Admon R, Milad MR, Hendle T (2013). A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities

Center for Depression, Anxiety and Stress Research, McLean Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: .
Trends in Cognitive Sciences (Impact Factor: 21.97). 06/2013; 17(7). DOI: 10.1016/j.tics.2013.05.005
Source: PubMed


Discriminating neural abnormalities into the causes versus consequences of psychopathology would enhance the translation of neuroimaging findings into clinical practice. By regarding the traumatic encounter as a reference point for disease onset, neuroimaging studies of post-traumatic stress disorder (PTSD) can potentially allocate PTSD neural abnormalities to either predisposing (pre-exposure) or acquired (post-exposure) factors. Based on novel research strategies in PTSD neuroimaging, including genetic, environmental, twin, and prospective studies, we provide a causal model that accounts for neural abnormalities in PTSD, and outline its clinical implications. Current data suggest that abnormalities within the amygdala and dorsal anterior cingulate cortex represent predisposing risk factors for developing PTSD, whereas dysfunctional hippocampal-ventromedial prefrontal cortex (vmPFC) interactions may become evident only after having developed the disorder.

Download full-text


Available from: Roee Admon,
  • Source
    • "We hypothesized that soldiers with danger-based traumas would manifest greater resting neuronal activity in brain regions involved in heightened fear or hyperarousal (amygdalae), possibly indicating nascent defensive states, whereas non-danger-based traumas would be associated with brain regions involved in emotion regulation (rostral or dorsal anterior cingulate cortex— dACC; cf. Admon et al., 2013). We tested our hypotheses using a priori region of interest (ROI) analyses of brain regions most commonly active under fear-based conditions or uniquely implicated in PTSD during trauma script imagery. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiol-ogy of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with 18 fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger-(n ¼ 19) or non-danger-based (n ¼ 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n ¼ 26) and Civilian Controls (n ¼ 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R 2 ¼ 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R 2 ¼ 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context.
    Social Cognitive and Affective Neuroscience 09/2015; DOI:10.1093/scan/nsv102 · 7.37 Impact Factor
  • Source
    • "To take the example of PTSD, the interplay between hippocampal and amygdala connection with medial and orbital prefrontal cortex is centrally embedded in neural models of this disorder (Phelps 2006; Liberzon and Sripada 2007; Shin et al. 2007; Admon et al. 2013). The current finding of an area and lamina mismatch between the input sites from the amygdala and hippocampus is, therefore, relevant as it supports and informs those models that seek to distinguish hippocampal and amygdala interactions within prefrontal cortex in the predisposition and maintenance of PTSD (Admon et al. 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The projections from the amygdala and hippocampus (including subiculum and presubiculum) to prefrontal cortex were compared using anterograde tracers injected into macaque monkeys (Macaca fascicularis, Macaca mulatta). Almost all prefrontal areas were found to receive some amygdala inputs. These connections, which predominantly arose from the intermediate and magnocellular basal nucleus, were particularly dense in parts of the medial and orbital prefrontal cortex. Contralateral inputs were not, however, observed. The hippocampal projections to prefrontal areas were far more restricted, being confined to the ipsilateral medial and orbital prefrontal cortex (within areas 11, 13, 14, 24a, 32, and 25). These hippocampal projections principally arose from the subiculum, with the fornix providing the sole route. Thus, while the lateral prefrontal cortex essentially receives only amygdala inputs, the orbital prefrontal cortex receives both amygdala and hippocampal inputs, though these typically target different areas. Only in medial prefrontal cortex do direct inputs from both structures terminate in common sites. But, even when convergence occurs within an area, the projections predominantly terminate in different lamina (hippocampal inputs to layer III and amygdala inputs to layers I, II, and VI). The resulting segregation of prefrontal inputs could enable the parallel processing of different information types in prefrontal cortex. © The Author 2015. Published by Oxford University Press.
    Cerebral Cortex 02/2015; DOI:10.1093/cercor/bhv019 · 8.67 Impact Factor
  • Source
    • "Yet there does exist a parallel phenomenon that seems to function similarly, though in the opposite direction; that is, a salient adverse event (i.e. trauma) may result in lasting negative effects in a person's physical and mental life [60] [61] [62] [63] [64] [65] [66] [67]. The acquired nature of post-traumatic stress disorder (PTSD) and the observation that acute adverse events are capable of producing enduring detrimental brain changes are well-documented. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for "complete" mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.
    Current Drug Abuse Reviews 01/2015; 08(999). DOI:10.2174/1874473708666150107121331
Show more