MRI-Based Measurement of Hippocampal Volume in Patients with Combat-Related Posttraumatic Stress Disorder

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 08/1995; 152(7):973-81. DOI: 10.1176/ajp.152.7.973
Source: PubMed


Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder.
Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse.
The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only.
These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory.

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    • "During the past decade, growing interest has been paid to the neurobiological basis of posttraumatic stress disorder (PTSD), typically indicating structural brain modifications of several grey matter formations following trauma exposure, though these results are still subject to debate. The most noticeable morphological alterations in PTSD in magnetic resonance imaging (MRI) studies were found in limbic structures, with consistent observations of hippocampal atrophy (Bremner et al., 1995, 2003; Stein et al., 1997; Gurvits et al., 1996; Lindauer et al., 2005; Kasai et al., 2008; Pavić et al., 2007; Shin et al., 2004; Pavlisa et al., 2006). Other PTSD-related volumetric reductions were noticed in the amygdala (Pavlisa et al., 2006), anterior cingulate gyrus (Rauch et al., 2003; Woodward et al., 2006a,b), corpus callosum (Villarreal et al., 2004), cerebellum (De Bellis and Kuchibhatla, 2006), and temporal and frontal grey matter (Geuze et al., 2008). "

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    • "Several other studies have reported similar negative findings [Jorge et al., 2012; Morey et al., 2012; Taber et al., 2015] although two studies using different diffusion metrics suggest white matter involvement in PTSD [Bazarian et al., 2012; Davenport et al., 2015]. Nonetheless, PTSD-related neuropathology appears to be associated primarily with changes in gray matter volume [Bremner et al., 1995; Corbo et al., 2005; Kasai et al., 2008; O'Doherty et al., 2015; Smith, 2005] and functional alterations [Bremner et al., 1999; Daniels et al., 2010; Hayes et al., 2011; Milad et al., 2009; Sadeh et al., 2015; Shin and Liberzon , 2010; Shin et al., 2004; St Jacques et al., 2013; van Wingen et al., 2012]. Further research is needed to determine if PTSD-related neuropathology independently mediates the relationship between PTSD and PCS severity. "
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    ABSTRACT: Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are non-specific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of co-morbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety OEF/OIF Veterans were assigned to one of three groups including a blast-exposed no-TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI-LOC), and a blast-related mTBI with LOC group (mTBI+LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI+LOC group had more spatially heterogeneous white matter abnormalities than those in the no-TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI+LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.
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    • "Nevertheless, neuroimaging studies have shown that the amygdala, the hippocampus, and the prefrontal cortex all play a part in stress and PTSD (McEwen, et al., 2015). For example, according to the ''glucocorticoid cascade hypothesis'' (Sapolsky, Krey & McEwen, 1986), chronic stress may cause smaller hippocampal and prefrontal cortex volume, deficits in declarative (conscious) memory and some amnesia (Baker et al., 2005; Bremner et al., 1995; Samuelson, 2011). Stress hormones triggered by way of the HPA-axis are encoded by the basolateral area of the amygdala (BLA). "
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    DESCRIPTION: Abstract Transgenerational transmission of trauma (TTT) renders some children of survivors vulnerable to stress while others become more resilient. TTT was previously assumed to be caused primarily by environmental factors, such as the parents’ child-rearing behavior. Recent research findings, reviewed in this paper, suggest that it may also be inherited through epigenetic mechanisms. New data indicate that the glucocorticoid receptor gene may cause the stress hormones of the child to become allostatic rather than resilient. Six clinical case anecdotes on suicidality, depression and PTSD, as well as on certain olfactory, cardiac and pulmonary problems, are presented to illustrate such possible epigenetic transgenerational transmission of Holocaust trauma. Further studies may justify the introduction of a new diagnostic entity -- transgenerational stress disorder -- with immediate relevance for the assessment, prevention, and treatment of the offspring of many kinds of trauma survivors.
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