Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: A meta-analysis of structural MRI studies

Abstract

Over the last decade a significant number of studies have reported smaller hippocampal volume in individuals with symptoms of post-traumatic stress disorder (PTSD) relative to control groups, and in some cases hemispheric asymmetries in this effect have been noted. However these reported asymmetries have not been in a consistent direction, and other well-controlled studies have failed to observe any hippocampal volume difference. This paper reports a systematic review and meta-analysis of studies in which hippocampal volume was estimated from magnetic resonance images in adult patients with PTSD. After applying a variety of selection criteria intended to minimize potential confounds in pooled effect-size estimates, the meta-analysis included 13 studies of adult patients with PTSD that compared the patients to well-matched control groups, for a total of 215 patients and 325 control subjects. The studies varied with respect to participant age, gender distribution, source of trauma, severity of symptoms, duration of disorder, the nature of the control groups, and the methods employed for volumetric quantification. Despite these differences, pooled effect size calculations across the studies indicated significant volume differences in both hemispheres. On average PTSD patients had a 6.9% smaller left hippocampal volume and a 6.6% smaller right hippocampal volume compared with control subjects. These volume differences were smaller when comparing PTSD patients with control subjects exposed to similar levels of trauma, and larger when comparing PTSD patients to control subjects without significant trauma exposure. Such differences are consistent with the notion that exposure to stressful experiences can lead to hippocampal atrophy, although prospective studies would be necessary to unambiguously establish such a relationship.

Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus

“…This main finding agrees with those from prior animal studies (Fuchs and Flugge, 1998;Kim and Diamond, 2002;McEwen, 1999;Miller and O'Callaghan, 2005) and human clinical MRI studies Geuze et al, 2005;Kitayama et al, 2005;Smith, 2005) indicating that chronic stress is associated with a decreased volume of the hippocampus. To our knowledge, this is the first report of a relationship between a prospectively measured indicator of chronic life stress and hippocampal grey matter volume among otherwise healthy individuals.…”

“…Right-lateralized decreases in hippocampal volume are observed in major depressive disorder (O'Brien et al, 2004) and in post-traumatic stress disorder (Bremner et al, 1995), although the mechanisms explaining these unilateral findings are unknown Kitayama et al, 2005;Smith, 2005;Van Petten, 2004). One speculation (Bremner et al, 1995), with some support from the animal literature (Sullivan and Gratton, 2002), is that an asymmetric concentration of stressrelated neurotransmitters, such as serotonin, may partly mediate right-lateralized chronic-stress related changes in the structure and function of the hippocampus and related circuitry.…”

“…With noted exceptions, chronic stressful experiences are also associated with a decreased volume of the hippocampus and with impaired hippocampal-dependent functions in humans with stress-related psychiatric syndromes, including major depressive disorder and posttraumatic stress disorder (Campbell et al, 2004a;Geuze et al, 2005;Kitayama et al, 2005;Smith, 2005). Specific findings from clinical MRI studies agree with animal models of chronic stress and hippocampal atrophy.…”

Biomarkers for the Diagnosis, Prognosis, and Evaluation of Treatment Efficacy for Traumatic Brain Injury

“…A few MRI studies have reported that patients with PTSD have smaller hippocampal volumes, which could be used for the diagnosis of PTSD. 106,107 However, it has been argued that smaller hippocampal volume may reflect a pre-existing vulnerability rather than resulting from the traumatic event. 108 It is believed that PTSD symptoms result from a hypoactive medial prefrontal cortex and a hyperactive amygdala, which is supported by experimental findings in animals and humans.…”

Stressor-Specific Regulation of Distinct Brain-Derived Neurotrophic Factor Transcripts and Cyclic AMP Response Element-Binding Protein Expression in the Postnatal and Adult Rat Hippocampus

“…Patients suffering from major depression or post-traumatic stress disorder have been reported to exhibit hippocampal volumetric loss (Bremner et al, 2000;Smith, 2005). In animal models, sustained exposure to stress is known to induce dendritic atrophy within the hippocampal CA subfields (Magarinos et al, 1996;Vyas et al, 2002) and to decrease neurogenesis in the dentate gyrus (DG) (Mirescu and Gould, 2006;Pham et al, 2003).…”