Acute Neurofunctional Effects of Escitalopram in Pediatric Anxiety: A Double-Blind, Placebo-Controlled Trial

Lu, Lu; Mills, Jeffrey A.; Li, Hailong; Schroeder, Heidi K.; Mossman, Sarah A.; Varney, Sara T.; Cecil, Kim M.; Huang, Xiaoqi; Gong, Qiyong; Ramsey, Laura B.; DelBello, Melissa P.; Sweeney, John A.

doi:10.1016/j.jaac.2020.11.023

Cited by 19 publications

(9 citation statements)

References 55 publications

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“…One study has examined treatment-related changes in functional connectivity in adolescents with GAD ( N = 41, mean age: 15 ± 1.7 years) ( Lu et al, 2021 ). In the study, adolescents were randomized to escitalopram or placebo.…”

Section: Resultsmentioning

confidence: 99%

“…During the first 2 weeks of treatment, escitalopram – but not placebo – increased amygdala-vlPFC connectivity. This early functional connectivity change predicted symptom improvement over the subsequent 6 weeks of treatment in youth who received escitalopram, but not in those who received placebo ( Lu et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…We choose this for a case example as amygdala connectivity has been widely implicated and well-characterized across anxiety disorders ( McTeague et al, 2020 ; Sylvester et al, 2020 ). Seven studies have examined the treatment-related effects on amygdala to whole brain functional connectivity ( Brown et al, 2019 ; Fonzo et al, 2014 ; Lu et al, 2021 ; Månsson et al, 2013 ; Reinecke et al, 2018 ; Young et al, 2017 ; Yuan et al, 2016 ). Of these, three use a sample of patients with social anxiety disorder, one uses a sample of patients with panic disorder, and two use a sample of patients with generalized anxiety disorder, one of which utilized a pediatric population and is the only pharmacotherapy study.…”

Section: Discussionmentioning

confidence: 99%

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Neurocircuitry of treatment in anxiety disorders

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Huang

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Biomarkers in Neuropsychiatry

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Neurocircuitry of treatment in anxiety disorders

Baumel

Huang

et al. 2022

Biomarkers in Neuropsychiatry

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“…Depressed participants were recruited from within the clinics and via referrals from other care providers. Depressed and healthy participants were recruited with radio advertisements, invitation letters sent to parents of potentially eligible participants, print advertisements, a trial listing with ClinicalTrials.gov, a trial listing on university and clinical study site website, and social media ( Wall et al, 2016 ; Croarkin et al, 2016 , 2021 ; Lewis et al, 2016 ; Lu et al 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Neurostructural Differences in Adolescents With Treatment-Resistant Depression and Treatment Effects of Transcranial Magnetic Stimulation

Seewoo

Rodger

Demitrack

et al. 2022

International Journal of Neuropsychopharmacology

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Background Despite its morbidity and mortality, the neurobiology of treatment resistant depression (TRD) in adolescents and the impact of treatment on this neurobiology is poorly understood. Methods Using automatic segmentation in FreeSurfer, we examined brain magnetic resonance imaging (MRI) baseline volumetric differences among healthy adolescents (n=30), adolescents with major depressive disorder (MDD) (n=19), and adolescents with TRD (n=34) based on objective antidepressant treatment rating criteria. A pooled subsample of adolescents with TRD were treated with six weeks of active (n=18) or sham (n=7) 10 Hz transcranial magnetic stimulation (TMS) applied to the left dorsolateral prefrontal cortex (L-DLPFC). Ten of the adolescents treated with active TMS were part of an open-label trial. The other adolescents treated with active (n=8) or sham (n=7) were participants from a randomized controlled trial. Results Adolescents with TRD and adolescents with MDD had decreased total amygdala (TRD and MDD: -5%, p=0.032), and caudal anterior cingulate cortex volumes (TRD: -3%, p=0.030; MDD: -0.03%, p=0.041) compared to healthy adolescents. Six weeks of active TMS increased total amygdala volumes (+4%, p<0.001) and the volume of the stimulated L-DLPFC (+0.4%, p=0.026) in adolescents with TRD. Conclusions Amygdala volumes were reduced in this sample of adolescents with MDD and TRD. TMS may normalize this volumetric finding raising the possibility that TMS has neurostructural frontolimbic effects in adolescents with TRD. TMS also appears to have positive effects proximal to the site of stimulation.

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“…First-degree relatives will be assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) [ 83 ] and the Family History-Research Diagnostic Criteria (FH-RDC). We will also compare our findings to those of a recently published double-blind, placebo-controlled trial using the same neuroimaging task and the same medication, but in youth without a family history of BD [ 84 ].…”

Section: Study Protocolmentioning

confidence: 97%

A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder

Honeycutt

DelBello

Ramsey

et al. 2022

JPM

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Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12–17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.

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Acute Neurofunctional Effects of Escitalopram in Pediatric Anxiety: A Double-Blind, Placebo-Controlled Trial

Cited by 19 publications

References 55 publications

Neurocircuitry of treatment in anxiety disorders

Neurocircuitry of treatment in anxiety disorders

Neurostructural Differences in Adolescents With Treatment-Resistant Depression and Treatment Effects of Transcranial Magnetic Stimulation

A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder

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