title: Changes in the cholinergic system between bipolar depression and euthymia as measured with [123I]5IA single photon emission computed tomography.
abstract: BACKGROUND
  The cholinergic system is substantially altered in individuals with major depression and is partially restored when depression remits. We quantified the availability of β2-subunit-containing nicotinic acetylcholine receptors (β2*-nAChR) in subjects with bipolar disorder.
  
  
  METHODS
  Twenty-five subjects with bipolar disorder (15 depressed, 10 euthymic) and 25 sex- and age-matched control subjects had a [(123)I]5IA-85380 single photon emission computed tomography scan to quantify β2*-nAChR VT/fP (total volume of distribution, corrected for individual differences in metabolism and protein binding of the radiotracer). Average VT/fP was compared between groups and correlated with clinical characteristics. Postmortem analysis of β2*-nAChRs was conducted using equilibrium binding with [(125)I]5IA in subjects with bipolar disorder and matched control subjects.
  
  
  RESULTS
  We showed significantly lower β2*-nAChR availability (20%-38%) in subjects with bipolar depression compared with euthymic and control subjects across all brain regions assessed (frontal, parietal, temporal, and anterior cingulate cortex, hippocampus, amygdala, thalamus, striatum). The postmortem binding study in which endogenous acetylcholine was washed out did not show a statistically significant difference in β2*-nAChR number in temporal cortex of the bipolar depressed and control groups (15% difference; p = .2).
  
  
  CONCLUSIONS
  We show that the alteration in the cholinergic system observed during a depressive episode appears to resolve during euthymia. We suggest that lower VT/fP observed in vivo may be due to a combination of higher endogenous acetylcholine levels during depression, which could compete with radiotracer binding to the receptor in vivo, and lower receptor number in bipolar depression. Identification of differences in cholinergic signaling in subjects with bipolar depression may improve our understanding of its etiology and reveal new treatment targets.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; UCB Pharma SA, Braine-l'Alleud, Belgium.
authors.forename: Jonas O
authors.initials: JO
authors.lastname: Hannestad
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.forename: Nicole F
authors.initials: NF
authors.lastname: DellaGioia
authors.forename: Evgenia
authors.initials: E
authors.lastname: Perkins
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Zubin
authors.initials: Z
authors.lastname: Bhagwagar
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Tristan D
authors.initials: TD
authors.lastname: McClure-Begley
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
mesh_terms: D000328:Adult; D001384:Azetidines / Q000008:administration & dosage; D001714:Bipolar Disorder / Q000378:metabolism*; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008297:Male; D011725:Pyridines / Q000008:administration & dosage; D011978:Receptors, Nicotinic / Q000032:analysis*; D012907:Smoking; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001384:Azetidines; D011725:Pyridines; D011978:Receptors, Nicotinic; C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine
keywords: Acetylcholine; SPECT; bipolar disorder; depression; tobacco smoking; β(2)*-nAChR