Neuroanatomical data point to functional relationships between the anterior cingulate cortex (ACC) and subcortical centers regulating fear, in particular, the amygdala. Functional brain imaging has disclosed divergent patterns of ACC activation in persons with posttraumatic stress disorder (PTSD). In addition, two preliminary structural imaging studies have found evidence of smaller ACC volume in PTSD. We explored associations between PTSD and ACC volume in a relatively large sample of adult combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed.
Subjects were US military combat veterans of the Vietnam and Gulf Wars recruited from two metropolitan areas served by allied Department of Veterans Affairs PTSD treatment/research centers. Anterior cingulate cortex volume was analyzed as a function of grouping factors with and without adjustment for body size.
Posttraumatic stress disorder was associated with smaller anterior cingulate cortex volume. This effect persisted in subjects without histories of alcoholism, did not interact with cohort effects, and was not modified by adjustment for body size.
Anterior cingulate cortex volume is substantially smaller in association with combat-related PTSD, a finding broadly consistent with cingulate hypofunctionality in that disorder.
"The ACC volume also correlated negatively to total CAPS score in the PTSD group. In a sample of 99 war veterans, the authors also reported a negative correlation between ACC volume and total Clinician-Administered PTSD Scale (CAPS) score (Woodward et al., 2006b). One study investigating a subset of PTSD (child abuse-related complex PTSD) demonstrated that patient dACC volume and the hyperarousal CAPS scores were smaller in high intensity child abuse (Thomaes et al., 2010). "
[Show abstract][Hide abstract] 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).
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).
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.
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.
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.
"Additional treatment options, particularly pharmacotherapies, are needed, as per the Institute of Medicine (2008). Literature suggests that PTSD is maintained by changes in circuits regulating memory function following traumatic stress, including connections between the amygdala and medial prefrontal cortex (mPFC); these changes comprise hyperactivity of the amygdala and hypoactivity of the mPFC [reviewed in Liberzon and Sripada (2008)], as well as decreased volume of the anterior cingulate cortex (ACC), a part of the mPFC (Woodward et al. 2006). It has been proposed that the mPFC plays a role in the " contextualization " of stimuli and that dysregulation of contextualization processes might drive PTSD symptoms. "
[Show abstract][Hide abstract] ABSTRACT: Rationale
Posttraumatic stress disorder (PTSD) and alcoholism are frequently comorbid, suggesting the possibility of overlapping neural substrates. The neurokinin 1 (NK1) receptor for substance P (SP) has been implicated in both stress- and alcohol-related behaviors. The NK1 antagonist aprepitant, clinically available as a treatment for chemotherapy-induced nausea, offers a tool to probe a potential role of the SP/NK1 system in comorbid PTSD and alcoholism.
The aim of this study is to evaluate the efficacy of aprepitant for treatment of comorbid PTSD and alcoholism.
Fifty-three patients with PTSD and alcoholism were admitted for 4 weeks to an inpatient unit at the NIH Clinical Center and randomized to double-blind aprepitant (125 mg/day; based on PET studies reporting >90 % central receptor occupancy at this dose) or placebo. After reaching steady state, subjects were assessed for PTSD symptom severity, behavioral and neuroendocrine responses to stress and alcohol cues, and functional magnetic resonance imaging (fMRI) responses to stimuli with positive or negative emotional valence.
Aprepitant treatment had no effect on PTSD symptoms or subjective or physiological responses to stress or alcohol cues. However, aprepitant robustly potentiated ventromedial prefrontal cortex (mPFC) fMRI responses to aversive visual stimuli.
Despite the lack of effect on PTSD symptoms and responses to stress/alcohol cues, NK1 antagonism activated the ventral mPFC, an area considered hypoactive in PTSD, during exposure to aversive stimuli. Because this brain area is critically important for extinction of fear memories and in alcohol craving and relapse, our finding suggests that NK1 antagonism might be a useful pharmacological treatment to enhance extinction-based cue-exposure therapies.
"As such, there are inconsistencies in reported results with both hyper- and hypoactivation observed in the aforementioned regions [25, 26]. However, anatomical studies consistently indicate reductions in amygdalar/hippocampal complex and the vmPFC/sgACC volume and represent the most replicated findings among individuals with PTSD, when compared to controls ([27–31].) Dysfunction in the vmPFC/sgACC—amygdalar/hippocampal complex pathways is suggested to be functionally associated with decreased control or regulation over fear/threat related stimuli and conditioning . "
[Show abstract][Hide abstract] ABSTRACT: A significant portion of previously deployed combat Veterans from Operation Enduring Freedom and Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) are affected by comorbid posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Despite this fact, neuroimaging studies investigating the neural correlates of cognitive dysfunction within this population are almost nonexistent, with the exception of research examining the neural correlates of diagnostic PTSD or TBI. The current study used both voxel-based and surface-based morphometry to determine whether comorbid PTSD/mTBI is characterized by altered brain structure in the same regions as observed in singular diagnostic PTSD or TBI. Furthermore, we assessed whether alterations in brain structures in these regions were associated with behavioral measures related to inhibitory control, as assessed by the Go/No-go task, self-reports of impulsivity, and/or PTSD or mTBI symptoms. Results indicate volumetric reductions in the bilateral anterior amygdala in our comorbid PTSD/mTBI sample as compared to a control sample of OEF/OIF Veterans with no history of mTBI and/or PTSD. Moreover, increased volume reduction in the amygdala predicted poorer inhibitory control as measured by performance on the Go/No-go task, increased self-reported impulsivity, and greater symptoms associated with PTSD. These findings suggest that alterations in brain anatomy in OEF/OIF/OND Veterans with comorbid PTSD/mTBI are associated with both cognitive deficits and trauma symptoms related to PTSD.
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