Serotonergic systems, anxiety, and affective disorder: Focus on the dorsomedial part of the dorsal raphe nucleus

Christopher A. Lowry, Matthew W. Hale, Andrew K. Evans, Jasper Heerkens, Daniel R. Staub, Paul J. Gasser, Anantha Shekhar

Research output: Chapter in Book/Report/Conference proceedingConference contribution

187 Scopus citations


Depressed suicide patients have elevated expression of neuronal tryptophan hydroxylase 2 (TPH2) mRNA and protein in midbrain serotonergic neurons, as well as increases in brain serotonin turnover. The mechanisms underlying these changes are uncertain, but increased TPH2 expression and serotonin turnover could result from genetic influences, adverse early life experiences, or acute stressful life events, all of which can alter serotonergic neurotransmission and have been implicated in determining vulnerability to major depression. Emerging evidence suggests that there are several different stress-related subsets of serotonergic neurons, each with a unique role in the integrated stress response. Here we review our current understanding of how genetic and environmental factors may influence TPH2 mRNA expression and serotonergic neurotransmission, focusing in particular on the dorsomedial part of the dorsal raphe nucleus. This subdivision of the dorsal raphe nucleus is selectively innervated by key forebrain structures implicated in regulation of anxiety states, it gives rise to projections to a distributed neural system mediating anxiety states, and serotonergic neurons within this subdivision are selectively activated by a number of stress- and anxiety-related stimuli. A better understanding of the anatomical and functional properties of specific stress- or anxiety-related serotonergic systems should aid our understanding of the neural mechanisms underlying the etiology of anxiety and affective disorders.

Original languageEnglish (US)
Title of host publicationStress, Neurotransmitters, and Hormones Neuroendocrine and Genetic Mechanisms
PublisherBlackwell Publishing Inc.
Number of pages9
ISBN (Print)9781573316927
StatePublished - Dec 2008

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Anxiety
  • Dorsal raphe
  • Serotonin
  • Serotonin transporter
  • Stress
  • TPH2
  • Tryptophan hydroxylase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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