candidate gene single-nucleotide polymorphisms with PTSD development in interaction with a history of childhood trauma.Design, setting, and participantsGenetic association study in an Ohio National Guard longitudinal cohort (n = 810) of predominantly male soldiers of European ancestry, with replication in an independent Grady Trauma Project (Atlanta, Georgia) cohort (n = 2083) of predominantly female African American civilians.Main outcomes and measuresContinuous measures of PTSD severity, with a modified (interview) PTSD checklist in the discovery cohort and the PTSD Symptom Scale in the replication cohort.ResultsControlling for the level of lifetime adult trauma exposure, we identified the novel association of a single-nucleotide polymorphism within the promoter region of the ADRB2 (Online Mendelian Inheritance in Man 109690) gene with PTSD symptoms in interaction with childhood trauma (rs2400707, P = 1.02 × 10-5, significant after correction for multiple comparisons). The rs2400707 A allele was associated with relative resilience to childhood adversity. An rs2400707 × childhood trauma interaction predicting adult PTSD symptoms was replicated in the independent predominantly female African American cohort.Conclusions and relevanceAltered adrenergic and noradrenergic function has been long believed to have a key etiologic role in PTSD development; however, direct evidence of this link has been missing. The rs2400707 polymorphism has been linked to function of the adrenergic system, but, to our knowledge, this is the first study to date linking the ADRB2 gene to PTSD or any psychiatric disorders. These findings have important implications for PTSD etiology, chronic pain, and stress-related comorbidity, as well as for both primary prevention and treatment strategies.

Project description:The cancer experience may be marked by repeat stressors and/or traumas. The aim of our study was to assess traumatic events in a group of patients diagnosed with lymphoma and to determine which of these contribute to the development of Post-Traumatic Stress Disorder/PTSD. Two weeks after receiving a diagnosis of lymphoma, patients were referred for an assessment of peritraumatic distress (using the Peritraumatic Distress Inventory/PDI) and peritraumatic dissociation (using the Peritraumatic Dissociative Experiences Questionnaire/PDEQ). Three months after the diagnosis, we recorded the following parameters: the patients' worst experiences, the presence of PTSD symptoms, using the PTSD CheckList/PCL, as it related to the diagnosis, and symptoms of anxiety using the Hospital Anxiety and Depression/HAD scale and of depression using the Beck Depression Inventory/BDI-II. The study recruited 129 patients, with a mean age of 46 years (SD = 17.3); 70 (54%) men, 87 (67.5%) with Non-Hodgkin's lymphoma, and 42 with Hodgkin's lymphoma. Two weeks after the diagnosis, 49% of patients reported peritraumatic distress, and 20% peritraumatic dissociation, during or immediately after being informed of the lymphoma diagnosis. Three months after the diagnosis, the severity of PTSD symptoms was evaluated. At this stage none of the patients suffered PTSD, but 29 (23%) individuals exhibited partial PTSD: 13.4% correlated it to receiving the lymphoma diagnosis, 8% to telling family members, and 1.6% to adverse effects. Peritraumatic distress and dissociation as a result of receiving a lymphoma diagnosis, as well as anxiety and a mucositis within the first 3 months post-diagnosis, were factors that were significantly associated with PTSD symptoms, accounting for 35.8% in PTSD symptom load. Our study reveals that clinicians should assess the impact of a number of stressors, which are risk factors for PTSD symptoms, starting from the time point of the initial lymphoma diagnosis.

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Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats.

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Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats.

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