Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders

Kerry J. Ressler, Charles B. Nemeroff

Research output: Contribution to journalReview articlepeer-review

736 Scopus citations


There is abundant evidence for abnormalities of the norepinephrine (NE) and serotonin (5HT) neurotransmitter systems in depression and anxiety disorders. The majority of evidence supports underactivation of serotonergic function and complex dysregulation of noradrenergic function, most consistent with overactivation of this system. Treatment for these disorders requires perturbation of these systems. Reproducible increases in serotonergic function and decreases in noradrenergic function accompany treatment with antidepressants, and these alterations may be necessary for antidepressant efficacy. Dys-regulation of these systems clearly mediates many symptoms of depression and anxiety. The underlying causes of these disorders, however, are less likely to be found within the NE and 5HT systems, per se. Rather their dysfunction is likely due to their role in modulating, and being modulated by, other neurobiologic systems that together mediate the symptoms of affective illness. Clarification of noradrenergic and serotonergic modulation of various brain regions may yield a greater understanding of specific symptomatology, as well as the underlying circuitry involved in euthymic and abnormal mood and anxiety states. Disrupted cortical regulation may mediate impaired concentration and memory, together with uncontrollable worry. Hypothalamic abnormalities likely contribute to altered appetite, libido, and autonomic symptoms. Thalamic and brainstem dysregulation contributes to altered sleep and arousal states. Finally, abnormal modulation of cortical-hippocampal-amygdala pathways may contribute to chronically hypersensitive stress and fear responses, possibly mediating features of anxiety, anhedonia, aggression, and affective dyscontrol. The continued appreciation of the neural circuitry mediating affective states and their modulation by neurotransmitter systems should further the understanding of the pathophysiology of affective and anxiety disorders. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)2-19
Number of pages18
JournalDepression and anxiety
Issue numberSUPPL. 1
StatePublished - Nov 20 2000
Externally publishedYes


  • Anxiety
  • Depression
  • Norepinephrine
  • Pathophysiology
  • Serotonin

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Psychology(all)
  • Clinical Psychology


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