Current perspectives of the roles of the central norepinephrine system in anxiety and depression

Andrew W. Goddard, Susan G. Ball, James Martinez, Michael J. Robinson, Charles R. Yang, James M. Russell, Anantha Shekhar

Research output: Contribution to journalReview article

142 Scopus citations


Norepinephrine (NE) is a major monoamine neurotransmitter that has widespread effects across multiple brain areas to regulate arousal and stress responses. The underlying function of the NE cortical system is to balance vigilance/scanning behavior with focused attention on novel environmental stimuli and the state of arousal. The central NE system is involved intrinsically with the stress response system, and dysregulation within the NE system has been implicated in the pathogenesis of anxiety and depressive disorders. Central NE activity paradoxically has either anxiogenic or anxiolytic effects, depending on whether the time course of the stress is acute or chronic, whether the stress is predictable or unpredictable, and which underlying brain regions are affected. Under conditions of chronic stress, NE system activity dysregulation of the hypothalamic-pituitary-adrenal system may turn a homeostatic stress response into a pathological stress response. Data suggest that the NE interplay with the serotonin system may exert neurobiological normalization of the pathophysiological state of anxious depression. Accordingly, pharmacological interventions targeting the NE system can result in anxiolytic, rather than anxiogenic, outcomes when used to treat patients with anxiety and depression.

Original languageEnglish (US)
Pages (from-to)339-350
Number of pages12
JournalDepression and anxiety
Issue number4
StatePublished - Apr 1 2010


  • Anxious
  • Neurobiology
  • Norepinephrine transporter
  • Pharmacotherapy
  • Stress

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

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