Neural structures, functioning and connectivity in Generalized Anxiety Disorder and interaction with neuroendocrine systems: a systematic review

J Affect Disord. 2014 Apr;158:114-26. doi: 10.1016/j.jad.2014.01.022. Epub 2014 Feb 12.


Background: Research on the neurobiological basis of Generalized Anxiety Disorder (GAD) has considerably expanded in recent years. However, many studies investigated different domains and used different methods and paradigms. Therefore, this review aims to integrate the findings to date and to identify the core correlates of neurobiological underpinnings of GAD discovered so far.

Methods: We conducted a systematic review of original papers investigating neural correlates, connectivity, or structural changes as well as reporting changes in the serotonergic system, noradrenergic system and cortisol levels in DSM-IV-defined GAD samples until December 2013.

Results: Studies have identified abnormal amygdala and prefrontal cortex activation in patients and decreased functional connectivity between these areas. Furthermore, studies showed increased gray matter volume and decreased structural connectivity between these structures. Neuroendocrine findings are less consistent, but increased reactivity of the noradrenergic system and perpetuations in the cortisol secretion have been reported.

Limitations: Only studies on DSM-IV defined Generalized Anxiety Disorder which employed a group comparison were included.

Conclusions: Current research suggests a distinct set of neurobiological alterations in Generalized Anxiety Disorder. However, future research on the interaction between these structures and systems and on the specificity of these findings in relation to other mental disorders is urgently needed.

Keywords: Anxiety disorder; Connectivity; Endocrinology; Generalized Anxiety Disorder; Neuroimaging; fMRI.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Amygdala / physiopathology
  • Anxiety Disorders / physiopathology*
  • Case-Control Studies
  • Diagnostic and Statistical Manual of Mental Disorders
  • Gray Matter / pathology
  • Gray Matter / physiopathology
  • Humans
  • Neurosecretory Systems / physiopathology*
  • Organ Size
  • Prefrontal Cortex / physiopathology