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Anxiety disorders are the most common mental disorders in adolescents. However, only 50% of pediatric patients with anxiety disorders respond to the first-line pharmacologic treatments-selective serotonin reuptake inhibitors (SSRIs). Thus, identifying the neurofunctional targets of SSRIs and finding pretreatment or early-treatment neurofunctional markers of SSRI treatment response in this population is clinically important. We acquired pretreatment and early-treatment (2 weeks into treatment) functional magnetic resonance imaging during a continuous processing task with emotional and neutral distractors in adolescents with generalized anxiety disorder (GAD, N = 36) randomized to 8 weeks of double-blind escitalopram or placebo. Generalized psychophysiological interaction analysis was conducted to examine the functional connectivity of the amygdala while patients viewed emotional pictures. Full-factorial analysis was used to investigate the treatment effect of escitalopram on amygdala connectivity. Correlation analyses were performed to explore whether pretreatment and early (week 2) treatment-related connectivity were associated with treatment response (improvement in anxiety) at week 8. Compared to placebo, escitalopram enhanced emotional processing speed and enhanced negative right amygdala-bilateral ventromedial prefrontal cortex (vmPFC) and positive left amygdala-right angular gyrus connectivity during emotion processing. Baseline amygdala-vmPFC connectivity and escitalopram-induced increased amygdala-angular gyrus connectivity at week 2 predicted the magnitude of subsequent improvement in anxiety symptoms. These findings suggest that amygdala connectivity to hubs of the default mode network represents a target of acute SSRI treatment. Furthermore, pretreatment and early-treatment amygdala connectivity could serve as biomarkers of SSRI treatment response in adolescents with GAD. The trial registration for the study is ClinicalTrials.gov Identifier: NCT02818751.

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Steady advances in neuroscience have shaped understanding of brain and mind, in ways that challenge spiritual belief and can amplify misconceptions about biological determinism. The inability to reconcile spirituality and science risks faith being construed as “out of touch” with reality, and in worst‐case scenarios engendering clinical‐level crises of hope. The latter typically involve three central issues: the free will problem, desperate perceptions about mortality, and the constraint of individual identity. Here, we synthesize contemporary scientific and philosophical understanding to propose a reconciliation of faith and science of particular relevance to preservation of hope. In this approach, we review the compatibility of natural causation and human freedom, parameterize “meaning” on the basis of specific opportunities for decision‐making within the timeframe of a lifetime, and articulate a model of self‐transcendence predicated on these principles and on observed characteristics of human love. This model resides within “common ground” for faith and science by avoiding unnecessary dichotomization of the material and the Divine.

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