MRI-based measurement of hippocampal volume in patients with combat- related posttraumatic stress disorder

Bremner, J. Douglas; Randall, Penny K.; Scott, Tammy; Bronen, Richard A.; Seibyl, John; Southwick, Steven M.; Delaney, Richard; McCarthy, Gregory; Charney, Dennis S.; Innis, Robert B.

doi:10.1176/ajp.152.7.973

Cited by 1,299 publications

(186 citation statements)

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“…Reduced hippocampal volumes, as well as altered hippocampal function, have also been reported in other mood disorders, including post-traumatic stress disorder (Bremner et al, 1995) and obsessive-compulsive disorder (Atmaca et al, 2008). In addition, altered hippocampal connectivity has been reported in depressive (Sheline et al, 2010) and anxiety disorders (Etkin et al, 2009).…”

Section: Discussionmentioning

confidence: 94%

A multimodal MRI study of the hippocampus in medication-naive children with ADHD: What connects ADHD and depression?

Posner

Siciliano

Wang

et al. 2014

Psychiatry Research: Neuroimaging

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Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing depression. The neurobiological substrates that convey this risk remain poorly understood. On the basis of considerable data implicating hippocampal abnormalities in depressive disorders, we aimed to explore the relationship between the hippocampus and levels of depressive symptomatology in ADHD. We used structural magnetic resonance imaging (MRI) to examine the functional magnetic resonance imaging (fMRI) to assess the resting state functional connectivity (rs-fcMRI) of the hippocampus in a sample of 32 medication-naive children with ADHD (ages 6–13) and 33 age- and sex-matched healthy control (HC) participants. Compared with the HC participants, the participants with ADHD had (i) reduced volumes of the left hippocampus and (ii) reduced functional connectivity (rs-fcMRI) between the left hippocampus and the left orbitofrontal cortex (OFC); these hippocampal effects were associated with more severe depressive symptoms, even after controlling for the severity of inattentive and hyperactive/impulsive symptoms. Altered hippocampal structure and connectivity were not associated with anxiety or more general internalizing symptoms. Though preliminary, these findings suggest that the relationship between hippocampal anomalies and ADHD youth's susceptibility to developing depression and other mood disorders may merit further investigation with follow-up longitudinal research.

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Section: Discussionmentioning

confidence: 94%

A multimodal MRI study of the hippocampus in medication-naive children with ADHD: What connects ADHD and depression?

Posner

Siciliano

Wang

et al. 2014

Psychiatry Research: Neuroimaging

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“…Both structures have ample a priori evidence implicating their role in PTSD starting with the report of reduced hippocampal volume in PTSD by Bremner et al in 1995 (64). Our study confirms this finding across a large number of demographically and clinically heterogeneous cohorts analyzed with standardized segmentation technique, and running a harmonized analysis protocol across all sites.…”

Section: Discussionmentioning

confidence: 99%

Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia

Logue

Rooij

Dennis

et al. 2018

Biological Psychiatry

380

247

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BACKGROUND Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma.

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“…23 Hippocampal neuronal atrophy may be explained in part by higher levels of glucocorticoids, as increased levels of glucocorticoids significantly inhibit glucose uptake by neurons not only in hippocampal cells 24 but also in most cell types. This inhibition renders the neurons and other cells susceptible to damage by free radicals and other mechanisms.…”

Section: Connecting the Dots: The Influence Of Adrenergic Agents Andmentioning

confidence: 99%

Post‐traumatic stress disorder: revisiting adrenergics, glucocorticoids, immune system effects and homeostasis.

2014

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This review focuses on post-traumatic stress disorder (PTSD). Several sequelae of PTSD are partially attributed to glucocorticoid-induced neuronal loss in the hippocampus and amygdala. Glucocorticoids and adrenergic agents cause both immediate and late sequelae and are considered from the perspective of their actions on the expression of cytokines as well as some of their physiological and psychological effects. A shift in immune system balance from Th1 to Th2 dominance is thought to result from the actions of both molecular groups. The secretion of glucocorticoids and adrenergic agents is commonly induced by trauma or stress, and synergy between these two parallel but separate pathways can produce long- and short-term sequelae in individuals with PTSD. Potential therapies are suggested, and older therapies that involve the early effects of adrenergics or glucocorticoids are reviewed for their control of acute symptoms. These therapies may also be useful for acute flashback therapy. Timely and more precise glucocorticoid and adrenergic control is recommended for maintaining these molecular groups within acceptable homeostatic limits and thus managing immune and brain sequelae. Psychotherapy should supplement the above therapeutic measures; however, psychotherapy is not the focus of this paper. Instead, this review focuses on the probable molecular basis of PTSD. Integrating historical findings regarding glucocorticoids and adrenergic agents into current research and clinical applications returns the focus to potentially life-changing treatments. Autologous adoptive immune therapy may also offer utility. This paper reports clinical and translational research that connects and challenges separate fields of study, current and classical, in an attempt to better understand and ameliorate the effects of PTSD.

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MRI-based measurement of hippocampal volume in patients with combat- related posttraumatic stress disorder

Abstract: These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory.

Cited by 1,299 publications

References 50 publications

A multimodal MRI study of the hippocampus in medication-naive children with ADHD: What connects ADHD and depression?

A multimodal MRI study of the hippocampus in medication-naive children with ADHD: What connects ADHD and depression?

Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia

Post‐traumatic stress disorder: revisiting adrenergics, glucocorticoids, immune system effects and homeostasis.

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