Neural activation of anxiety and depression in children and young people: A systematic meta-analysis of fMRI studies

Psychiatry Res Neuroimaging. 2021 May 30:311:111272. doi: 10.1016/j.pscychresns.2021.111272. Epub 2021 Mar 10.


Functional magnetic resonance imaging (fMRI) studies consistently demonstrate altered neural activation in youth experiencing anxiety and depression in a way that is distinct from adult-onset disorders. However, there is a paucity of research systematically reviewing this, and no meta-analyses have been conducted using Activation Likelihood Estimation (ALE). The present study conducted a systematic literature search to identify fMRI studies in youth (age 4-18) with depression or anxiety disorders. 48 studies with over 2000 participants were identified that met the inclusion criteria. Significant foci were extracted. Five ALE meta-analyses were conducted: a) activation for both anxiety disorders and depression; b) activation for anxiety disorders only; c) activation for depression only; d) deactivation for both anxiety disorders and depression; e) deactivation for depression. Results indicated significant clusters of increased activation in the bilateral amygdala for youth with internalising disorders, and specifically for those with anxiety disorders. Significant increased activation extended into the dorsal anterior cingulate, entorhinal cortex, the putamen, and the medial and lateral globus pallidus in youth with anxiety disorders. These findings help to detail the nature of anxiety being an amygdala hyperactivity disorder, whilst also defining the distinction between neural activation patterns in anxiety and depression.

Keywords: Activation likelihood estimation; Amygdala; Functional magnetic resonance imaging; Internalising disorders; Mood disorders; Youth.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Anxiety / diagnostic imaging
  • Anxiety Disorders / diagnostic imaging
  • Brain / diagnostic imaging
  • Child
  • Child, Preschool
  • Depression* / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging*