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Neural responses during down-regulation of negative emotion in patients with recently diagnosed bipolar disorder and their unaffected relatives

Published online by Cambridge University Press:  31 August 2021

Hanne Lie Kjærstad Open the ORCID record for Hanne Lie Kjærstad [Opens in a new window] ,
Julian Macoveanu Open the ORCID record for Julian Macoveanu [Opens in a new window] ,
Gitte Moos Knudsen Open the ORCID record for Gitte Moos Knudsen [Opens in a new window] ,
Sophia Frangou Open the ORCID record for Sophia Frangou [Opens in a new window] ,
K. Luan Phan ,
Maj Vinberg Open the ORCID record for Maj Vinberg [Opens in a new window] ,
Lars Vedel Kessing Open the ORCID record for Lars Vedel Kessing [Opens in a new window]  and
Kamilla Woznica Miskowiak Open the ORCID record for Kamilla Woznica Miskowiak [Opens in a new window]
Hanne Lie Kjærstad*
Affiliation:
Copenhagen Affective Disorder research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark
Julian Macoveanu
Affiliation:
Copenhagen Affective Disorder research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark
Gitte Moos Knudsen
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Denmark
Sophia Frangou
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
K. Luan Phan
Affiliation:
Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, USA
Maj Vinberg
Affiliation:
Copenhagen Affective Disorder research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark Psychiatric Research Unit, Psychiatric Centre North Zealand, Hillerød, Denmark
Lars Vedel Kessing
Affiliation:
Copenhagen Affective Disorder research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark
Kamilla Woznica Miskowiak
Affiliation:
Copenhagen Affective Disorder research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark Department of Psychology, University of Copenhagen, Copenhagen, Denmark
*
Author for correspondence: Hanne Lie Kjærstad, E-mail: hanne.lie.kjaerstad@regionh.dk
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Abstract

Background

Aberrant emotion regulation has been posited as a putative endophenotype of bipolar disorder (BD). We therefore aimed to compare the neural responses during voluntary down-regulation of negative emotions in a large functional magnetic resonance imaging study of BD, patients' unaffected first-degree relatives (URs), and healthy controls (HCs).

Methods

We compared neural activity and fronto-limbic functional connectivity during emotion regulation in response to aversive v. neutral pictures in patients recently diagnosed with BD (n = 78) in full/partial remission, their URs (n = 35), and HCs (n = 56).

Results

Patients showed hypo-activity in the left dorsomedial, dorsolateral, and ventrolateral prefrontal cortex (DMPFC and DLPFC) during emotion regulation while viewing aversive pictures compared to HCs, with URs displaying intermediate neural activity in these regions. There were no significant differences between patients with BD and HCs in functional connectivity from the amygdala during emotion regulation. However, exploratory analysis indicated that URs displayed more negative amygdala–DMPFC coupling compared with HCs and more negative amygdala-cingulate DLPFC coupling compared to patients with BD. At a behavioral level, patients and their URs were less able to dampen negative emotions in response aversive pictures.

Conclusions

The findings point to deficient recruitment of prefrontal resources and more negative fronto-amygdala coupling as neural markers of impaired emotion regulation in recently diagnosed remitted patients with BD and their URs, respectively.

Keywords

Emotion regulationbipolar disorderhigh-riskrelativesfMRIfunctional connectivitychildhood trauma
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 4 , March 2023 , pp. 1254 - 1265
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Aas, M., Henry, C., Andreassen, O. A., Bellivier, F., Melle, I., & Etain, B. (2016). The role of childhood trauma in bipolar disorders. International Journal of Bipolar Disorders, 4(1), 2. doi:10.1186/s40345-015-0042-0CrossRefGoogle ScholarPubMed
Aas, M., Henry, C., Bellivier, F., Lajnef, M., Gard, S., Kahn, J.-P., … Leboyer, M. (2017). Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders. Psychological Medicine, 47(5), 902–912.CrossRefGoogle ScholarPubMed
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®). Arlington, VA: Author.Google Scholar
Baldessarini, R. J., Tondo, L., Baethge, C. J., Lepri, B., & Bratti, I. M. (2007). Effects of treatment latency on response to maintenance treatment in manic-depressive disorders. Bipolar Disorders, 9(4), 386–393.CrossRefGoogle ScholarPubMed
Baldessarini, R. J., Tondo, L., Vázquez, G. H., Undurraga, J., Bolzani, L., Yildiz, A., … Lolich, M. (2012). Age at onset versus family history and clinical outcomes in 1665 international bipolar-I disorder patients. World Psychiatry, 11(1), 40–46.CrossRefGoogle Scholar
Banks, S. J., Eddy, K. T., Angstadt, M., Nathan, P. J., & Phan, K. L. (2007). Amygdala–frontal connectivity during emotion regulation. Social Cognitive and Affective Neuroscience, 2(4), 303–312.CrossRefGoogle ScholarPubMed
Blair, K., Smith, B., Mitchell, D., Morton, J., Vythilingam, M., Pessoa, L., … Drevets, W. (2007). Modulation of emotion by cognition and cognition by emotion. Neuroimage, 35(1), 430–440.CrossRefGoogle ScholarPubMed
Chen, C.-H., Suckling, J., Lennox, B. R., Ooi, C., & Bullmore, E. T. (2011). A quantitative meta-analysis of fMRI studies in bipolar disorder: Meta-analysis of fMRI studies in BD. Bipolar Disorders, 13(1), 1–15. doi:10.1111/j.1399-5618.2011.00893.xCrossRefGoogle Scholar
Coello, K., Munkholm, K., Nielsen, F., Vinberg, M., & Kessing, L. V. (2019). Hair cortisol in newly diagnosed bipolar disorder and unaffected first-degree relatives. Psychoneuroendocrinology, 99, 183–190.CrossRefGoogle ScholarPubMed
Corbalán, F., Beaulieu, S., & Armony, J. (2015). Emotion regulation in bipolar disorder type I: An fMRI study. Psychological Medicine, 45(12), 2521–2531.CrossRefGoogle ScholarPubMed
Daruy-Filho, L., Brietzke, E., Lafer, B., & Grassi-Oliveira, R. (2011). Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatrica Scandinavica, 124(6), 427–434.CrossRefGoogle ScholarPubMed
Delvecchio, G., Sugranyes, G., & Frangou, S. (2013). Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: A meta-analysis of functional imaging studies. Psychological Medicine, 43(3), 553–569.CrossRefGoogle ScholarPubMed
Desikan, R. S., Ségonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., … Hyman, B. T. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage, 31(3), 968–980.CrossRefGoogle ScholarPubMed
Dodd, A., Lockwood, E., Mansell, W., & Palmier-Claus, J. (2019). Emotion regulation strategies in bipolar disorder: A systematic and critical review. Journal of Affective Disorders, 246, 262–284.CrossRefGoogle ScholarPubMed
Fritz, K., Russell, A. M., Allwang, C., Kuiper, S., Lampe, L., & Malhi, G. S. (2017). Is a delay in the diagnosis of bipolar disorder inevitable? Bipolar Disorders, 19(5), 396–400.CrossRefGoogle ScholarPubMed
Goodwin, G. M., Martinez-Aran, A., Glahn, D. C., & Vieta, E. (2008). Cognitive impairment in bipolar disorder: Neurodevelopment or neurodegeneration? An ECNP expert meeting report. European Neuropsychopharmacology, 18(11), 787–793.CrossRefGoogle ScholarPubMed
Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. The American Journal of Psychiatry, 160, 636–645. doi:10.1176/appi.ajp.160.4.636CrossRefGoogle ScholarPubMed
Hamilton, M. (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6(4), 278–296. doi:10.1111/j.2044-8260.1967.tb00530.xCrossRefGoogle ScholarPubMed
Kanske, P., Schönfelder, S., Forneck, J., & Wessa, M. (2015). Impaired regulation of emotion: Neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives. Translational Psychiatry, 5(1), e497.CrossRefGoogle ScholarPubMed
Kessing, L. V., Munkholm, K., Faurholt-Jepsen, M., Miskowiak, K. W, Nielsen, L. B., Frikke-Schmidt, R., … Vinberg, M. (2017). The bipolar illness onset study – Research protocol for the BIO cohort study. BMJ Open, 7, e015462, 1–12.CrossRefGoogle ScholarPubMed
Ladouceur, C. D., Farchione, T., Diwadkar, V., Pruitt, P., Radwan, J., Axelson, D. A., … Phillips, M. L. (2011). Differential patterns of abnormal activity and connectivity in the amygdala–prefrontal circuitry in bipolar-I and bipolar-NOS youth. Journal of the American Academy of Child & Adolescent Psychiatry, 50(12), 1275–1289. doi:10.1016/j.jaac.2011.09.023CrossRefGoogle Scholar
Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (1997). International affective picture system (IAPS): Technical manual and affective ratings. NIMH Center for the Study of Emotion and Attention, pp. 39–58.Google Scholar
Leboyer, M., Bellivier, F., Nosten-Bertrand, M., Jouvent, R., Pauls, D., & Mallet, J. (1998). Psychiatric genetics: Search for phenotypes. Trends in Neurosciences, 21, 102–105.CrossRefGoogle ScholarPubMed
Meluken, I., Ottesen, N. M., Phan, K. L., Goldin, P. R., Di Simplicio, M., Macoveanu, J., … Miskowiak, K. W. (2018). Neural response during emotion regulation in monozygotic twins at high familial risk of affective disorders. NeuroImage: Clinical, 21, 101598.CrossRefGoogle Scholar
Miskowiak, K. W., Kjærstad, H. L., Meluken, I., Petersen, J. Z., Maciel, B. R., Köhler, C. A., … Carvalho, A. F. (2017). The search for neuroimaging and cognitive endophenotypes: A critical systematic review of studies involving unaffected first-degree relatives of individuals with bipolar disorder. Neuroscience and Biobehavioral Reviews, 73, 1–22. doi:10.1016/j.neubiorev.2016.12.011CrossRefGoogle ScholarPubMed
Morris, R., Sparks, A., Mitchell, P., Weickert, C., & Green, M. (2012). Lack of cortico-limbic coupling in bipolar disorder and schizophrenia during emotion regulation. Translational Psychiatry, 2(3), e90.CrossRefGoogle ScholarPubMed
Nelson, H. E., & O'Connell, A. (1978). Dementia: The estimation of premorbid intelligence levels using the new adult reading test. Cortex; A Journal Devoted to the Study of the Nervous System and Behavior, 14, 234–244.CrossRefGoogle ScholarPubMed
Njau, S., Townsend, J.,Wade, B., Hellemann, G., Bookheimer, S., Narr, K., … Brooks, J. O. III (2020). Neural subtypes of euthymic bipolar I disorder characterized by emotion-regulation circuitry. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 5, 591–600.Google ScholarPubMed
Ochsner, K. N., Bunge, S. A., Gross, J. J., & Gabrieli, J. D. (2002). Rethinking feelings: An FMRI study of the cognitive regulation of emotion. Journal of Cognitive Neuroscience, 14(8), 1215–1229.CrossRefGoogle ScholarPubMed
Ochsner, K. N., Silvers, J. A., & Buhle, J. T. (2012). Functional imaging studies of emotion regulation: A synthetic review and evolving model of the cognitive control of emotion. Annals of the New York Academy of Sciences, 1251, E1–24. doi:10.1111/j.1749-6632.2012.06751.xCrossRefGoogle ScholarPubMed
O'Reilly, J. X., Woolrich, M. W., Behrens, T. E., Smith, S. M., & Johansen-Berg, H. (2012). Tools of the trade: Psychophysiological interactions and functional connectivity. Social Cognitive and Affective Neuroscience, 7(5), 604–609.CrossRefGoogle ScholarPubMed
Ottesen, N. M., Meluken, I., Scheike, T., Kessing, L. V., Miskowiak, K. W., & Vinberg, M. (2018). Clinical characteristics, life adversities and personality traits in monozygotic twins with, at risk of and without affective disorders. Frontiers in Psychiatry, 9, 401.CrossRefGoogle ScholarPubMed
Passarotti, A. M., Ellis, J., Wegbreit, E., Stevens, M. C., & Pavuluri, M. N. (2012). Reduced functional connectivity of prefrontal regions and amygdala within affect and working memory networks in pediatric bipolar disorder. Brain Connectivity, 2(6), 320–334.CrossRefGoogle ScholarPubMed
Phan, K. L., Fitzgerald, D. A., Nathan, P. J., Moore, G. J., Uhde, T. W., & Tancer, M. E. (2005). Neural substrates for voluntary suppression of negative affect: A functional magnetic resonance imaging study. Biological Psychiatry, 57(3), 210–219.CrossRefGoogle ScholarPubMed
Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48(2), 175–187.CrossRefGoogle ScholarPubMed
Phillips, M. L., Ladouceur, C. D., & Drevets, W. C. (2008). A neural model of voluntary and automatic emotion regulation: Implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry, 13(9), 833.CrossRefGoogle ScholarPubMed
Picó-Pérez, M., Radua, J., Steward, T., Menchón, J. M., & Soriano-Mas, C. (2017). Emotion regulation in mood and anxiety disorders: A meta-analysis of fMRI cognitive reappraisal studies. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 79, 96–104.CrossRefGoogle ScholarPubMed
Rive, M. M., Mocking, R. J. T., Koeter, M. W. J., van Wingen, G., de Wit, S. J., van den Heuvel, O. A., … Schene, A. H. (2015). State-dependent differences in emotion regulation between unmedicated bipolar disorder and major depressive disorder. JAMA Psychiatry, 72, 687. doi:10.1001/jamapsychiatry.2015.0161CrossRefGoogle ScholarPubMed
Sankar, A., Purves, K., Colic, L., Lippard, E. T. C., Millard, H., Fan, S., … Constable, R. T. (2020). Altered frontal cortex functioning in emotion regulation and hopelessness in bipolar disorder. Bipolar Disorders, 23, 152–164.CrossRefGoogle ScholarPubMed
Snitz, B. E. (2005). Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: A meta-analytic review of putative endophenotypes. Schizophrenia Bulletin, 32(1), 179–194. doi:10.1093/schbul/sbi048CrossRefGoogle ScholarPubMed
Souza-Queiroz, J., Boisgontier, J., Etain, B., Poupon, C., Duclap, D., d'Albis, M.-A., … Delavest, M. (2016). Childhood trauma and the limbic network: A multimodal MRI study in patients with bipolar disorder and controls. Journal of Affective Disorders, 200, 159–164.CrossRefGoogle ScholarPubMed
Townsend, J., & Altshuler, L. L. (2012). Emotion processing and regulation in bipolar disorder: A review. Bipolar Disorders, 14(4), 326–339.CrossRefGoogle ScholarPubMed
Townsend, J. D., Torrisi, S. J., Lieberman, M. D., Sugar, C. A., Bookheimer, S. Y., & Altshuler, L. L. (2013). Frontal-amygdala connectivity alterations during emotion downregulation in bipolar I disorder. Biological Psychiatry, 73(2), 127–135.CrossRefGoogle ScholarPubMed
Wiggins, J. L., Brotman, M. A., Adleman, N. E., Kim, P., Wambach, C. G., Reynolds, R. C., … Leibenluft, E. (2017). Neural markers in pediatric bipolar disorder and familial risk for bipolar disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 56(1), 67–78. doi:10.1016/j.jaac.2016.10.009CrossRefGoogle ScholarPubMed
Wing, J. K., Babor, T., Brugha, T., Burke, J., Cooper, J. E., Giel, R., … Sartorius, N. (1990). SCAN. Schedules for clinical assessment in neuropsychiatry. Archives of General Psychiatry, 47(6), 589–593.CrossRefGoogle ScholarPubMed
Woolrich, M. W., Behrens, T. E., Beckmann, C. F., Jenkinson, M., & Smith, S. M. (2004). Multilevel linear modelling for FMRI group analysis using Bayesian inference. Neuroimage, 21(4), 1732–1747.CrossRefGoogle ScholarPubMed
Woolrich, M. W., Ripley, B. D., Brady, M., & Smith, S. M. (2001). Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage, 14(6), 1370–1386.CrossRefGoogle ScholarPubMed
World Health Organization. (1992). The ICD-10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines. Geneva: World Health Organization.Google Scholar
Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978). A rating scale for mania: Reliability, validity and sensitivity. The British Journal of Psychiatry, 133(5), 429–435. doi:10.1192/bjp.133.5.429CrossRefGoogle ScholarPubMed
Zhang, L., Ai, H., Opmeer, E. M., Marsman, J.-B. C., van der Meer, L., Ruhé, H. G., … Van Tol, M.-J. (2020). Distinct temporal brain dynamics in bipolar disorder and schizophrenia during emotion regulation. Psychological Medicine, 50(3), 413–421.CrossRefGoogle ScholarPubMed
Zilverstand, A., Parvaz, M. A., & Goldstein, R. Z. (2017). Neuroimaging cognitive reappraisal in clinical populations to define neural targets for enhancing emotion regulation. A systematic review. Neuroimage, 151, 105–116.CrossRefGoogle ScholarPubMed
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