Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues

Regier, Paul S.; Monge, Zachary A.; Franklin, Teresa R.; Wetherill, Reagan R.; Teitelman, Anne M.; Jagannathan, Kanchana; Suh, Jo‐Young; Wang, Ze; Young, Kimberly A.; Gawrysiak, Michael J.; Langleben, Daniel D.; Kampman, Kyle M.; O’Brien, Charles P.; Childress, Anna Rose

doi:10.1111/adb.12445

Cited by 28 publications

(33 citation statements)

References 60 publications

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“…67 Heighted mesolimbic response has also been found in response to drug-related and evocative cues in cocaine-dependent individuals reporting a history of emotional, physical and sexual abuse. 68 Consistent with preclinical evidence demonstrating that the therapeutic efficacy of naltrexone is associated with early adverse experiences, 29 we found that naltrexone modulated task-related activation in the mPFC, one key region associated with emotion dysregulation in both substance use disorders and adults with histories of childhood adversity, depending on the degree of abuse experienced.…”

Section: Discussionsupporting

confidence: 83%

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

Savulich¹,

Riccelli²,

Passamonti³

et al. 2017

European Neuropsychopharmacology

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Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n = 18, alcohol) and in combination with cocaine and/or opioid dependence (n = 21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n = 21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

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Section: Discussionsupporting

confidence: 83%

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

Savulich¹,

Riccelli²,

Passamonti³

et al. 2017

European Neuropsychopharmacology

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“…Indeed, recent data from our lab (Regier et al, 2016), suggests that CUD individuals with prior adversity (e.g., prior sexual, emotional, and physical abuse) have an enhanced response to evocative cues (i.e., cocaine, sexual, and aversive) in mesolimbic motivational brain circuitry. Parallel results have been documented in aversively-motivated disorders (i.e., PTSD, generalized anxiety), in which there is enhanced amygdala reactivity to evocative cues (Patel et al, 2012; Shin and Liberzon, 2010).…”

Section: Discussionmentioning

confidence: 90%

“…Based on prior work (Regier et al, 2016), we further constrained the voxels that we queried in relation to the amygdala, based on a mask that includes mesolimbic regions (amygdala, ventral tegmental area/midbrain, ventral striatum, caudal orbitofrontal cortex), and three other addiction-relevant regions including the insula (Naqvi and Bechara, 2010), dorsal striatum (Everitt and Robbins, 2013), and thalamus (Asensio et al, 2010). The mask including our a priori ROIs, was created using Harvard-Oxford Cortical Structural Atlas (FMRI of the Brain [FMRIB] Software Library, Oxford Centre for FMIRB) with a probability threshold ranging between 10–25%.…”

Section: Methodsmentioning

confidence: 99%

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

Gawrysiak

Jagannathan

Regier

et al. 2017

Drug and Alcohol Dependence

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Background Substance use disorder (SUD) patients with a history of trauma exhibit poorer treatment outcome, greater functional impairment and higher risk for relapse. Endorsement of prior trauma has, in several SUD populations, been linked to abnormal functional connectivity (FC) during task-based studies. We examined amygdala FC in the resting state (RS), testing for differences between cocaine patients with and without prior trauma. Methods Patients with cocaine use disorder (CUD; n=34) were stabilized in an inpatient setting prior to a BOLD fMRI scan. Responses to Addiction Severity Index and the Mini-International Neuropsychiatric Interview were used to characterize the No-Trauma (n=16) and Trauma (n=18) groups. Seed-based RSFC was conducted using the right and left amygdala as regions of interest. Examination of amygdala RSFC was restricted to an a priori anatomical mask that incorporated nodes of the limbic-striatal motivational network. Results RSFC was compared for the Trauma versus No-Trauma groups. The Trauma group evidenced greater connectivity between the amygdala and the a priori limbic-striatal mask. Peaks within the statistically significant limbic-striatal mask included the amygdala, putamen, pallidum, caudate, thalamus, insula, hippocampus/parahippocampus, and brain stem. Conclusions Results suggest that cocaine patients with prior trauma (versus without) have heightened communication within nodes of the motivational network, even at rest. To our knowledge, this is the first fMRI study to examine amygdala RSFC among those with CUD and trauma history. Heightened RSFC intralimbic connectivity for the Trauma group may reflect a relapse-relevant brain vulnerability and a novel treatment target for this clinically-challenging population.

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“…Unprotected). Primary analyses were limited to subcortical regions [e.g., caudate, putamen, insula, amygdala, hippocampus, caudal orbitofrontal cortex (e.g., ventrolateral prefrontal cortex, or vlPFC), thalamus] associated with neural responses to sexual stimuli (Mitricheva et al, 2019) and other evocative cues (Childress et al, 1999;Franklin 1 http://www.fil.ion.ucl.ac.uk/spm Noori et al, 2016;Regier et al, 2017). These regions were combined into a mesolimbic ''cue-reactive'' mask ( Figure 1) using the Harvard-Oxford probabilistic anatomical atlas included with FMRIB Software Library (FSL).…”

Section: Mesolimbic ''Cue-reactive'' Maskmentioning

confidence: 99%

Women at Greater Sexual Risk for STIs/HIV Have a Lower Mesolimbic and Affective Bias Response to Sexual Stimuli

Regier

Teitelman

Jagannathan

et al. 2020

Front. Behav. Neurosci.

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Young adult women in the United States have high rates of sexually transmitted infections, increasing the risk of human immunodeficiency virus (HIV). The underlying neurobiology of behaviors that increase the probability of contracting sexuallytransmitted diseases (STIs) and HIV is just beginning to be explored. The current study assessed the link between sexual risk and the brain and behavioral response to sexual cues in emerging adult women. Our hypothesis was that women with more activity in reward/motivational circuitry would report higher sexual risk behaviors and would evidence higher positive affective bias to visual sexual stimuli. Women (n = 52; age = 18-24 years) who had protected sex 100% of the time (n = 17) vs. those who did not (n = 35), in the past 3 months, were compared on their brain response to 500 ms evocative (sex, aversive, food) vs. neutral cues in a blood-oxygen-leveldependent (BOLD) functional magnetic resonance imaging (fMRI) fast event-related design. Based on existing literature, an a priori anatomical "cue-reactive" mask was used to constrain the analyses. Self-reported sexual activity and the affective bias scores to sexual cues were examined as correlates with the brain response to cues. In contrast to our initial hypothesis, the higher sexual risk (Unprotected) group had significantly less activation in mesolimbic brain regions and lower (less positive) affective bias scores to sexual cues compared to the lower risk (Protected) group. As predicted, the brain response was positively correlated with sexual bias. Follow-up analyses showed an effect of partner "risk" (e.g., more vs. less knowledge of partner's STIs/HIV status). This evidence suggests that women who have protected sex may view sexual-related stimuli more positively, reflected by a neural response in reward/motivational regions and more positive sexual bias scores. In contrast, young women at increased risk for STIs/HIV may feel more negatively about sexual-related stimuli, evidenced by a lower mesolimbic response and a less positive affective bias to sexual cues. These data may help identify young women who are at greatest risk for acquiring STIs and/or HIV, which carries added importance with the availability of new medications that can prevent HIV.

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Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues

Cited by 28 publications

References 60 publications

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

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

Women at Greater Sexual Risk for STIs/HIV Have a Lower Mesolimbic and Affective Bias Response to Sexual Stimuli

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