Modulation of nicotinic acetylcholine receptors (nAChRs), specifically α4β2 subunit containing nAChRs, may be effective in the treatment of patients with major depressive disorder (MDD). Using [123I] 5-I-A-85380 single photon emission computed tomography (SPECT), we studied β2 subunit containing nAChR (β2*-nAChR) availability in patients with MDD. In order to understand the molecular basis of the change in receptor availability, we also studied β2*-nAChR binding in postmortem samples of human brains of MDD subjects.
23 medication-free, early-onset, non-smoking subjects with familial MDD (8 acutely depressed (aMDD), 15 euthymic, recovered MDD subjects (rMDD)), and 23 age- and gender-matched, non-smoking controls had one [123I] 5-I-A-85380 SPECT scan and a magnetic resonance imaging (MRI) scan. β2*-nAChR availability was quantified as VT/fP. β2*-nAChR binding was analyzed in postmortem samples of the prefrontal cortex in 14 subjects with MDD and age-matched controls with [125I] 5-I-A-85380.
β2*-nAChR availability in aMDD and rMDD subjects was significantly lower across all brain regions than in respective controls and lower in aMDD subjects than in rMDD subjects. MDD patients showed significant correlations between β2*-nAChR availability and lifetime number of depressive episodes, trauma and anxiety scores. There were no differences in β2*-nAChR number between groups in the human postmortem study.
β2*-nAChR availability is decreased in patients with MDD. The difference between β2*-nAChR availability in vivo and in postmortem 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 increased endogenous acetylcholine.