Brain functional connectivity during induced sadness in patients with obsessive–compulsive disorder

Brain functional connectivity during induced sadness in patients with obsessive–compulsive disorder


J Psychiatry Neurosci 2012;37(4):231-40

Leonardo F. Fontenelle, MD, PhD; Ben J. Harrison, PhD; Jesus Pujol, MD; Christopher G. Davey, MD, PhD; Alex Fornito, PhD; Emre Bora, MD; Christos Pantelis, MD; Murat Yücel, PhD, MAPSD

Fontenelle, Harrison, Davey, Fornito, Bora, Pantelis, Yücel — Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Australia; Fontenelle — Anxiety and Depression Research Program, Institute of Psychiatry, Universidade Federal do Rio de Janeiro, and D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Pujol — Institut d’Alta Tecnologia-PRBB, CRC Mar, Hospital del Mar, Barcelona, Spain; Davey — Orgyen Youth Health Research Centre, University of Melbourne, Australia


Background: Obsessive–compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation.

Methods: Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness.

Results: We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus.

Limitations: Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis.

Conclusion: The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized “OCD circuit,” which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.

Submitted July 16, 2011; Revised Oct. 24, Dec. 13, 2011; Accepted Dec. 20, 2011.

Competing interests: None declared for J. Pujol and E. Bora. L.F. Fontenelle declares having received grant funding from the Department of Education, Employment, and Workplace Relations, government of Australia (Endeavour Research Fellowship Award #1415_2010) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (Bolsa de Produtividade em Pesquisa #303846/ 2008- 9). B.J. Harrison is supported by a National Health and Medical Research Council of Australia (NHMRC) Clinical Career Development Award (ID 628509). C.G. Davey is supported by an NHMRC Training (postdoctoral) Fellowship (ID 628922). A. Fornito is supported by an NHMRC CJ Martin Fellowship (ID 454797). C. Pantelis is supported by an NHMRC Senior Principal Research Fellowship (ID 628386) and NHMRC program grants (ID 350241, 566529). M. Yücel is supported by an NHMRC Fellowship Award (ID 1001973). This research was supported by an NHMRC project grant (ID 236175).

Contributors: B.J. Harrison and M. Yücel designed the study. B.J.Harrison, A. Fornito and M. Yücel acquired the data. L.F. Fontenelle, B.J. Harrison and A. Fornito wrote the article. All authors analyzed the data, reviewed the article and approved its publication.

DOI: 10.1503/jpn.110074

Correspondence to: L.F. Fontenelle, Rua Visconde de Pirajá 547, 719, Ipanema, Rio de Janeiro-RJ, Brazil, CEP: 22410-003;