Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls


J Psychiatry Neurosci 2015;40(2):134-142

Jiri Horacek, MD, PhD; Pavol Mikolas, MD; Jaroslav Tintera, CSc; Tomas Novak, MD, PhD; Tomas Palenicek, MD, PhD; Martin Brunovsky, MD, PhD; Cyril Höschl MD, DrSc; Martin Alda, MD


Background: Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls.

Methods: Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response.

Results: We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls (F1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus (p ≤ 0.05, family-wise error–corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls.

Limitations: Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity.

Conclusion: Our results support the role of the amygdala–vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD.

Submitted Feb. 9, 2014; Revised Aug. 1, 2014; Accepted Sept. 16, 2014; Early-released Dec. 16. 2014.

Acknowledgments: J. Horacek is supported by a 2009 NARSAD Independent Investigator Award and grants from the Ministry of Health of the Czech Republic (DRO PCP, 00023752 and IGA NT12024). The authors thank H. Fridrichova, N. Gornerova, M. Holec and I. Ibrahim for technical assistance and participant recruitment, and J. Garnham and C. Hampson for language editing.

Affiliations: Prague Psychiatric Centre, Prague, Czech Republic (Horacek, Mikolas, Novak, Palenicek, Brunovsky, Höschl); Third Faculty of Medicine, Charles University, Prague, Czech Republic (Horacek, Novak, Palenicek, Brunovsky, Höschl, Alda); Department of Psychiatry, Dalhousie University, Halifax, Canada (Horacek, Alda); Institute for Clinical and Experimental Medicine, Prague, Czech Republic (Tintera).

Competing interests: J. Horacek has received a speaking honorarium from Janssen Cilag, Zentiva group, Eli Lilly, Lundbeck, Novartis, Pfizer and MEDA Pharma. He has also received grant support from NARSAD and the Ministry of Health, Czech Republic. C. Höschl has served as a study coordinator with Servier, a faculty member of the Lundbeck International Neuroscience Foundation and as a speaker for Eli Lilly, Janssen Cilag and Krka. M. Brunovsky has served as an adviser and speaker for Hoffmann-La Roche, Krka, MEDA Pharma, Novartis and Zentiva group. M. Alda has received grants from Canadian Institutes of Health Research, Genome Quebec, Nova Scotia Health Research Foundation, Stanley Foundation, NARSAD, and Killam Trust. No other competing interests declared.

Contributors: J. Horacek and M. Alda designed the study. J. Horacek, J. Tintera, T. Palenicek and M. Brunovsky acquired the data, which J. Horacek, M. Alda, C. Höschl, T. Novak and P. Mikolas analyzed. J. Horacek and M. Alda wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140044

Correspondence to: J. Horacek, Prague Psychiatric Centre, Ustavni 91, 181 03 Prague 8, Czech Republic EU;