RT Journal
A1 Cannon DM, Carson RE, Nugent AC, et al
T1 REduced muscarinic type 2 receptor binding in subjects with bipolar disorder
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2006
FD July 1
VO 63
IS 7
SP 741
OP 747
DO 10.1001/archpsyc.63.7.741
UL http://dx.doi.org/10.1001/archpsyc.63.7.741
AB Context 
    A variety of indirect evidence has implicated the central muscarinic-cholinergic system, and more specifically the type 2 muscarinic (M2) receptor, in the pathogenesis of depressive symptoms arising in major depressive disorder and bipolar disorder.Objective 
    To assess the binding potential of muscarinic2 receptors in vivo during depression in subjects with major depressive disorder or bipolar disorder.Design 
    The M2 receptor binding was compared between unmedicated subjects with major depressive disorder or bipolar disorder during depression vs healthy controls, using positron emission tomography and [18F]FP-TZTP (fluorodopa F 18 [3-(3-[3-fluoroproply]thio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine), a selective M2 receptor radioligand.Setting 
    Outpatients at the National Institutes of Health.Participants 
    Unmedicated subjects with current depression meeting DSM-IV criteria for either major depressive disorder (n = 17) or bipolar disorder (n = 16) and 23 healthy control subjects.Main Outcome Measures 
    The primary outcome parameter was [18F]FP-TZTP distribution volume, which is proportional to the product of receptor density and affinity and, in the case of [18F]FP-TZTP, is known to be sensitive to endogenous acetylcholine concentrations. The relationship between illness severity, as rated using the Montgomery-Asberg Depression and Hamilton Anxiety Rating scales, and distribution volume also was assessed.Results 
    The mean anterior cingulate cortex distribution volume differed across groups (F55 = 3.4; P = .04), and this difference was accounted for by significantly lower binding in bipolar disorder compared with both major depressive disorder and control groups.Conclusions 
    The mean M2 receptor binding in subjects with bipolar disorder was reduced relative to both healthy controls and subjects with major depressive disorder, to an extent that correlated with depressive symptoms. The reduction in the bipolar disorder group could be accounted for either by a reduction in M2 receptor density or affinity or an elevation in endogenous acetylcholine levels. To our knowledge, these data provide the first direct evidence that altered M2 receptor function contributes to mood dysregulation in bipolar disorder.