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Brain functional changes in first-degree relatives of patients with bipolar disorder: evidence for default mode network dysfunction

Published online by Cambridge University Press:  23 June 2016

S. Alonso-Lana ,
M. Valentí ,
A. Romaguera ,
C. Sarri ,
S. Sarró ,
A. Rodríguez-Martínez ,
J. M. Goikolea ,
B. L. Amann ,
T. Maristany  and
R. Salvador
...Show all authors
S. Alonso-Lana*
Affiliation:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain
M. Valentí
Affiliation:
Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
A. Romaguera
Affiliation:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
C. Sarri
Affiliation:
Benito Menni Complex Assistencial en Salut Mental, Barcelona, Spain
S. Sarró
Affiliation:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
A. Rodríguez-Martínez
Affiliation:
Parc de Salut Mar, Barcelona, Spain
J. M. Goikolea
Affiliation:
Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
B. L. Amann
Affiliation:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
T. Maristany
Affiliation:
Hospital Sant Joan de Déu Infantil, Barcelona, Spain
R. Salvador
Affiliation:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
E. Vieta
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
P. J. McKenna
Affiliation:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
E. Pomarol-Clotet
Affiliation:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
*
*Address for correspondence: S. Alonso-Lana, FIDMAG Germanes Hospitalàries Research Foundation, C/Dr Antoni Pujades, 38, E-08830 Sant Boi de Llobregat, Barcelona, Spain. (Email: salonso@fidmag.com)
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Abstract

Background

Relatively few studies have investigated whether relatives of patients with bipolar disorder show brain functional changes, and these have focused on activation changes. Failure of de-activation during cognitive task performance is also seen in the disorder and may have trait-like characteristics since it has been found in euthymia.

Method

A total of 20 euthymic patients with bipolar disorder, 20 of their unaffected siblings and 40 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance (ANOVA) was fitted to individual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significant difference among the groups were used as regions of interest to compare mean activations/de-activations between them.

Results

A single cluster of significant difference among the three groups was found in the whole-brain ANOVA. This was located in the medial prefrontal cortex, a region of task-related de-activation in the healthy controls. Both the patients and their siblings showed significantly reduced de-activation compared with the healthy controls in this region, but the failure was less marked in the relatives.

Conclusions

Failure to de-activate the medial prefrontal cortex in both euthymic bipolar patients and their unaffected siblings adds to evidence for default mode network dysfunction in the disorder, and suggests that it may act as a trait marker.

Keywords

Bipolar disorderdefault mode networkeuthymiafirst-degree relativesfunctional magnetic resonance imaging
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 12 , September 2016 , pp. 2513 - 2521
Copyright
Copyright © Cambridge University Press 2016 

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References

Allin, MP, Marshall, N, Schulze, K, Walshe, M, Hall, MH, Picchioni, M, Murray, RM, McDonald, C (2010). A functional MRI study of verbal fluency in adults with bipolar disorder and their unaffected relatives. Psychological Medicine 40, 2025–2035.Google Scholar
Bellack, AS, Green, MF, Cook, JA, Fenton, W, Harvey, PD, Heaton, RK, Laughren, T, Leon, AC, Mayo, DJ, Patrick, DL, Patterson, TL, Rose, A, Stover, E, Wykes, T (2007). Assessment of community functioning in people with schizophrenia and other severe mental illnesses: a white paper based on an NIMH-sponsored workshop. Schizophrenia Bulletin 33, 805–822.Google Scholar
Broyd, SJ, Demanuele, C, Debener, S, Helps, SK, James, CJ, Sonuga-Barke, EJ (2009). Default-mode brain dysfunction in mental disorders: a systematic review. Neuroscience and Biobehavioral Reviews 33, 279–296.Google Scholar
Buckner, RL, Andrews-Hanna, JR, Schacter, DL (2008). The brain's default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences 1124, 1–38.Google Scholar
Calhoun, VD, Maciejewski, PK, Pearlson, GD, Kiehl, KA (2008). Temporal lobe and “default” hemodynamic brain modes discriminate between schizophrenia and bipolar disorder. Human Brain Mapping 29, 1265–1275.Google Scholar
Chen, CH, Suckling, J, Lennox, BR, Ooi, C, Bullmore, ET (2011). A quantitative meta-analysis of fMRI studies in bipolar disorder. Bipolar Disorder 13, 1–15.Google Scholar
Costafreda, SG, Fu, CH, Picchioni, M, Toulopoulou, T, McDonald, C, Kravariti, E, Walshe, M, Prata, D, Murray, RM, McGuire, PK (2011). Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder. BMC Psychiatry 11, 18.CrossRefGoogle ScholarPubMed
Craddock, N, Sklar, P (2013). Genetics of bipolar disorder. Lancet 381, 1654–1662.Google Scholar
Cremaschi, L, Penzo, B, Palazzo, M, Dobrea, C, Cristoffanini, M, Dell'Osso, B, Altamura, AC (2013). Assessing working memory via N-back task in euthymic bipolar I disorder patients: a review of functional magnetic resonance imaging studies. Neuropsychobiology 68, 63–70.Google Scholar
Del Ser, T, Gonzalez-Montalvo, JI, Martinez-Espinosa, S, Delgado-Villapalos, C, Bermejo, F (1997). Estimation of premorbid intelligence in Spanish people with the Word Accentuation Test and its application to the diagnosis of dementia. Brain and Cognition 33, 343–356.Google Scholar
Drapier, D, Surguladze, S, Marshall, N, Schulze, K, Fern, A, Hall, MH, Walshe, M, Murray, RM, McDonald, C (2008). Genetic liability for bipolar disorder is characterized by excess frontal activation in response to a working memory task. Biological Psychiatry 64, 513–520.Google Scholar
Fernandez-Corcuera, P, Salvador, R, Monte, GC, Salvador Sarro, S, Goikolea, JM, Amann, B, Moro, N, Sans-Sansa, B, Ortiz-Gil, J, Vieta, E, Maristany, T, McKenna, PJ, Pomarol-Clotet, E (2013). Bipolar depressed patients show both failure to activate and failure to de-activate during performance of a working memory task. Journal of Affective Disorders 148, 170–178.Google Scholar
Frodl, T, Scheuerecker, J, Albrecht, J, Kleemann, AM, Muller-Schunk, S, Koutsouleris, N, Moller, HJ, Bruckmann, H, Wiesmann, M, Meisenzahl, E (2009). Neuronal correlates of emotional processing in patients with major depression. World Journal of Biological Psychiatry 10, 202–208.CrossRefGoogle ScholarPubMed
Gevins, A, Cutillo, B (1993). Spatiotemporal dynamics of component processes in human working memory. Electroencephalography and Clinical Neurophysiology 87, 128–143.Google Scholar
Gomar, JJ, Ortiz-Gil, J, McKenna, PJ, Salvador, R, Sans-Sansa, B, Sarro, S, Guerrero, A, Pomarol-Clotet, E (2011). Validation of the Word Accentuation Test (TAP) as a means of estimating premorbid IQ in Spanish speakers. Schizophrenia Research 128, 175–176.Google Scholar
Green, DM, Swets, JA (1966). Signal Detection Theory and Psychophysics. Krieger: New York.Google Scholar
Grimm, S, Boesiger, P, Beck, J, Schuepbach, D, Bermpohl, F, Walter, M, Ernst, J, Hell, D, Boeker, H, Northoff, G (2009). Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology 34, 932–943.Google Scholar
Gusnard, DA, Raichle, ME (2001). Searching for a baseline: functional imaging and the resting human brain. Nature Reviews Neuroscience 2, 685–694.Google Scholar
Hafeman, DM, Chang, KD, Garrett, AS, Sanders, EM, Phillips, ML (2012). Effects of medication on neuroimaging findings in bipolar disorder: an updated review. Bipolar Disorder 14, 375–410.Google Scholar
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 56–62.Google Scholar
Jastak, S, Wilkinson, GS (1984). The Wide Range Achievement Test–Revised Administration Manual. Jastak Associates: Wilmington, DE.Google Scholar
Kanske, P, Heissler, J, Schonfelder, S, Forneck, J, Wessa, M (2013). Neural correlates of emotional distractibility in bipolar disorder patients, unaffected relatives, and individuals with hypomanic personality. American Journal of Psychiatry 170, 1487–1496.Google Scholar
Kupferschmidt, DA, Zakzanis, KK (2011). Toward a functional neuroanatomical signature of bipolar disorder: quantitative evidence from the neuroimaging literature. Psychiatry Research 193, 71–79.Google Scholar
Linke, J, King, AV, Rietschel, M, Strohmaier, J, Hennerici, M, Gass, A, Meyer-Lindenberg, A, Wessa, M (2012). Increased medial orbitofrontal and amygdala activation: evidence for a systems-level endophenotype of bipolar I disorder. American Journal of Psychiatry 169, 316–325.Google Scholar
McGuffin, P, Rijsdijk, F, Andrew, M, Sham, P, Katz, R, Cardno, A (2003). The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Archives of General Psychiatry 60, 497–502.Google Scholar
Nelson, HE, Willison, JR (1991). The Revised National Adult Reading Test. NFER-Nelson: Windsor.Google Scholar
Poldrack, RA (2007). Region of interest analysis for fMRI. Social Cognitive and Affective Neuroscience 2, 67–70.Google Scholar
Pomarol-Clotet, E, Alonso-Lana, S, Moro, N, Sarro, S, Bonnin, MC, Goikolea, JM, Fernandez-Corcuera, P, Amann, BL, Romaguera, A, Vieta, E, Blanch, J, McKenna, PJ, Salvador, R (2015). Brain functional changes across the different phases of bipolar disorder. British Journal of Psychiatry 206, 136–144.Google Scholar
Pomarol-Clotet, E, Salvador, R, Sarro, S, Gomar, J, Vila, F, Martinez, A, Guerrero, A, Ortiz-Gil, J, Sans-Sansa, B, Capdevila, A, Cebamanos, JM, McKenna, PJ (2008). Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network? Psychological Medicine 38, 1185–1193.Google Scholar
Pompei, F, Jogia, J, Tatarelli, R, Girardi, P, Rubia, K, Kumari, V, Frangou, S (2011). Familial and disease specific abnormalities in the neural correlates of the Stroop Task in bipolar disorder. NeuroImage 56, 1677–1684.Google Scholar
Price, JL, Drevets, WC (2012). Neural circuits underlying the pathophysiology of mood disorders. Trends in Cognitive Sciences 16, 61–71.Google Scholar
Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL (2001). A default mode of brain function. Proceedings of the National Academy of Sciences of the USA 98, 676–682.Google Scholar
Roberts, G, Green, MJ, Breakspear, M, McCormack, C, Frankland, A, Wright, A, Levy, F, Lenroot, R, Chan, HN, Mitchell, PB (2013). Reduced inferior frontal gyrus activation during response inhibition to emotional stimuli in youth at high risk of bipolar disorder. Biological Psychiatry 74, 55–61.Google Scholar
Robins, LN, Cottler, LB, Bucholz, KK, Compton, WM, North, CS, Rourke, K (2000). Computerized Diagnostic Interview Schedule for the DSM-IV (C DIS-IV). NIMH/University of Florida: Gainesville, FL.Google Scholar
Savitz, J, Drevets, WC (2009). Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neuroscience and Biobehavioral Reviews 33, 699–771.Google Scholar
Sepede, G, De Berardis, D, Campanella, D, Perrucci, MG, Ferretti, A, Serroni, N, Moschetta, FS, Del Gratta, C, Salerno, RM, Ferro, FM, Di Giannantonio, M, Onofrj, M, Romani, GL, Gambi, F (2012). Impaired sustained attention in euthymic bipolar disorder patients and non-affected relatives: an fMRI study. Bipolar Disorder 14, 764–779.Google Scholar
Sheline, YI, Barch, DM, Price, JL, Rundle, MM, Vaishnavi, SN, Snyder, AZ, Mintun, MA, Wang, S, Coalson, RS, Raichle, ME (2009). The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences of the USA 106, 1942–1947.Google Scholar
Smith, SM, Jenkinson, M, Woolrich, MW, Beckmann, CF, Behrens, TE, Johansen-Berg, H, Bannister, PR, De Luca, M, Drobnjak, I, Flitney, DE, Niazy, RK, Saunders, J, Vickers, J, Zhang, Y, De Stefano, N, Brady, JM, Matthews, PM (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23 (Suppl. 1), S208–S219.Google Scholar
Strakowski, SM, Adler, CM, Almeida, J, Altshuler, LL, Blumberg, HP, Chang, KD, DelBello, MP, Frangou, S, McIntosh, A, Phillips, ML, Sussman, JE, Townsend, JD (2012). The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disorder 14, 313–325.Google Scholar
Strakowski, SM, Delbello, MP, Adler, CM (2005). The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Molecular Psychiatry 10, 105–116.Google Scholar
Surguladze, SA, Marshall, N, Schulze, K, Hall, MH, Walshe, M, Bramon, E, Phillips, ML, Murray, RM, McDonald, C (2010). Exaggerated neural response to emotional faces in patients with bipolar disorder and their first-degree relatives. NeuroImage 53, 58–64.Google Scholar
Thermenos, HW, Goldstein, JM, Milanovic, SM, Whitfield-Gabrieli, S, Makris, N, Laviolette, P, Koch, JK, Faraone, SV, Tsuang, MT, Buka, SL, Seidman, LJ (2010). An fMRI study of working memory in persons with bipolar disorder or at genetic risk for bipolar disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 153B, 120–131.Google Scholar
Townsend, J, Bookheimer, SY, Foland-Ross, LC, Sugar, CA, Altshuler, LL (2010). fMRI abnormalities in dorsolateral prefrontal cortex during a working memory task in manic, euthymic and depressed bipolar subjects. Psychiatry Research 182, 22–29.Google Scholar
Whalley, HC, Sussmann, JE, Chakirova, G, Mukerjee, P, Peel, A, McKirdy, J, Hall, J, Johnstone, EC, Lawrie, SM, McIntosh, AM (2011). The neural basis of familial risk and temperamental variation in individuals at high risk of bipolar disorder. Biological Psychiatry 70, 343–349.Google Scholar
Whitfield-Gabrieli, S, Moran, JM, Nieto-Castanon, A, Triantafyllou, C, Saxe, R, Gabrieli, JD (2011). Associations and dissociations between default and self-reference networks in the human brain. NeuroImage 55, 225–232.Google Scholar
Young, RC, Biggs, JT, Ziegler, VE, Meyer, DA (1978). A rating scale for mania: reliability, validity and sensitivity. British Journal of Psychiatry 133, 429–435.Google Scholar