title: Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism.
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.
authors.affiliation: Karolinska Institutet, Neurotec Department, Division of Psychiatry, Huddinge University Hospital, M57, SE-141 86, Stockholm, Sweden. markus.heilig@neurotec.ki.se
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.forename: Olof
authors.initials: O
authors.lastname: Zachrisson
authors.forename: Annika
authors.initials: A
authors.lastname: Thorsell
authors.forename: Anna
authors.initials: A
authors.lastname: Ehnvall
authors.forename: Salim
authors.initials: S
authors.lastname: Mottagui-Tabar
authors.forename: Magnus
authors.initials: M
authors.lastname: Sjögren
authors.forename: Marie
authors.initials: M
authors.lastname: Asberg
authors.forename: Rolf
authors.initials: R
authors.lastname: Ekman
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.forename: Hans
authors.initials: H
authors.lastname: Agren
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004351:Drug Resistance; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011498:Protein Precursors / Q000134:cerebrospinal fluid* / Q000235:genetics*; D012008:Recurrence
chemical_list: D015415:Biomarkers; D009478:Neuropeptide Y; D011498:Protein Precursors; C042084:preproneuropeptide Y