Clarifying the Origin of Biological Abnormalities in PTSD Through the Study of Identical Twins Discordant for Combat Exposure

Article (PDF Available)inAnnals of the New York Academy of Sciences 1071(1):242-54 · August 2006with26 Reads
DOI: 10.1196/annals.1364.019 · Source: PubMed
Abstract
A biological abnormality found to be associated with posttraumatic stress disorder (PTSD) may be, among other things, a pretrauma vulnerability factor, that is, it may have been present prior to the event's occurrence and increased the individual's likelihood of developing PTSD upon traumatic exposure. Alternately, it may be an acquired PTSD sign, that is, it may have developed after the traumatic exposure, along with the PTSD. We have studied pairs of Vietnam combat veterans and their noncombat-exposed, identical twins in an effort to resolve these competing origins. Combat veterans were diagnosed as current PTSD or non-PTSD (i.e., never had). Average heart rate responses (HRRs) to a series of sudden, loud-tone presentations were larger in Vietnam combat veteran twins with PTSD, but these larger responses were not shared by their noncombat-exposed cotwins, whose responses were similar to those of the non-PTSD combat veterans and their noncombat-exposed cotwins. These results suggest that larger HRRs to sudden, loud tones represent an acquired sign of PTSD. In contrast, increased neurological soft signs (NSSs), diminished hippocampal volume, and presence of abnormal cavum septum pellucidum (CSP) were found in Vietnam combat veteran twins with PTSD and their "high-risk," unexposed cotwins compared to Vietnam combat veteran twins without PTSD and their "low-risk," unexposed cotwins. These results support the conclusion that the latter abnormalities represent antecedent, familial vulnerability factors for developing chronic PTSD upon exposure to a traumatic event.
    • "Yehuda et al. (2005) documented in utero transmission of hypocortisolism in children whose mother was traumatically impacted by the events of September 11th, particularly during the third trimester of pregnancy. These effects are also potentially explained through genetic and epigenetic programming (Pitman et al., 2006; Pratchett and Yehuda, 2014). Animal models also highlight the importance of intergenerational transmission of differences in the expression of glucocorticoid receptor genes (Francis et al., 1999). "
    [Show abstract] [Hide abstract] ABSTRACT: Parental Posttraumatic Stress Disorder (PTSD), particularly maternal PTSD, confers risk for stress-related psychopathology among offspring. Altered hypothalamic-pituitary-adrenal (HPA) axis functioning is one mechanism proposed to explain transmission of this intergenerational risk. Investigation of this mechanism has been largely limited to general stress response (e.g., diurnal cortisol), rather than reactivity in response to an acute stressor. We examined cortisol reactivity in response to a laboratory stressor among offspring of mothers with a lifetime diagnosis of PTSD (n=36) and age- and gender- matched control offspring of mothers without PTSD (n=36). Youth (67% girls; mean age=11.4, SD=2.6) participated in a developmentally sensitive laboratory stressor and had salivary cortisol assessed five times (one pre-stress, one immediate post-stress, and three recovery measures, spaced 15min apart). Results were consistent with the hypothesis that offspring of mothers with PTSD would exhibit a dysregulated, blunted cortisol reactivity profile, and control offspring would display the expected adaptive peak in cortisol response to challenge profile. Findings were maintained after controlling for youth traumatic event history, physical anxiety symptoms, and depression, as well as maternal depression. This finding contributes to the existing literature indicating that attenuated HPA axis functioning, inclusive of hyposecretion of cortisol in response to acute stress, is robust among youth of mothers with PTSD. Future research is warranted in elucidating cortisol reactivity as a link between maternal PTSD and stress-related psychopathology vulnerability among offspring. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jan 2015
    • "Several potential PTSD biomarkers including disturbances in hormones or neurotransmitter systems, impaired physiological responses to stimuli, and structural or functional brain abnormalities have been investigated (Lanius et al., 2002; Yehuda et al., 2002; Karl et al., 2006; Pitman et al., 2006; Geuze et al., 2008; Kovacic et al., 2008; Eckart et al., 2011; Zolad and Diamond, 2013); yet, none have previously emerged as definitive PTSD biomarkers. Indeed, to be useful, a PTSD biomarker must first be both reproducible and highly accurate; many previously proposed biomarkers meet one but not both of these criteria. "
    [Show abstract] [Hide abstract] ABSTRACT: Intact cognitive functions rely on synchronous neural activity; conversely, alterations in synchrony are thought to underlie psychopathology. We recently demonstrated that anomalies in synchronous neural interactions (SNI) determined by magnetoencephalography represent a putative PTSD biomarker. Here we develop and apply a regression-based diagnostic algorithm to further validate SNI as a PTSD biomarker in 432 veterans (235 controls; 138 pure PTSD; 59 PTSD plus comorbid disorders). Correlation coefficients served as proximities in multidimensional scaling (MDS) to obtain a two-dimensional representation of the data. In addition, least absolute shrinkage and selection operator (LASSO) regression was used to derive a diagnostic algorithm for PTSD. Performance of this algorithm was assessed by the area under the receiver operating characteristic (ROC) curves, sensitivity, and specificity in 1000 randomly divided testing and validation datasets and in independent samples. MDS revealed that individuals with PTSD, regardless of comorbid psychiatric conditions, are highly distinct from controls. Similarly, application of the LASSO regression-derived prediction model demonstrated remarkable classification accuracy (AUCs≥0.93 for men, AUC=0.82 for women). Neural functioning in individuals with PTSD, regardless of comorbid psychiatric diagnoses, can be used as a diagnostic test to determine patient disease status, further validating SNI as a PTSD biomarker.
    Full-text · Article · Nov 2014
    • "Early animal models have shown alterations in the hippocampus, amygdala , and medial prefrontal cortex as a result of exposure to excessive stress [8] . Human studies have indicated that there are also functional changes in these and other brain regions after exposure to a traumatic event [7, 9] ; however , the exact mechanism of these changes remains unknown [8]. This section will describe the observed changes in the key regions associated with PTSD: the prefrontal cortex, amygdala, and hippocampus. "
    [Show abstract] [Hide abstract] ABSTRACT: While there has been an abundance of research on Post-Traumatic Stress Disorder (PTSD) in the past several decades, clinical studies on the neurobiological mechanisms involved in the disorder are only recently receiving attention. This paper will collate available information on the neurobiology of PTSD for clinical and lay audiences. This paper reviews the literature surrounding typical symptoms of PTSD, with a specific focus on the neurobiological evidence suggesting altered brain functioning among those with the condition. It will also present literature reviewing common treatment methods of PTSD and their potential effects on brain functioning, including attention, working memory, and emotional regulation. The concept of post-traumatic growth will also be introduced, indicating an alternate trajectory of PTSD.
    Article · Sep 2014
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