22.2 WHAT DO BRAIN STRUCTURES ASSOCIATED WITH EXTINCTION LEARNING HAVE TO DO WITH POSTTRAUMATIC STRESS DISORDER AND LATER ADDICTIONS?

Author(s):  
Michael DeBellis
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanchao Zheng ◽  
Melanie E. Garrett ◽  
Delin Sun ◽  
Emily K. Clarke-Rubright ◽  
Courtney C. Haswell ◽  
...  

AbstractThe volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10−20), thalamus (p = 7.46 × 10−10), caudate (p = 1.97 × 10−18), putamen (p = 1.7 × 10−12), and nucleus accumbens (p = 1.99 × 10−7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = −0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p < 1 × 10−19) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10−7) or PTSD (rs10861272; p = 1.78 × 10−6) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.


2021 ◽  
Vol 53 (8S) ◽  
pp. 303-304
Author(s):  
Kevin M. Crombie ◽  
Anneliis Sartin-Tarm ◽  
Kyrie Sellnow ◽  
Rachel Ahrenholtz ◽  
Sierra Lee ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
M. L. Brandão ◽  
T. A. Lovick

Abstract In susceptible individuals, exposure to intensely traumatic life events can lead to the development of posttraumatic stress disorder (PTSD), including long-term dysregulation of the contextual processing of aversive stimuli, the overgeneralization of learned fear, and impairments in the ability to learn or respond to safety signals. The neuropathophysiological changes that underlie PTSD remain incompletely understood. Attention has focused on forebrain structures associated with fear processing. Here we consider evidence from human and animal studies that long-lasting changes in functional connectivity between the midbrain periaqueductal gray (dPAG) and amygdala may be one of the precipitating events that contribute to PTSD. Long-lasting neuroplastic changes in the dPAG can persist after a single aversive stimulation and are pharmacologically labile. The early stage (at least up to 24 h post-stimulation) involves neurokinin-1 receptor-mediated events in the PAG and amygdala and is also regulated by dopamine, both of which are mainly involved in transferring ascending aversive information from the dPAG to higher brain structures, mainly the amygdala. Changes in the functional connectivity within the dPAG-amygdala circuit have been reported in PTSD patients. We suggest that further investigations of plasticity and pharmacology of the PAG-amygdala network provide a promising target for understanding pathophysiological circuitry that underlies PTSD in humans and that dopaminergic and neurokininergic drugs may have a potential for the treatment of psychiatric disorders that are associated with a dysfunctional dPAG.


2002 ◽  
Vol 52 (11) ◽  
pp. 1066-1078 ◽  
Author(s):  
Michael D. De Bellis ◽  
Matcheri S. Keshavan ◽  
Heather Shifflett ◽  
Satish Iyengar ◽  
Sue R. Beers ◽  
...  

2021 ◽  
pp. 103867
Author(s):  
Kevin M. Crombie ◽  
Anneliis Sartin-Tarm ◽  
Kyrie Sellnow ◽  
Rachel Ahrenholtz ◽  
Sierra Lee ◽  
...  

2019 ◽  
Vol 50 (9) ◽  
pp. 1442-1451 ◽  
Author(s):  
Benjamin Suarez-Jimenez ◽  
Anton Albajes-Eizagirre ◽  
Amit Lazarov ◽  
Xi Zhu ◽  
Ben J. Harrison ◽  
...  

AbstractBackgroundEstablishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers.MethodsHere, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-basedd-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall.ResultsPatients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis.ConclusionFindings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Josh M. Cisler ◽  
Anthony A. Privratsky ◽  
Anneliis Sartin-Tarm ◽  
Kyrie Sellnow ◽  
Marisa Ross ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mayuresh S. Korgaonkar ◽  
Kim L. Felmingham ◽  
Aleksandra Klimova ◽  
May Erlinger ◽  
Leanne M. Williams ◽  
...  

AbstractTrauma-focused cognitive behavior therapy (TF-CBT) is the gold standard treatment for posttraumatic stress disorder (PTSD), up to one-half of PTSD patients remain treatment non-responders. Although studies have used functional MRI to understand the neurobiology of treatment response, there is less understanding of the role of white matter brain structures in response to TF-CBT. Thirty-six treatment-seeking PTSD patients and 33 age-gender matched healthy controls completed diffusion-weighted imaging scans at baseline. Patients underwent nine sessions of TF-CBT treatment and PTSD symptom severity was assessed with the Clinician-Administered PTSD Scale before and after completing treatment. Patients were assessed to estimate the reduction in overall symptoms and also specifically fear and dysphoric symptoms of PTSD. Tract-based spatial statistical analyses were performed for the PTSD group to evaluate whole-brain correlations of fractional anisotropy (FA) with improvement in overall, fear, and dysphoric symptoms using non-parametric permutation inference testing (pFWE < 0.05). Next, we evaluated if these significant measures also characterized PTSD from controls. Greater improvement in dysphoric symptoms was found correlated with lower FA in white matter regions associated with the limbic system, frontal cortex, thalamic association and projection fibers, corpus callosum, and tracts related to the brainstem. White matter anisotropy was not found associated with either overall or fear symptoms. FA in the significant clusters was similar between PTSD and controls. White-matter related to key functional regions may also play an important role in response to TF-CBT. Our results underscore the heterogeneity of PTSD and the need to evaluate distinct symptom phenotypes in treatment studies.


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