title: Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder.
abstract: BACKGROUND
  Modulation of nicotinic acetylcholine receptors (nAChRs), specifically those containing the β2 subunit, may be effective in treating patients with major depressive disorder. Using [123I]5-I-A-85380 single photon emission computed tomography (SPECT), the authors studied the availability of β2-subunit-containing nAChRs (β2*-nAChRs) in depressed patients. To understand its molecular basis, the authors also studied β2*-nAChR binding in postmortem brain samples from depressed subjects.
  
  
  METHODS
  The participants were 23 medication-free, nonsmoking subjects with familial, early-onset depression (eight acutely ill and 15 recovered) and 23 age- and gender-matched nonsmoking comparison subjects. Each received one [123I]5-I-A-85380 SPECT scan and an MRI scan. The availability of β2*-nAChRs was quantified as VT/fP. Postmortem analysis of β2*-nAChR binding was conducted with [123I]5-I-A-85380 on prefrontal cortex samples from 14 depressed subjects and 14 age-matched comparison subjects.
  
  
  RESULTS
  The β2*-nAChR availability in both the acutely ill and recovered depressed subjects was significantly lower across all brain regions than in the respective comparison subjects, and it was lower in the acutely ill subjects than in those who were recovered. In the depressed patients, β2*-nAChR availability was significantly correlated with lifetime number of depressive episodes, trauma score, and anxiety score. There were no differences in β2*-nAChR number between groups in the postmortem study.
  
  
  CONCLUSIONS
  Depressed patients have lower β2*-nAChR availability than do healthy subjects. The difference between β2*-nAChR availability in vivo and in post-mortem samples may be analogous to data with dopaminergic PET ligands and dopamine receptor availability; lower receptor availability for the SPECT ligand could be caused by greater endogenous acetylcholine.
authors: Department of Psychiatry, Yale University, New Haven, CT, USA. aybala.saricicek@yahoo.com
authors: Aybala
authors: A
authors: Saricicek
authors: Irina
authors: I
authors: Esterlis
authors: Kathleen H
authors: KH
authors: Maloney
authors: Yann S
authors: YS
authors: Mineur
authors: Barbara M
authors: BM
authors: Ruf
authors: Anjana
authors: A
authors: Muralidharan
authors: Jason I
authors: JI
authors: Chen
authors: Kelly P
authors: KP
authors: Cosgrove
authors: Rebecca
authors: R
authors: Kerestes
authors: Subroto
authors: S
authors: Ghose
authors: Carol A
authors: CA
authors: Tamminga
authors: Brian
authors: B
authors: Pittman
authors: Frederic
authors: F
authors: Bois
authors: Gilles
authors: G
authors: Tamagnan
authors: John
authors: J
authors: Seibyl
authors: Marina R
authors: MR
authors: Picciotto
authors: Julie K
authors: JK
authors: Staley
authors: Zubin
authors: Z
authors: Bhagwagar
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D011569:Psychiatric Status Rating Scales; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D011978:Receptors, Nicotinic