Association of Neural Reward Circuitry Function With Response to Psychotherapy in Youths With Anxiety Disorders

Sequeira, Stefanie; Silk, Jennifer S.; Ladouceur, Cecile D.; Hanson, Jamie L.; Ryan, Neal D.; Morgan, Judith K.; McMakin, Dana L.; Kendall, Philip C.; Dahl, Ronald E.; Forbes, Erika E.

doi:10.1176/appi.ajp.2020.20010094

Cited by 28 publications

(17 citation statements)

References 44 publications

(52 reference statements)

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“…Namely, those individuals with a more intact neural response to rewards (relative to the other anhedonic adolescents in the sample) experienced better BA outcomes. These findings are generally consistent with several prior studies supporting a capitalization model [16,[52][53][54][55], but not with other research supporting a compensatory model [49][50][51]. However, given the substantial differences between the latter studies and the present study in sample (e.g., adults with depression or anxiety vs. anhedonic adolescents), imaging modality (e.g., EEG vs. fMRI), task (each used a different reward task) and intervention delivered (e.g., CBT, SSRI, or BA), it is very challenging to determine which study features contributed to the differences in findings.…”

Section: Discussionsupporting

confidence: 92%

“…In contrast, other CBT studies [16,52,53], a trial of CBT vs. supportive therapy [54], as well as one study of the transdiagnostic Unified Protocol [55] yielded findings consistent with a capitalization model, such that patients who received a treatment matched to their relative strengths had the best outcomes. Notably, of the abovementioned studies that tested pretreatment neural predictors of treatment outcome, all found evidence of neural response to rewarding outcomes predicting symptom improvement [16,50,51,54]. Informed by these prior findings, we tested whether baseline self-report (ecological momentary assessment; EMA), neural and behavioral reward measures predicted improvement in anhedonia among anhedonic adolescents receiving BA.…”

Section: The Present Studymentioning

confidence: 87%

“…Of relevance, two electroencephalogram (EEG) studies in adults with anxiety and/or depression reported that blunted pre-treatment neural response to rewarding outcomes (but not the anticipation of rewards [50]) predicted greater depressive symptom improvement to CBT [50] and SSRI [51]. In contrast, other CBT studies [16,52,53], a trial of CBT vs. supportive therapy [54], as well as one study of the transdiagnostic Unified Protocol [55] yielded findings consistent with a capitalization model, such that patients who received a treatment matched to their relative strengths had the best outcomes. Notably, of the abovementioned studies that tested pretreatment neural predictors of treatment outcome, all found evidence of neural response to rewarding outcomes predicting symptom improvement [16,50,51,54].…”

Section: The Present Studymentioning

confidence: 99%

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Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach

Webb

Murray

Tierney

et al. 2022

Neuropsychopharmacol.

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Anhedonia is a cardinal characteristic of depression which predicts worse treatment outcome and is among the most common residual symptoms following treatment. Behavioral Activation (BA) has been shown to be an effective treatment for depressed adults, and more recently, depressed adolescents. Given its emphasis on systematically and gradually increasing exposure to and engagement with rewarding activities and experiences, BA may be a particularly effective intervention for adolescents experiencing anhedonia and associated reward system dysfunction.In the present study, anhedonic adolescents (AA; n = 39) received 12 weekly sessions of BA and completed a multimodal (i.e., neural, behavioral, and self-report [ecological momentary assessment]) assessment of reward function at pre-treatment and post-treatment (as well as weekly self-report assessments of anhedonia). Typically developing adolescents (TDA; n = 41) completed the same measures at corresponding timepoints. Multilevel models tested pretreatment reward-related predictors of anhedonia improvement, as well as change in reward measures over the course of BA. Analyses revealed significant reductions in anhedonia following BA treatment. Enhanced pre-treatment neural (striatal) reward responsiveness predicted greater anhedonia improvement. In contrast, baseline self-report and behavioral reward measures did not predict treatment outcome. A group x time interaction revealed greater increases in both reward-and loss-related neural responsiveness among AA relative to TDA adolescents. Consistent with a capitalization (rather than compensatory) model, pre-treatment neural -but not self-report or behavioral -measures of relatively enhanced reward responsiveness predicted better BA outcome. In addition to alleviating anhedonia, successful BA may also increase neural sensitivity to affectively salient (e.g., reward-and loss-related) stimuli among anhedonic youth.

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Section: Discussionsupporting

confidence: 92%

Section: The Present Studymentioning

confidence: 87%

Section: The Present Studymentioning

confidence: 99%

See 1 more Smart Citation

Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach

Webb

Murray

Tierney

et al. 2022

Neuropsychopharmacol.

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“…Adverse outcomes might be particularly profound when elevated mesostriatal dopamine transmission is combined with reduced or asynchronous cortical dopamine function (Chaudhury et al, 2013;Duvarci et al, 2018;Leyton & Vezina, 2014). Indeed, across diagnostic categories, there is evidence of poorly regulated dopamine transmission (Buckholtz, Treadway, Cowan, Woodward, Benning, et al, 2010;Cherkasova et al, 2014;Jaworska et al, 2020;Sequeira et al, 2021;Vosberg et al, 2020;Wang et al, 2019) with DRD2 variants constituting a transdiagnostic risk gene (P. H. Lee et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

A three-factor model of common early onset psychiatric disorders: temperament, adversity, and dopamine

Iqbal

Cox

Jaworska

et al. 2021

Neuropsychopharmacol.

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The causes of psychiatric disorders are poorly understood. Recent models propose that many early onset disorders that are commonly comorbid might reflect the varying expression of overlapping risk factors. The mediating processes remain largely unknown, but three factors show some promise: adolescent externalizing traits, early life adversity, and midbrain dopamine D2 autoreceptors. To investigate whether these features acquire greater predictive power when combined, a longitudinal study was conducted in youth who have been followed since birth.Cohort members were invited to participate based on externalizing scores between 10 to 16 years of age. At age 18 (age 18.5 ± 0.6 y.o.), 52 volunteers who met the entry criteria had a 90-min positron emission tomography scan with [ 18 F]fallypride to image dopamine D2 autoreceptors, completed the Childhood Trauma Questionnaire, and were assessed with the Structured Clinical Interview for DSM-5. The three-factor model identified those with a lifetime history of DSM-5 disorders with an overall accuracy of 90.4% (p = 2.4 x 10 -5 ) and explained 91.5% of the area under the receiver operating characteristic curve [95% CI: .824, 1.000]. Targeting externalizing disorders specifically did not yield a more powerful model than targeting all disorders (p = 0.54).The model remained significant when including data from participants who developed their first disorders during a three-year follow-up period (p = 3.5 x 10 -5 ). Together, these results raise the possibility that a combination of temperamental traits, childhood adversity, and poorly regulated dopamine transmission increases risk for diverse, commonly comorbid, early onset psychiatric problems, predicting this susceptibility prospectively.

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“…NLRP3 cascade signaling and neuron injury in mPFC and stritaum occurred after binge drinking-induced anxiety-like behavior Having shown that NLRP3 de ciency decreases binge drinking-induced anxiety-like behavior, we asked about the speci c in ammatory response mechanism behind it. It is studied that the medial prefrontal cortex (mPFC) modulates anxiety behaviors [31], and the striatum has a close responsivity to reward [32]. Thus, slices and tissues from mPFC and striatum were prepared 6 h after the last alcohol exposure to detect neuron injury.…”

Section: Nlrp3 De Ciency Decreases Binge Drinking-induced Anxiety-lik...mentioning

confidence: 99%

NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in mPFC-striatal circuits

Vidjro

Guo

et al. 2022

Preprint

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Background Repeated binge alcohol drinking and chronic alcohol consumption with negative effects such as anxiety on cessation induces alcohol use disorders. This process is associated with activation of NLRP3 inflammasome-mediated responses. However, whether and how inhibition of NLRP3 inflammasome alters alcohol intake and anxiety behavior remains unclear. Methods A combination of drinking-in-the dark and Gavage model were established in NLRP3-knockout and their control mice. Behaviors were assessed by open-field and elevated plus maze tests. Binge alcohol drinking at 2h and 4h were measured and 24 voluntary drinking was determined by a two-bottle choice paradigm. Western blot and ELISA were applied to examine the levels of NLRP3 inflammasome and inflammatory factors such as IL-1β and TNF-α. Nissl’s staining was measured the neuronal injury. Electrophysiological method was determined the glutamatergic transmission in mPFC to striatum circuits. In vivo opotogenetic LTP and LTD were applied to control the function of mPFC-striatal circuits on behavior of mice. MCC950 was used to antagonize NLRP3 inflammasome. Results The binge alcohol intake was decreased in NLRP3 KO mice compared to their control drinking mice. During alcohol withdrawal, NLRP3 deficiency attenuated anxiety-like behaviors and neuronal injury in mPFC and striatum. Moreover, we discovered that the glutamatergic transmission from cortex to striatum was reduced in NLRP3 KO mice. Importantly, in vivo optogenetic induction of long-term potentiation (LTP) of mPFC-striatal circuits reversed the effects of NLRP3 deficiency on glutamatergic transmission and anxiety behaviors. We also demonstrated that optogenetic induction of LTD decreased anxiety-like behaviors with a reduction of glutamatergic transmission. Interestingly, NLRP3 deficiency or inhibition (MCC950 injection)-mediated the attenuation of anxiety behavior reduced binge alcohol intake, but did not decrease 24h-voluntary alcohol consumption and alcohol preference. Conclusion Our results demonstrate that NLRP3 deficiency decreases binge alcohol intake and anxiety-like behaviors through downregulation of glutamatergic transmission in mPFC-striatal circuits, which may provide an anti-inflammatory target to treat alcohol use disorders.

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Association of Neural Reward Circuitry Function With Response to Psychotherapy in Youths With Anxiety Disorders

Cited by 28 publications

References 44 publications

Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach

Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach

A three-factor model of common early onset psychiatric disorders: temperament, adversity, and dopamine

NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in mPFC-striatal circuits

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