Schuff N, Neylan TC, Fox-Bosetti S, Lenoci M, Samuelson KW, Studholme C et al. Abnormal N-acetylaspartate in hippocampus and anterior cingulate in posttraumatic stress disorder. Psychiatry Res 162: 147-157

Center for Imaging of Neurodegenerative Diseases, DVA Medical Center, San Francisco, CA 94121, USA.
Psychiatry Research (Impact Factor: 2.47). 03/2008; 162(2):147-57. DOI: 10.1016/j.pscychresns.2007.04.011
Source: PubMed


Magnetic resonance spectroscopic imaging (MRSI) studies suggest hippocampal abnormalities in posttraumatic stress disorder (PTSD), whereas findings of volume deficits in the hippocampus, as revealed with magnetic resonance imaging (MRI), have been inconsistent. Co-morbidities of PTSD, notably alcohol abuse, may have contributed to the inconsistency. The objective was to determine whether volumetric and metabolic abnormalities in the hippocampus and other brain regions are present in PTSD, independent of alcohol abuse. Four groups of subjects, PTSD patients with (n=28) and without (n=27) alcohol abuse and subjects negative for PTSD with (n=23) and without (n=26) alcohol abuse, were enrolled in this observational MRI and MRSI study of structural and metabolic brain abnormalities in PTSD. PTSD was associated with reduced N-acetylaspartate (NAA) in both the left and right hippocampus, though only when normalized to creatine levels in the absence of significant hippocampal volume reduction. Furthermore, PTSD was associated with reduced NAA in the right anterior cingulate cortex regardless of creatine. NAA appears to be a more sensitive marker for neuronal abnormality in PTSD than brain volume. The alteration in the anterior cingulate cortex in PTSD has implications for fear conditioning and extinction.

18 Reads
  • Source
    • "Using 1 H MRS methods identical to those employed in this study, we showed (Mon et al., 2012) lower concentrations of Glu, NAA, and Cr in the ACC of recently detoxified alcohol-dependent individuals compared with nondrinking or light-drinking controls, and normal ACC GABA and mI concentrations; however, metabolite levels in the dorsolateral prefrontal cortex and POC were not abnormal in these alcoholdependent individuals (Mon et al., 2012). One 1 H MRS study of PTSD investigated the effects of alcohol consumption on brain metabolite concentrations (Schuff et al., 2008). Both PTSD patients with little or no alcohol consumption and PTSD patients with a history of alcohol abuse within the 5 preceding years had low NAA/Cr in the ACC and mesial temporal lobe including the hippocampus. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Posttraumatic stress disorder (PTSD) patients have low cortical concentrations of γ-aminobutyric acid (GABA) and elevated glutamate (Glu) as measured by proton magnetic resonance spectroscopy (1H MRS). Alcohol use disorder (AUD) is highly comorbid with PTSD, but the neurobiological underpinnings are largely unknown. We wanted to determine if PTSD patients with AUD have normalized cortical GABA and Glu levels in addition to metabolite alterations common to AUD. We compared brain metabolite concentrations in 10 PTSD patients with comorbid AUD (PAUD) with concentrtations in 28 PTSD patients without AUD and in 20 trauma-exposed controls (CON) without PTSD symptoms. We measured concentrations of GABA, Glu, N-acetylaspartate (NAA), creatine- (Cr) and choline-containing metabolites (Cho), and myo-Inositol (mI) in three cortical brain regions using 1H MRS and correlated them with measures of neurocognition, insomnia, PTSD symptoms, and drinking severity. In contrast to PTSD, PAUD exhibited normal GABA and Glu concentrations in the parieto-occipital and temporal cortices, respectively, but lower Glu and trends toward higher GABA levels in the anterior cingulate cortex (ACC). Temporal NAA and Cho as well as mI in the ACC were lower in PAUD than in both PTSD and CON. Within PAUD, more cortical GABA and Glu correlated with better neurocognition. Heavy drinking in PTSD is associated with partially neutralized neurotransmitter imbalance, but also with neuronal injury commonly observed in AUD.
    Psychiatry Research: Neuroimaging 12/2014; 224(3). DOI:10.1016/j.pscychresns.2014.09.004 · 2.42 Impact Factor
  • Source
    • "Other major hypotheses are (1) that TBI and/or PTSD reduce cognitive reserve, causing greater cognitive impairment after accounting for age, educational status, prewar cognitive function, brain amyloid load, or hippocampal volume; and (2) that there are significant correlations between severity of TBI and/or the severity of PTSD, and greater cognitive impairment. We are also seeking to replicate reports that TBI is associated with reduced microstructural integrity in brain white matter in specific brain regions [79] [80] [81] and that PTSD is associated with reduced hippocampal volume compared with control subjects [50] [51] [52] [53] [54]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans.
    Alzheimer's and Dementia 06/2014; 10(3):S226–S235. DOI:10.1016/j.jalz.2014.04.005 · 12.41 Impact Factor
  • Source
    • "Multiple studies have identified smaller hippocampal volumes in subjects with posttraumatic stress disorder (PTSD) [2] [3] [4] [5] [6] [7]. Not all studies have found smaller hippocampal volumes [8] [9] [10] [11], and various groups have suggested that hippocampal volume differences in PTSD are attributable to comorbid conditions such as alcoholism [12] or depression [13]. Still, in most studies of hippocampal volume in PTSD investigators have controlled for major psychiatric comorbidities , including substance abuse, and meta-analyses reveal that the correlation between PTSD and smaller hippocampal volume is widely replicated [6,14–16]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.
    Alzheimer's and Dementia 06/2014; 10(3):S146–S154. DOI:10.1016/j.jalz.2014.04.016 · 12.41 Impact Factor
Show more