Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: Preliminary evidence for association with preproNPY gene polymorphism

Markus Heilig, Olof Zachrisson, Annika Thorsell, Anna Ehnvall, Salim Mottagui-Tabar, Magnus Sjögren, Marie Åsberg, Rolf Ekman, Claes Wahlestedt, Hans Ågren

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Extensive animal studies suggest neuropeptide Y (NPY) to be involved in coping with a wide range of stressors, and that impaired central NPY signalling could be involved in the pathophysiology of anxiety and depression. Human studies of central NPY levels in depression have, however, been inconclusive. Here, we examined levels of NPY-like immunoreactivity (NPY-LI) in the cerebrospinal fluid (CSF) of medication-free subjects with treatment refractory unipolar depression. Patients were admitted to a research inpatient unit, examined under standardized conditions, and compared with a sample of volunteers in whom psychiatric morbidity was excluded. A robust suppression of NPY levels in patient CSF was found, while other putative CSF markers (monoamine metabolites, somatostatin) did not differ between the groups. We then explored whether this finding might be related to a recently described T1128C coding polymorphism which results in a Leu7-> Pro7 substitution of the signal peptide, and a previously not described T -399C polymorphism in the promoter region of the preproNPY gene. Preliminary evidence was found for an association of both markers with a diagnosis of depression, indicating the possibility of an underlying haplotype influencing the vulnerability for developing depressive illness. Our present findings are in line with an extensive animal literature, and further support the notion that impaired NPY function could contribute to depressive illness.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalJournal of Psychiatric Research
Volume38
Issue number2
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

Keywords

  • Cerebrospinal fluid
  • Genetics
  • Immunoreactivity
  • Major depressive disorder
  • NPY
  • Polymorphism

ASJC Scopus subject areas

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

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