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ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

ABSTRACT: Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.

SUBMITTER: Johnson LA

PROVIDER: S-EPMC4538360 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

Johnson Lance A LA Zuloaga Damian G DG Bidiman Erin E Marzulla Tessa T Weber Sydney S Wahbeh Helane H Raber Jacob J

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150510 10

Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). Howev ...[more]

PMID: 25857685

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Project description:Posttraumatic stress disorder (PTSD) is a prevalent condition associated with intimate relationship problems, and intimate relationship factors have been shown to affect individual PTSD treatment outcomes.To compare cognitive-behavioral conjoint therapy for PTSD (a manualized couple therapy delivered to patients with PTSD and their significant others to simultaneously treat PTSD symptoms and enhance relationship satisfaction) with a wait-list condition.Randomized controlled trial of heterosexual and same-sex couples (n = 40 couples; n = 80 individuals) in which one partner met criteria for PTSD according to the Clinician-Administered PTSD Scale, conducted from 2008 to 2012 in a Department of Veterans Affairs outpatient hospital setting in Boston, Massachusetts, and a university-based research center in Toronto, Ontario, Canada. Symptoms of PTSD, comorbid conditions, and relationship satisfaction were collected by blinded assessors at baseline, at mid treatment (median, 8.00 weeks [range, 1.71-20.43 weeks] after baseline), and at posttreatment (median, 15.86 weeks [range, 7.14-38.57 weeks] after baseline). An uncontrolled 3-month follow-up (median, 38.21 weeks [range, 28.43-50.57 weeks] after baseline) was also completed.Couples were randomly assigned to take part in the 15-session cognitive-behavioral conjoint therapy for PTSD protocol immediately (n = 20) or were placed on a wait list for the therapy (n = 20).Clinician-rated PTSD symptom severity was the primary outcome and was assessed with the Clinician-Administered PTSD Scale. Intimate relationship satisfaction, assessed with the Dyadic Adjustment Scale, patient- and partner-rated PTSD symptoms, and comorbid symptoms were secondary outcomes.PTSD symptom severity (score range, 0-136) was significantly more improved in the couple therapy condition than in the wait-list condition (mean change difference, -23.21; 95% CI, -37.87 to -8.55). Similarly, patients' intimate relationship satisfaction (score range, 0-151) was significantly more improved in couple therapy than in the wait-list condition (mean change difference, 9.43; 95% CI, 0.04-18.83). The time × condition interaction effect in the multilevel model predicting PTSD symptoms (t37.5 = -3.09; P = .004) and patient-reported relationship satisfaction (t68.5 = 2.00; P = .049) revealed superiority of the couple therapy compared with the wait list. Treatment effects were maintained at 3-month follow-up.Among couples in which one partner was diagnosed as having PTSD, a disorder-specific couple therapy, compared with a wait list for the therapy, resulted in decreased PTSD symptom severity and patient comorbid symptom severity and increased patient relationship satisfaction.clinicaltrials.gov Identifier: NCT00669981.

Dataset Information

ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

Publications

ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

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