Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder

Aybala Saricicek, Irina Esterlis, Kathleen H. Maloney, Yann S. Mineur, Barbara M. Ruf, Anjana Muralidharan, Jason Chen, Kelly P. Cosgrove, Rebecca Kerestes, Subroto Ghose, Carol A. Tamminga, Brian Pittman, Frederic Bois, Gilles Tamagnan, John Seibyl, Marina R. Picciotto, Julie K. Staley, Zubin Bhagwagar

Research output: Contribution to journalArticle

63 Citations (Scopus)

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&z.ast;-nAChRs) in depressed patients. To understand its molecular basis, the authors also studied β2&z.ast;-nAChR binding in postmortem brain samples from depressed subjects. Method: 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&z.ast;-nAChRs was quantified as VT/fP. Postmortem analysis of β2&z.ast;-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&z.ast;-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&z.ast;-nAChR availability was significantly correlated with lifetime number of depressive episodes, trauma score, and anxiety score. There were no differences in β2&z.ast;-nAChR number between groups in the postmortem study. Conclusions: Depressed patients have lower β2&z.ast;-nAChR availability than do healthy subjects. The difference between β2&z.ast;-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 greater endogenous acetylcholine.

Original languageEnglish (US)
Pages (from-to)851-859
Number of pages9
JournalAmerican Journal of Psychiatry
Volume169
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

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Major Depressive Disorder
Nicotinic Receptors
Single-Photon Emission-Computed Tomography
Ligands
Dopamine Receptors
Brain
Prefrontal Cortex
Acetylcholine
Healthy Volunteers
Anxiety
Magnetic Resonance Imaging
Depression
Wounds and Injuries
5-iodo-3-(2-azetidinylmethoxy)pyridine

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Saricicek, A., Esterlis, I., Maloney, K. H., Mineur, Y. S., Ruf, B. M., Muralidharan, A., ... Bhagwagar, Z. (2012). Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder. American Journal of Psychiatry, 169(8), 851-859. https://doi.org/10.1176/appi.ajp.2012.11101546

Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder. / Saricicek, Aybala; Esterlis, Irina; Maloney, Kathleen H.; Mineur, Yann S.; Ruf, Barbara M.; Muralidharan, Anjana; Chen, Jason; Cosgrove, Kelly P.; Kerestes, Rebecca; Ghose, Subroto; Tamminga, Carol A.; Pittman, Brian; Bois, Frederic; Tamagnan, Gilles; Seibyl, John; Picciotto, Marina R.; Staley, Julie K.; Bhagwagar, Zubin.

In: American Journal of Psychiatry, Vol. 169, No. 8, 01.08.2012, p. 851-859.

Research output: Contribution to journalArticle

Saricicek, A, Esterlis, I, Maloney, KH, Mineur, YS, Ruf, BM, Muralidharan, A, Chen, J, Cosgrove, KP, Kerestes, R, Ghose, S, Tamminga, CA, Pittman, B, Bois, F, Tamagnan, G, Seibyl, J, Picciotto, MR, Staley, JK & Bhagwagar, Z 2012, 'Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder', American Journal of Psychiatry, vol. 169, no. 8, pp. 851-859. https://doi.org/10.1176/appi.ajp.2012.11101546
Saricicek, Aybala ; Esterlis, Irina ; Maloney, Kathleen H. ; Mineur, Yann S. ; Ruf, Barbara M. ; Muralidharan, Anjana ; Chen, Jason ; Cosgrove, Kelly P. ; Kerestes, Rebecca ; Ghose, Subroto ; Tamminga, Carol A. ; Pittman, Brian ; Bois, Frederic ; Tamagnan, Gilles ; Seibyl, John ; Picciotto, Marina R. ; Staley, Julie K. ; Bhagwagar, Zubin. / Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder. In: American Journal of Psychiatry. 2012 ; Vol. 169, No. 8. pp. 851-859.
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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&z.ast;-nAChRs) in depressed patients. To understand its molecular basis, the authors also studied β2&z.ast;-nAChR binding in postmortem brain samples from depressed subjects. Method: 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&z.ast;-nAChRs was quantified as VT/fP. Postmortem analysis of β2&z.ast;-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&z.ast;-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&z.ast;-nAChR availability was significantly correlated with lifetime number of depressive episodes, trauma score, and anxiety score. There were no differences in β2&z.ast;-nAChR number between groups in the postmortem study. Conclusions: Depressed patients have lower β2&z.ast;-nAChR availability than do healthy subjects. The difference between β2&z.ast;-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 greater endogenous acetylcholine.",
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AU - Esterlis, Irina

AU - Maloney, Kathleen H.

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AU - Ruf, Barbara M.

AU - Muralidharan, Anjana

AU - Chen, Jason

AU - Cosgrove, Kelly P.

AU - Kerestes, Rebecca

AU - Ghose, Subroto

AU - Tamminga, Carol A.

AU - Pittman, Brian

AU - Bois, Frederic

AU - Tamagnan, Gilles

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N2 - 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&z.ast;-nAChRs) in depressed patients. To understand its molecular basis, the authors also studied β2&z.ast;-nAChR binding in postmortem brain samples from depressed subjects. Method: 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&z.ast;-nAChRs was quantified as VT/fP. Postmortem analysis of β2&z.ast;-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&z.ast;-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&z.ast;-nAChR availability was significantly correlated with lifetime number of depressive episodes, trauma score, and anxiety score. There were no differences in β2&z.ast;-nAChR number between groups in the postmortem study. Conclusions: Depressed patients have lower β2&z.ast;-nAChR availability than do healthy subjects. The difference between β2&z.ast;-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 greater endogenous acetylcholine.

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