OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

Christopher Pittenger; Thomas G. Adams; Jean Dominique Gallezot; Michael J. Crowley; Nabeel Nabulsi; Ropchan James; Hong Gao; Stephen A. Kichuk; Ryan Simpson; Eileen Billingslea; Jonas Hannestad; Michael Bloch; Linda Mayes; Zubin Bhagwagar; Richard E. Carson

doi:10.1016/j.jad.2016.02.021

OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

Christopher Pittenger, Thomas G. Adams, Jean Dominique Gallezot, Michael J. Crowley, Nabeel Nabulsi, Ropchan James, Hong Gao, Stephen A. Kichuk, Ryan Simpson, Eileen Billingslea, Jonas Hannestad, Michael Bloch, Linda Mayes, Zubin Bhagwagar, Richard E. Carson

Psychology

Research output: Contribution to journal › Article › peer-review

22 Citations (SciVal)

Abstract

Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT_1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT_1B receptor availability using ¹¹C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n=12) and matched healthy controls (HC; n=12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT_1B receptor availability (¹¹C-P943 BP_ND); however, the relationship between PPI and ¹¹C-P943 BP_ND differed dramatically and significantly between groups. 5-HT_1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT_1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT_1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD.

Original language	English
Pages (from-to)	87-96
Number of pages	10
Journal	Journal of Affective Disorders
Volume	196
DOIs	https://doi.org/10.1016/j.jad.2016.02.021
State	Published - May 15 2016

Bibliographical note

Funding Information:
The authors gratefully acknowledge the staff of the Yale PET Center, and Brian Pittman, MS, for biostatistical support. This work was supported by NIH grants R21MH090555 (CP), K08MH081190 (CP), T32MH062994 (TA; M. Bell, PI), and CTSA Grant no. UL1TR000142 from the National Center for Advancing Translational Science (NCATS). Its content is solely the responsibility of the authors and does not necessarily reflect the official view of NIH. Additional support came from the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center. The authors have no real or apparent conflict of interest of relevance to this work.

Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.

ASJC Scopus subject areas

Clinical Psychology
Psychiatry and Mental health

UN SDGs

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10.1016/j.jad.2016.02.021

Cite this

Pittenger, C., Adams, T. G., Gallezot, J. D., Crowley, M. J., Nabulsi, N., James, R., Gao, H., Kichuk, S. A., Simpson, R., Billingslea, E., Hannestad, J., Bloch, M., Mayes, L., Bhagwagar, Z., & Carson, R. E. (2016). OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding. Journal of Affective Disorders, 196, 87-96. https://doi.org/10.1016/j.jad.2016.02.021

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title = "OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding",

abstract = "Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using 11C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n=12) and matched healthy controls (HC; n=12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability (11C-P943 BPND); however, the relationship between PPI and 11C-P943 BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD.",

author = "Christopher Pittenger and Adams, {Thomas G.} and Gallezot, {Jean Dominique} and Crowley, {Michael J.} and Nabeel Nabulsi and Ropchan James and Hong Gao and Kichuk, {Stephen A.} and Ryan Simpson and Eileen Billingslea and Jonas Hannestad and Michael Bloch and Linda Mayes and Zubin Bhagwagar and Carson, {Richard E.}",

note = "Funding Information: The authors gratefully acknowledge the staff of the Yale PET Center, and Brian Pittman, MS, for biostatistical support. This work was supported by NIH grants R21MH090555 (CP), K08MH081190 (CP), T32MH062994 (TA; M. Bell, PI), and CTSA Grant no. UL1TR000142 from the National Center for Advancing Translational Science (NCATS). Its content is solely the responsibility of the authors and does not necessarily reflect the official view of NIH. Additional support came from the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center. The authors have no real or apparent conflict of interest of relevance to this work. Publisher Copyright: {\textcopyright} 2016 Elsevier B.V. All rights reserved.",

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Pittenger, C, Adams, TG, Gallezot, JD, Crowley, MJ, Nabulsi, N, James, R, Gao, H, Kichuk, SA, Simpson, R, Billingslea, E, Hannestad, J, Bloch, M, Mayes, L, Bhagwagar, Z & Carson, RE 2016, 'OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding', Journal of Affective Disorders, vol. 196, pp. 87-96. https://doi.org/10.1016/j.jad.2016.02.021

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T1 - OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

AU - Pittenger, Christopher

AU - Adams, Thomas G.

AU - Gallezot, Jean Dominique

AU - Crowley, Michael J.

AU - Nabulsi, Nabeel

AU - James, Ropchan

AU - Gao, Hong

AU - Kichuk, Stephen A.

AU - Simpson, Ryan

AU - Billingslea, Eileen

AU - Hannestad, Jonas

AU - Bloch, Michael

AU - Mayes, Linda

AU - Bhagwagar, Zubin

AU - Carson, Richard E.

N1 - Funding Information: The authors gratefully acknowledge the staff of the Yale PET Center, and Brian Pittman, MS, for biostatistical support. This work was supported by NIH grants R21MH090555 (CP), K08MH081190 (CP), T32MH062994 (TA; M. Bell, PI), and CTSA Grant no. UL1TR000142 from the National Center for Advancing Translational Science (NCATS). Its content is solely the responsibility of the authors and does not necessarily reflect the official view of NIH. Additional support came from the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center. The authors have no real or apparent conflict of interest of relevance to this work. Publisher Copyright: © 2016 Elsevier B.V. All rights reserved.

PY - 2016/5/15

Y1 - 2016/5/15

N2 - Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using 11C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n=12) and matched healthy controls (HC; n=12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability (11C-P943 BPND); however, the relationship between PPI and 11C-P943 BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD.

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OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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