Neural circuitry of PTSD with or without mild traumatic brain injury: A meta-analysis

Veteran Affairs, San Diego, CA 92161, USA.
Neuropharmacology (Impact Factor: 5.11). 03/2011; 62(2):598-606. DOI: 10.1016/j.neuropharm.2011.03.016
Source: PubMed


Posttraumatic Stress Disorder (PTSD) and mild traumatic brain injury (mTBI) often occur together. Parsing out the unique and overlapping effects of these conditions on the brain, can inform the selection of appropriate treatments. Although recent studies indicate that warfighters in Operations Enduring and Iraqi Freedom are at a high risk for PTSD and mTBI, there is a dearth of research directly comparing their neural correlates. In this paper, we briefly discuss these conditions and supply two meta-analyses of the relevant functional magnetic resonance imaging studies conducted to date. By looking at the overlap in these analyses, we suggest that the middle frontal gyrus may be an appropriate area for future investigations aimed at disentangling PTSD and mTBI. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

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    • "In the present study, probable PTSD showed the strongest association with psychomotor speed (d=0.29) which is congruent with Scott et al. (2015); albeit our effect size was much smaller and T-scores were in the normal range, thus these associations may be statistically rather than clinically significant. In HIV− individuals with PTSD, functional abnormalities in the prefrontal cortex (Sartory et al. 2013; Simmons and Matthews 2012) are linked to processing speed impairments (Aupperle et al. 2012). Specifically, in a sample of women with PTSD related to intimate partner violence, hypoactivation in the dorsal lateral prefrontal cortex (DLPFC) was associated with impairments in a standardized measure of processing speed (Aupperle et al. 2012). "
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    ABSTRACT: The prevalence of post-traumatic stress disorder (PTSD) is higher among HIV-infected (HIV+) women compared with HIV-uninfected (HIV-) women, and deficits in episodic memory are a common feature of both PTSD and HIV infection. We investigated the association between a probable PTSD diagnosis using the PTSD Checklist-Civilian (PCL-C) version and verbal learning and memory using the Hopkins Verbal Learning Test in 1004 HIV+ and 496 at-risk HIV- women. HIV infection was not associated with a probable PTSD diagnosis (17 % HIV+, 16 % HIV-; p = 0.49) but was associated with lower verbal learning (p < 0.01) and memory scores (p < 0.01). Irrespective of HIV status, a probable PTSD diagnosis was associated with poorer performance in verbal learning (p < 0.01) and memory (p < 0.01) and psychomotor speed (p < 0.001). The particular pattern of cognitive correlates of probable PTSD varied depending on exposure to sexual abuse and/or violence, with exposure to either being associated with a greater number of cognitive domains and a worse cognitive profile. A statistical interaction between HIV serostatus and PTSD was observed on the fine motor skills domain (p = 0.03). Among women with probable PTSD, HIV- women performed worse than HIV+ women on fine motor skills (p = 0.01), but among women without probable PTSD, there was no significant difference in performance between the groups (p = 0.59). These findings underscore the importance of considering mental health factors as correlates to cognitive deficits in women with HIV.
    Journal of NeuroVirology 09/2015; DOI:10.1007/s13365-015-0380-9 · 2.60 Impact Factor
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    • "In turn, abnormal function of the medial prefrontal cortex impairs the inhibition of fear circuitry in PTSD (abnormal topdown regulation) (Rauch et al., 2006; Liberzon and Sripada, 2008). The insula is also affected, thus reflecting an abnormal integration between bodily function and emotions (Simmons and Matthews, 2012). The hippocampus may also be affected, which reflects declarative memory impairment and impaired regulation of the HPA axis (Rauch et al., 2006). "
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    ABSTRACT: Background To evaluate differences in limbic structure volume of subjects exposed to urban violence during adulthood, between those who developed posttraumatic stress disorder (with PTSD) and resilient matched controls (without PTSD). Methods Limbic volumetric measures of 32 subjects with PTSD and 32 subjects without PTSD who underwent brain MRI were analyzed in an epidemiological study in the city of Sao Paulo. The hippocampus, amygdala, cingulate, and parahipocampal gyri volumes were estimated using FreeSurfer software. We also investigated the association between limbic volumetric measurements, symptom´s severity, and early life stress history (measure by Early Trauma Inventory – ETI). Results Subjects with PTSD presented reduced volume of the right rostral part of the anterior cingulate, compared to subjects without PTSD, after controlling for intracranial volume, ETI, and depressive symptoms. Subjects with PTSD presented larger bilateral hippocampus and right amygdala, but secondary to the higher ETI. In PTSD group there was a positive correlation between ETI with bilateral hippocampus, bilateral amygdala, and left parahippocampus. Limitations First, the cross-sectional study design precludes causal interpretation of limbic structure reduction in PTSD, consequence of PTSD, or other life events. Finally, since the sample size was not sufficiently large, we could not observe whether or not limbic structure volume could be related to the type of trauma. Conclusions The present study provides evidence of a reduced anterior cingulate volume in subjects with PTSD than in resilient subjects exposed to urban violence. Enlargement of hippocampus and amygdala volume was observed in subjects with PTSD, however secondary to early trauma experience.
    Journal of Affective Disorders 10/2014; 168:13–20. DOI:10.1016/j.jad.2014.06.036 · 3.38 Impact Factor
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    • "Etkin and Wager [16] compared PTSD with other anxiety disorders and found amygdalar hyperactivation in all disorders but dorsal and rostral cingulate hypoactivation only in PTSD. Assuming that PTSD results in fundamental alteration of brain function, Patel et al. [34] and Simmons and Matthews [35] carried out meta-analyses across a variety of conditions and cognitive tasks. Patel et al. [34] confirmed the activation pattern reported by Etkin and Wager [16] and found additional hyperactivation in the hippocampus. "
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    ABSTRACT: Notwithstanding some discrepancy between results from neuroimaging studies of symptom provocation in posttraumatic stress disorder (PTSD), there is broad agreement as to the neural circuit underlying this disorder. It is thought to be characterized by an exaggerated amygdalar and decreased medial prefrontal activation to which the elevated anxiety state and concomitant inadequate emotional regulation are attributed. However, the proposed circuit falls short of accounting for the main symptom, unique among anxiety disorders to PTSD, namely, reexperiencing the precipitating event in the form of recurrent, distressing images and recollections. Owing to the technical demands, neuroimaging studies are usually carried out with small sample sizes. A meta-analysis of their findings is more likely to cast light on the involved cortical areas. Coordinate-based meta-analyses employing ES-SDM (Effect Size Signed Differential Mapping) were carried out on 19 studies with 274 PTSD patients. Thirteen of the studies included 145 trauma-exposed control participants. Comparisons between reactions to trauma-related stimuli and a control condition and group comparison of reactions to the trauma-related stimuli were submitted to meta-analysis. Compared to controls and the neutral condition, PTSD patients showed significant activation of the mid-line retrosplenial cortex and precuneus in response to trauma-related stimuli. These midline areas have been implicated in self-referential processing and salient autobiographical memory. PTSD patients also evidenced hyperactivation of the pregenual/anterior cingulate gyrus and bilateral amygdala to trauma-relevant, compared to neutral, stimuli. Patients showed significantly less activation than controls in sensory association areas such as the bilateral temporal gyri and extrastriate area which may indicate that the patients' attention was diverted from the presented stimuli by being focused on the elicited trauma memory. Being involved in associative learning and priming, the retrosplenial cortex may have an important function in relation to trauma memory, in particular, the intrusive reexperiencing of the traumatic event.
    PLoS ONE 03/2013; 8(3):e58150. DOI:10.1371/journal.pone.0058150 · 3.23 Impact Factor
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