Hippocampal volume in aging combat veterans with and without post-traumatic stress disorder: Relation to risk and resilience factors

The Traumatic Stress Studies Program, Psychiatry Department, Mount Sinai School of Medicine, New York, NY, United States.
Journal of Psychiatric Research (Impact Factor: 3.96). 09/2007; 41(5):435-45. DOI: 10.1016/j.jpsychires.2005.12.002
Source: PubMed


To examine whether there are post-traumatic stress disorder (PTSD) related differences in hippocampal volume in middle-aged and elderly veterans and to examine the relationship of neuroendocrine activity, memory performance, and measures of risk and resilience for PTSD to hippocampal volume in this cohort.
Seventeen veterans with chronic PTSD and 16 veterans without chronic PTSD received an MRI scan followed by neuroendocrine assessment (24-h urinary cortisol excretion and the lysozyme IC(50-DEX), a measure of glucocorticoid receptor (GR) responsiveness), and cognitive testing.
Veterans with PTSD did not differ from those without PTSD in hippocampal volume, but they did show significantly lower urinary cortisol levels, and poorer memory performance on the Wechsler Logical Memory test and Digit Span test. Smaller left hippocampal volumes were observed in veterans who developed PTSD in response to their first reported traumatic exposure, compared to veterans who had first experienced a traumatic event to which they did not develop PTSD, prior to experiencing a subsequent event that led to PTSD. In contrast, the two neuroendocrine measures were associated with risk factors related to early trauma exposure.
Although hippocampal volume was not found to differ between subjects with and without PTSD, smaller hippocampal volumes in PTSD may be associated with specific risk and resilience factors. These may be distinct from vulnerability markers associated with increased responsiveness to glucocorticoids and/or other neuroendocrine measures that have been observed in combat-related PTSD.

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    • "Moreover, the fact that the hippocampus and amygdala were differentially affected by early-and late-life stress suggests that the hippocampus is more vulnerable to early detrimental effects, whereas the amygdala is more reactive to stressful events occurring during later stages of life. Even though the current findings fit well with past research (McEwen, 2001; Bremner, 2006; Yehuda et al. 2007; Tottenham et al. 2010), the possibility of reversed causality cannot be excluded. For instance, individuals with smaller hippocampal volume and larger amygdala volume might report more negative life events as a result of impaired emotion regulation (Gerritsen et al. 2012). "
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    ABSTRACT: Background: Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults. Method: In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning. Results: Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women. Conclusions: These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.
    Psychological Medicine 10/2014; 45(06):1-10. DOI:10.1017/S0033291714002293 · 5.94 Impact Factor
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    • "The clinical picture presented by patients who develop PTSD is thought to reflect on structural and functional changes in specific areas of the brain (Bremner, 2007). Neuroimaging studies have consistently shown altered limbic and paralimbic structures, mainly in the hippocampus, (Golub et al., 2011; Schmahl et al., 2009; Woon and Hedges, 2008; Hara et al., 2008; Bossini et al., 2008; Yehuda et al., 2007; Pavic et al., 2007) amygdala, (Woodward et al., 2006b; Woon and Hedges, 2008; Hara et al., 2008; Rogers et al., 2009a) insula, (Chen et al., 2006) and anterior cingulate cortex (ACC) (Thomaes et al., 2010; Woodward et al., 2006b; Rogers et al., 2009a; Kitayama et al., 2006a). These areas play an important role in the anxiety response and, most likely, in PTSD pathophysiology. "
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    • "Notably, reduced gray matter volume within these regions was not found in monozygotic twins discordant for the development of PTSD, suggesting that it reflects a consequence rather than a predisposing risk factor for the disorder (Kasai et al., 2008). Hippocampal gray matter reduction in PTSD vs. Non-PTSD subjects is among the most replicated finding in this literature (Bonne et al., 2008; Bremner et al., 1997; Chen et al., 2006; Emdad et al., 2006; Felmingham et al., 2009; Gurvits et al., 1996; Lindauer et al., 2004; Thomaes et al., 2010; Villarreal et al., 2002; Vythilingam et al., 2005; Wang et al., 2010; Winter & Irle, 2004; Yehuda et al., 2007), although some have failed to find such differences (Bonne et al., 2001; Fennema-Notestine, Stein, Kennedy, Archibald, & Jernigan, 2002; Golier et al., 2005; Pederson et al., 2004). Some evidence suggests that small hippocampal volume may confer a biological vulnerability to developing PTSD if exposed to a traumatic event (Gilbertson et al., 2002). "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is associated with functional abnormalities within a neurocircuitry that includes the hippocampus, amygdala, and medial prefrontal cortex. Evidence of structural abnormalities within these regions, and their association with PTSD severity and symptom burden is, however, sparse. The present study evaluated the relation between indices of gray matter volume and PTSD symptom severity using voxel-based morphometry. Fifteen individuals meeting DSM-IV criteria for PTSD completed the Clinician Administered PTSD Scale and underwent structural magnetic resonance imaging. Greater PTSD severity and avoidance/numbing were correlated with increased gray matter volume of the right amygdala-hippocampal complex. Greater hyper-arousal was associated with reduced gray matter volume in the left superior medial frontal gyrus. Findings are consistent with current neurocircuitry models of PTSD, which posit that the disorder is associated with structural and functional variance within this distributed network.
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