OBJECTIVE: Amygdala-ventrolateral prefrontal cortex (VLPFC) circuitry is disrupted in pediatric anxiety disorders, yet how selective serotonin reuptake inhibitors (SSRIs) affect this circuitry is unknown. We examined the impact of the SSRI escitalopram on functional connectivity (FC) within this circuit, and whether early FC changes predicted treatment response in adolescents with generalized anxiety disorder (GAD). METHOD: Resting-state functional magnetic resonance (MR) images were acquired before and after 2 weeks of treatment in 41 adolescents with GAD (12-17 years of age) who received double-blind escitalopram or placebo for 8 weeks. Change in amygdala-based whole-brain FC and anxiety severity were analyzed. RESULTS: Controlling for age, sex, and pretreatment anxiety, escitalopram increased amygdala-VLPFC connectivity compared to placebo (F = 17.79, p = .002 FWE-corrected). This early FC change predicted 76.7% of the variability in improvement trajectory in patients who received escitalopram (p < .001) but not placebo (p = .169); the predictive power of early amygdala-VLPFC FC change significantly differed between placebo and escitalopram (p = .013). Furthermore, this FC change predicted improvement better than baseline FC or clinical/demographic characteristics. Exploratory analyses of amygdala subfields' FC revealed connectivity of left basolateral amygdala (BLA) -VLPFC (F = 19.64, p < .001 FWE-corrected) and superficial amygdala-posterior cingulate cortex (F = 22.92, p = .001 FWE-corrected) were also increased by escitalopram, but only BLA-VLPFC FC predicted improvement in anxiety over 8 weeks of treatment. CONCLUSION: In adolescents with GAD, escitalopram increased amygdala-prefrontal connectivity within the first 2 weeks of treatment, and the magnitude of this change predicted subsequent clinical improvement. Early normalization of amygdala-VLPFC circuitry might represent a useful tool for identifying future treatment responders as well as a promising biomarker for drug development. CLINICAL TRIAL REGISTRATION INFORMATION: Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety; https://www.clinicaltrials.gov/; NCT02818751.
OBJECTIVE: Amygdala-ventrolateral prefrontal cortex (VLPFC) circuitry is disrupted in pediatric anxiety disorders, yet how selective serotonin reuptake inhibitors (SSRIs) affect this circuitry is unknown. We examined the impact of the SSRI escitalopram on functional connectivity (FC) within this circuit, and whether early FC changes predicted treatment response in adolescents with generalized anxiety disorder (GAD). METHOD: Resting-state functional magnetic resonance (MR) images were acquired before and after 2 weeks of treatment in 41 adolescents with GAD (12-17 years of age) who received double-blind escitalopram or placebo for 8 weeks. Change in amygdala-based whole-brain FC and anxiety severity were analyzed. RESULTS: Controlling for age, sex, and pretreatment anxiety, escitalopram increased amygdala-VLPFC connectivity compared to placebo (F = 17.79, p = .002 FWE-corrected). This early FC change predicted 76.7% of the variability in improvement trajectory in patients who received escitalopram (p < .001) but not placebo (p = .169); the predictive power of early amygdala-VLPFC FC change significantly differed between placebo and escitalopram (p = .013). Furthermore, this FC change predicted improvement better than baseline FC or clinical/demographic characteristics. Exploratory analyses of amygdala subfields' FC revealed connectivity of left basolateral amygdala (BLA) -VLPFC (F = 19.64, p < .001 FWE-corrected) and superficial amygdala-posterior cingulate cortex (F = 22.92, p = .001 FWE-corrected) were also increased by escitalopram, but only BLA-VLPFC FC predicted improvement in anxiety over 8 weeks of treatment. CONCLUSION: In adolescents with GAD, escitalopram increased amygdala-prefrontal connectivity within the first 2 weeks of treatment, and the magnitude of this change predicted subsequent clinical improvement. Early normalization of amygdala-VLPFC circuitry might represent a useful tool for identifying future treatment responders as well as a promising biomarker for drug development. CLINICAL TRIAL REGISTRATION INFORMATION: Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety; https://www.clinicaltrials.gov/; NCT02818751.
Authors: Chad M Sylvester; Qiongru Yu; A Benjamin Srivastava; Scott Marek; Annie Zheng; Dimitrios Alexopoulos; Christopher D Smyser; Joshua S Shimony; Mario Ortega; Donna L Dierker; Gaurav H Patel; Steven M Nelson; Adrian W Gilmore; Kathleen B McDermott; Jeffrey J Berg; Andrew T Drysdale; Michael T Perino; Abraham Z Snyder; Ryan V Raut; Timothy O Laumann; Evan M Gordon; Deanna M Barch; Cynthia E Rogers; Deanna J Greene; Marcus E Raichle; Nico U F Dosenbach Journal: Proc Natl Acad Sci U S A Date: 2020-02-03 Impact factor: 11.205
Authors: Jeffrey R Strawn; Eric T Dobson; Jeffrey A Mills; Gary J Cornwall; Dara Sakolsky; Boris Birmaher; Scott N Compton; John Piacentini; James T McCracken; Golda S Ginsburg; Phillip C Kendall; John T Walkup; Anne Marie Albano; Moira A Rynn Journal: J Child Adolesc Psychopharmacol Date: 2017-04-06 Impact factor: 2.576
Authors: Christopher S Monk; Eva H Telzer; Karin Mogg; Brendan P Bradley; Xiaoqin Mai; Hugo M C Louro; Gang Chen; Erin B McClure-Tone; Monique Ernst; Daniel S Pine Journal: Arch Gen Psychiatry Date: 2008-05
Authors: Paul J Whalen; Tom Johnstone; Leah H Somerville; Jack B Nitschke; Sara Polis; Andrew L Alexander; Richard J Davidson; Ned H Kalin Journal: Biol Psychiatry Date: 2007-10-26 Impact factor: 13.382
Authors: Alan N Simmons; Estibaliz Arce; Kathryn L Lovero; Murray B Stein; Martin P Paulus Journal: Int J Neuropsychopharmacol Date: 2009-06-23 Impact factor: 5.176
Authors: Stacey L Aldrich; Ethan A Poweleit; Cynthia A Prows; Lisa J Martin; Jeffrey R Strawn; Laura B Ramsey Journal: Front Pharmacol Date: 2019-02-19 Impact factor: 5.810
Authors: Marco Bocchio; Stephen B McHugh; David M Bannerman; Trevor Sharp; Marco Capogna Journal: Front Neural Circuits Date: 2016-04-05 Impact factor: 3.492
Authors: Duncan C Honeycutt; Melissa P DelBello; Jeffrey R Strawn; Laura B Ramsey; Luis R Patino; Kyle Hinman; Jeffrey Welge; David J Miklowitz; Booil Jo; Thomas J Blom; Kaitlyn M Bruns; Sarah K Hamill Skoch; Nicole Starace; Maxwell J Tallman; Manpreet K Singh Journal: J Pers Med Date: 2022-06-20
Authors: W Thomas Baumel; Jeffrey A Mills; Heidi K Schroeder; Ashley M Specht; Richard Rothenberg; Tara S Peris; Jeffrey R Strawn Journal: J Child Adolesc Psychopharmacol Date: 2022-05-09 Impact factor: 3.031
Authors: Lu Lu; Hailong Li; William T Baumel; Jeffrey A Mills; Kim M Cecil; Heidi K Schroeder; Sarah A Mossman; Xiaoqi Huang; Qiyong Gong; John A Sweeney; Jeffrey R Strawn Journal: Neuropsychopharmacology Date: 2021-09-27 Impact factor: 8.294
Authors: W Tommy Baumel; Lu Lu; Xiaoqi Huang; Andrew T Drysdale; John A Sweeny; Qiyong Gong; Chad M Sylvester; Jeffrey R Strawn Journal: Biomark Neuropsychiatry Date: 2022-04-22
Authors: Bhedita J Seewoo; Jennifer Rodger; Mark A Demitrack; Karen L Heart; John D Port; Jeffrey R Strawn; Paul E Croarkin Journal: Int J Neuropsychopharmacol Date: 2022-08-16 Impact factor: 5.678