Unseen scars: Cocaine patients with prior trauma evidence heightened resting state functional connectivity (RSFC) between the amygdala and limbic-striatal regions

Gawrysiak, Michael J.; Jagannathan, Kanchana; Regier, Paul S.; Suh, Jo‐Young; Kampman, Kyle M.; Vickery, Timothy J.; Childress, Anna Rose

doi:10.1016/j.drugalcdep.2017.08.035

Cited by 10 publications

(9 citation statements)

References 91 publications

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“…In addition, stronger connectivity between the amygdala and limbic circuitry, including the striatum, is observed in patients with cocaine use disorder 43–44 . Finally, prior trauma in individuals with a cocaine use disorder has been found to enhance amygdala‐striatal connectivity both at resting state 45 and in response to cocaine cues 46 . An important focus of future studies will be to further dissect the specific neural circuitry driving cue‐ and chronic stress‐induced changes in cocaine seeking and relapse vulnerability.…”

Section: Discussionmentioning

confidence: 99%

Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala

et al. 2019

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Cocaine addiction is a chronic, relapsing disorder. Stress and cues related to cocaine are two common relapse triggers. We have recently shown that exposure to repeated restraint stress during early withdrawal accelerates the time-dependent intensification or "incubation" of cue-induced cocaine craving that occurs during the first month of withdrawal, although craving ultimately plateaus at the same level observed in controls. These data indicate that chronic stress exposure during early withdrawal may result in increased vulnerability to cue-induced relapse during this period. Previous studies have shown that chronic stress exposure in drug-naïve rats increases neuronal activity in the basolateral amygdala (BLA), a region critical for behavioral responses to stress. Given that glutamatergic projections from the BLA to the nucleus accumbens are critical for the incubation of cue-induced cocaine craving, we hypothesized that cocaine withdrawal and chronic stress exposure produce separate increases that additively increase BLA neuronal activity. To assess this, we conducted in vivo extracellular single-unit recordings from the BLA of anesthetized adult male rats following cocaine or saline self-administration (6 h/day for 10 days) and repeated restraint stress or control conditions on withdrawal days (WD) 6-14. Recordings were conducted from WD15 to WD20. Interestingly, cocaine exposure alone increased the spontaneous firing rate in the BLA to levels observed following chronic stress exposure in drug-naïve rats. Chronic stress exposure during cocaine withdrawal further increased firing rate. These studies may identify a potential mechanism by which both cocaine and chronic stress exposure drive cue-induced relapse vulnerability during abstinence.

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Section: Discussionmentioning

confidence: 99%

Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala

et al. 2019

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“…Sex differences were examined in only one RSFC study (7) and revealed greater connectivity between the medial hypothalamus and a critical node of the default mode network, the precuneus, in female cocaine users compared to males. A recent study has also examined modulation of RSFC by history of childhood trauma in CUD (18). The CUD group reported that some childhood trauma showed greater amygdala RSFC with several striatal regions, the insula, medial temporal regions, and the brain stem.…”

Section: Introductionmentioning

confidence: 99%

Oxytocin-Induced Changes in Intrinsic Network Connectivity in Cocaine Use Disorder: Modulation by Gender, Childhood Trauma, and Years of Use

et al. 2019

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Cocaine use disorder (CUD) is a major public health concern with devastating social, economic, and mental health implications. A better understanding of the underlying neurobiology and phenotypic variations in individuals with CUD is necessary for the development of effective and targeted treatments. In this study, 39 women and 54 men with CUD completed a 6-min resting-state functional magnetic resonance imaging scan after intranasal oxytocin (OXY) or placebo administration. Graph-theory network analysis was used to quantify functional connectivity changes caused by OXY in striatum, anterior cingulate cortex (ACC), insula, and amygdala nodes of interest. OXY increased connectivity in the right ACC and left amygdala in males, whereas OXY increased connectivity in the right ACC and right accumbens in females. Machine learning was then used to associate treatment response (placebo minus OXY) in nodes of interest with years of cocaine use and severity of childhood trauma separately for males and females. Childhood trauma and years of cocaine use were associated with OXY-induced changes in ACC connectivity for both men and women, but connectivity changes in the amygdala were associated with years of cocaine use in men and connectivity changes in the right insula were associated with years of cocaine use in women. These findings suggest that salience network nodes (ACC and insula) are potential OXY treatment targets in CUD, with the amygdala as a treatment target for men and the accumbens as a treatment target for women.

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“…The evaluation of comorbid cocaine use disorder and PTSD has garnered valuable insights into the overlapping symptomatology and shared neurobiologic etiology of these comorbid disorders [ 48 , 49 ]. Gawrysiak et al conducted BOLD fMRI scans in 34 treatment-seeking men admitted for cocaine use disorder with and without trauma after 7–10 days of supervised sobriety [ 50 ]. Individuals with cocaine use disorder and trauma showed greater functional connectivity between the amygdala and limbic-striatal regions, including nodes of mesolimbic motivational circuitry in the caudate nucleus, putamen, pallidum, and insula, compared to individuals without trauma [ 50 ].…”

Section: Lessons From Translational and Clinical Researchmentioning

confidence: 99%

“…Gawrysiak et al conducted BOLD fMRI scans in 34 treatment-seeking men admitted for cocaine use disorder with and without trauma after 7–10 days of supervised sobriety [ 50 ]. Individuals with cocaine use disorder and trauma showed greater functional connectivity between the amygdala and limbic-striatal regions, including nodes of mesolimbic motivational circuitry in the caudate nucleus, putamen, pallidum, and insula, compared to individuals without trauma [ 50 ]. The authors propose this heightened state of connectivity may predispose individuals with trauma to increased reactivity to drug-related cues [ 50 ].…”

Section: Lessons From Translational and Clinical Researchmentioning

confidence: 99%

Elucidating the Neurobiologic Etiology of Comorbid PTSD and Substance Use Disorders

Hinckley

Danielson

2022

Brain Sciences

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Early childhood maltreatment and other traumatic event experiences (“trauma”) are common among youth, including those with substance use problems including substance use disorders (SUD). Particularly, interpersonal violence is associated with high rates of comorbidity between posttraumatic stress disorder (PTSD) and SUD, and these comorbid disorders exhibit high levels of overlapping symptomatology. Theoretical models proposed to explain the bidirectional relationship between PTSD and SUD include the self-medication hypothesis and susceptibility hypothesis. In this article, we explore neurobiologic changes associated with trauma, PTSD, and SUD that underly dysregulated stress response. Examining lessons learned from recent translational and clinical research, we propose that further elucidating the neurobiologic etiology of comorbid PTSD and SUD will require a collaborative, interdisciplinary approach, including the integration of preclinical and clinical studies, exploration of biologic markers in clinical studies, and accumulation of larger studies and longitudinal studies with the power to study PTSD and SUD. Such research can transform the field and ultimately reduce high rates and costly impairment of co-occurring PTSD and SUD across the lifespan.

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Unseen scars: Cocaine patients with prior trauma evidence heightened resting state functional connectivity (RSFC) between the amygdala and limbic-striatal regions

Cited by 10 publications

References 91 publications

Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala

Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala

Oxytocin-Induced Changes in Intrinsic Network Connectivity in Cocaine Use Disorder: Modulation by Gender, Childhood Trauma, and Years of Use

Elucidating the Neurobiologic Etiology of Comorbid PTSD and Substance Use Disorders

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