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Neural mechanisms and predictors of SSRI and CBT treatment of anxiety: A randomized trial focused on emotion and cognitive processing.

ABSTRACT: Anxiety disorders (ADs) are common and difficult to treat. While research suggests ADs are characterized by an imbalance between bottom-up and top-down attention processes and that effective treatments work by correcting this dysfunction, there is insufficient data to explain how and for whom treatments work. The late positive potential (LPP), an event-related potential reflecting elaborative processing of motivationally salient stimuli, is sensitive to both bottom-up and top-down processes. The present study examines the LPP in healthy controls (HC) and patients with ADs under low and high working memory (WM) load to assess its utility as a predictor and index of symptom reduction in patients who underwent cognitive behavioral therapy (CBT) or selective serotonin reuptake inhibitor (SSRI) treatment. The LPP when viewing negative and neutral distractor images and WM performance were assessed in 96 participants (40 HC, 32 CBT, 24 SSRI) during a letter recall task at Week 0 and in a subset of the study sample (23 CBT, 16 SSRI) at Week 12. Patients were randomly assigned to twelve weeks of CBT or SSRI treatment. Participants completed self-reported symptom measures at each time point. Greater Week 0 LPP to negative images under low WM load predicted greater symptom reduction in the SSRI, but not the CBT, group. Regression analyses examining the LPP to negative images as an index of symptom reduction revealed a smaller decrease in the LPP to negative images under low WM load was associated with less anxiety reduction across treatment modalities. Findings suggest the LPP during low WM load may serve as a cost-effective predictor and index of treatment outcome in ADs. Clinical Trials Registration: ClinicalTrials.gov (Identifier: NCT01903447).

SUBMITTER: Kinney KL

PROVIDER: S-EPMC8364887 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Neural mechanisms and predictors of SSRI and CBT treatment of anxiety: A randomized trial focused on emotion and cognitive processing.

Kinney Kerry L KL Burkhouse Katie L KL Chang Fini F MacNamara Annmarie A Klumpp Heide H Phan K Luan KL

Journal of anxiety disorders 20210710

Anxiety disorders (ADs) are common and difficult to treat. While research suggests ADs are characterized by an imbalance between bottom-up and top-down attention processes and that effective treatments work by correcting this dysfunction, there is insufficient data to explain how and for whom treatments work. The late positive potential (LPP), an event-related potential reflecting elaborative processing of motivationally salient stimuli, is sensitive to both bottom-up and top-down processes. The ...[more]

PMID: 34274600

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Project description:ImportancePsychiatric comorbidity complicates clinical care and confounds efforts to elucidate the pathophysiology of commonly occurring symptoms in youths. To our knowledge, few studies have simultaneously assessed the effect of 2 continuously distributed traits on brain-behavior relationships in children with psychopathology.ObjectiveTo determine shared and unique effects of 2 major dimensions of child psychopathology, irritability and anxiety, on neural responses to facial emotions during functional magnetic resonance imaging.Design, setting, and participantsCross-sectional functional magnetic resonance imaging study in a large, well-characterized clinical sample at a research clinic at the National Institute of Mental Health. The referred sample included youths ages 8 to 17 years, 93 youths with anxiety, disruptive mood dysregulation, and/or attention-deficit/hyperactivity disorders and 22 healthy youths.Main outcomes and measuresThe child's irritability and anxiety were rated by both parent and child on the Affective Reactivity Index and Screen for Child Anxiety Related Disorders, respectively. Using functional magnetic resonance imaging, neural response was measured across the brain during gender labeling of varying intensities of angry, happy, or fearful face emotions. In mixed-effects analyses, the shared and unique effects of irritability and anxiety were tested on amygdala functional connectivity and activation to face emotions.ResultsThe mean (SD) age of participants was 13.2 (2.6) years; of the 115 included, 64 were male. Irritability and/or anxiety influenced amygdala connectivity to the prefrontal and temporal cortex. Specifically, irritability and anxiety jointly influenced left amygdala to left medial prefrontal cortex connectivity during face emotion viewing (F4,888 = 9.20; P < .001 for mixed model term). During viewing of intensely angry faces, decreased connectivity was associated with high levels of both anxiety and irritability, whereas increased connectivity was associated with high levels of anxiety but low levels of irritability (Wald χ21 = 21.3; P < .001 for contrast). Irritability was associated with differences in neural response to face emotions in several areas (F2, 888 ≥ 13.45; all P < .001). This primarily occurred in the ventral visual areas, with a positive association to angry and happy faces relative to fearful faces.Conclusions and relevanceThese data extend prior work conducted in youths with irritability or anxiety alone and suggest that research may miss important findings if the pathophysiology of irritability and anxiety are studied in isolation. Decreased amygdala-medial prefrontal cortex connectivity may mediate emotion dysregulation when very anxious and irritable youth process threat-related faces. Activation in the ventral visual circuitry suggests a mechanism through which signals of social approach (ie, happy and angry expressions) may capture attention in irritable youth.

Dataset Information

Neural mechanisms and predictors of SSRI and CBT treatment of anxiety: A randomized trial focused on emotion and cognitive processing.

Publications

Neural mechanisms and predictors of SSRI and CBT treatment of anxiety: A randomized trial focused on emotion and cognitive processing.

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