Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-19T14:05:55.891Z Has data issue: false hasContentIssue false
  • English
  • Français

Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives

Published online by Cambridge University Press:  20 May 2014

S. Lui ,
L. Yao ,
Y. Xiao ,
S. K. Keedy ,
J. L. Reilly ,
R. S. Keefe ,
C. A. Tamminga ,
M. S. Keshavan ,
G. D. Pearlson  and
Q. Gong
...Show all authors
S. Lui*
Affiliation:
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China
L. Yao
Affiliation:
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China
Y. Xiao
Affiliation:
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China
S. K. Keedy
Affiliation:
Department of Psychiatry, University of Chicago, Chicago, IL, USA
J. L. Reilly
Affiliation:
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
R. S. Keefe
Affiliation:
Department of Psychiatry, Duke University Medical Center, Durham, IL, USA
C. A. Tamminga
Affiliation:
Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA
M. S. Keshavan
Affiliation:
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
G. D. Pearlson
Affiliation:
Departments of Psychiatry and Neurobiology, Yale University School of Medicine and Olin Neuropsychiatric Research Center, Hartford, CT, USA
Q. Gong*
Affiliation:
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China
J. A. Sweeney
Affiliation:
Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA
*
*Address for correspondence: Q. Gong, Ph.D., M.D., Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, No. 37 GuoXue Alley, Chengdu 610041, People's Republic of China. (Email: [email protected]) [Q.G.] (Email: [email protected]) [S.L.]
*Address for correspondence: Q. Gong, Ph.D., M.D., Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, No. 37 GuoXue Alley, Chengdu 610041, People's Republic of China. (Email: [email protected]) [Q.G.] (Email: [email protected]) [S.L.]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified.

Method

A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives.

Results

SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups.

Conclusions

The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.

Keywords

Bipolar disorderbrain functionmagnetic resonance imagingrelativesresting stateschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 1 , January 2015 , pp. 97 - 108
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andreasen, NC, O'Leary, DS, Cizadlo, T, Arndt, S, Rezai, K, Ponto, LL, Watkins, GL, Hichwa, RD (1996). Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proceedings of the National Academy of Sciences USA 93, 9985–9990.CrossRefGoogle ScholarPubMed
Blumberg, HP, Martin, A, Kaufman, J, Leung, HC, Skudlarski, P, Lacadie, C, Fulbright, RK, Gore, JC, Charney, DS, Krystal, JH, Peterson, BS (2003). Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI. American Journal of Psychiatry 160, 1345–1347.CrossRefGoogle ScholarPubMed
Bora, E, Fornito, A, Yucel, M, Pantelis, C (2010). Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biological Psychiatry 67, 1097–1105.CrossRefGoogle ScholarPubMed
Calhoun, VD, Sui, J, Kiehl, K, Turner, J, Allen, E, Pearlson, G (2011). Exploring the psychosis functional connectome: aberrant intrinsic networks in schizophrenia and bipolar disorder. Frontiers in Psychiatry 2, 75.Google ScholarPubMed
Chai, XJ, Whitfield-Gabrieli, S, Shinn, AK, Gabrieli, JD, Nieto Castanon, A, McCarthy, JM, Cohen, BM, Ongur, D (2011). Abnormal medial prefrontal cortex resting-state connectivity in bipolar disorder and schizophrenia. Neuropsychopharmacology 36, 2009–2017.CrossRefGoogle Scholar
Cole, DM, Smith, SM, Beckmann, CF (2010). Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Frontiers in Systems Neuroscience 4, 8.Google ScholarPubMed
Cordes, D, Haughton, VM, Arfanakis, K, Carew, JD, Turski, PA, Moritz, CH, Quigley, MA, Meyerand, ME (2001). Frequencies contributing to functional connectivity in the cerebral cortex in “resting-state” data. American Journal of Neuroradiology 22, 1326–1333.Google ScholarPubMed
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
Ellison-Wright, I, Bullmore, E (2010). Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophrenia Research 117, 1–12.CrossRefGoogle ScholarPubMed
Filippi, M, Canu, E, Gasparotti, R, Agosta, F, Valsecchi, P, Lodoli, G, Galluzzo, A, Comi, G, Sacchetti, E (2013). Patterns of brain structural changes in first-contact, antipsychotic drug-naive patients with schizophrenia. American Journal of Neuroradiology 35, 30–37.CrossRefGoogle ScholarPubMed
Friston, KJ (1994). Functional and effective connectivity in neuroimaging: a synthesis. Human Brain Mapping 2, 56–78.CrossRefGoogle Scholar
Gur, RE, Cowell, PE, Latshaw, A, Turetsky, BI, Grossman, RI, Arnold, SE, Bilker, WB, Gur, RC (2000). Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia. Archives of General Psychiatry 57, 761–768.Google ScholarPubMed
Hill, SK, Reilly, JL, Keefe, RS, Gold, JM, Bishop, JR, Gershon, ES, Tamminga, CA, Pearlson, GD, Keshavan, MS, Sweeney, JA (2013). Neuropsychological impairments in schizophrenia and psychotic bipolar disorder: findings from the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study. American Journal of Psychiatry 170, 1275–1284.CrossRefGoogle ScholarPubMed
Horwitz, B, Rumsey, JM, Donohue, BC (1998). Functional connectivity of the angular gyrus in normal reading and dyslexia. Proceedings of the National Academy of Sciences USA 95, 8939–8944.CrossRefGoogle ScholarPubMed
Houenou, J, d'Albis, MA, Vederine, FE, Henry, C, Leboyer, M, Wessa, M (2012). Neuroimaging biomarkers in bipolar disorder. Frontiers in Bioscience 4, 593–606.CrossRefGoogle ScholarPubMed
Ivleva, EI, Morris, DW, Moates, AF, Suppes, T, Thaker, GK, Tamminga, CA (2010). Genetics and intermediate phenotypes of the schizophrenia–bipolar disorder boundary. Neuroscience and Biobehavioral Reviews 34, 897–921.CrossRefGoogle ScholarPubMed
Keedy, SK, Rosen, C, Khine, T, Rajarethinam, R, Janicak, PG, Sweeney, JA (2009). An fMRI study of visual attention and sensorimotor function before and after antipsychotic treatment in first-episode schizophrenia. Psychiatry Research 172, 16–23.CrossRefGoogle ScholarPubMed
Khadka, S, Meda, SA, Stevens, MC, Glahn, DC, Calhoun, VD, Sweeney, JA, Tamminga, CA, Keshavan, MS, O'Neil, K, Schretlen, D, Pearlson, GD (2013). Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study. Biological Psychiatry 74, 458–466.CrossRefGoogle ScholarPubMed
Kiviniemi, V, Jauhiainen, J, Tervonen, O, Paakko, E, Oikarinen, J, Vainionpaa, V, Rantala, H, Biswal, B (2000). Slow vasomotor fluctuation in fMRI of anesthetized child brain. Magnetic Resonance in Medicine 44, 373–378.Google ScholarPubMed
Kruger, S, Alda, M, Young, LT, Goldapple, K, Parikh, S, Mayberg, HS (2006). Risk and resilience markers in bipolar disorder: brain responses to emotional challenge in bipolar patients and their healthy siblings. American Journal of Psychiatry 163, 257–264.CrossRefGoogle ScholarPubMed
Kyriakopoulos, M, Perez-Iglesias, R, Woolley, JB, Kanaan, RA, Vyas, NS, Barker, GJ, Frangou, S, McGuire, PK (2009). Effect of age at onset of schizophrenia on white matter abnormalities. British Journal of Psychiatry 195, 346–353.CrossRefGoogle ScholarPubMed
Lichtenstein, P, Yip, BH, Bjork, C, Pawitan, Y, Cannon, TD, Sullivan, PF, Hultman, CM (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234–239.CrossRefGoogle ScholarPubMed
Liu, H, Tang, Y, Womer, F, Fan, G, Lu, T, Driesen, N, Ren, L, Wang, Y, He, Y, Blumberg, HP, Xu, K, Wang, F (2014). Differentiating patterns of amygdala-frontal functional connectivity in schizophrenia and bipolar disorder. Schizophrenia Bulletin 40, 469–477.CrossRefGoogle ScholarPubMed
Logothetis, NK, Pauls, J, Augath, M, Trinath, T, Oeltermann, A (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature 412, 150–157.CrossRefGoogle ScholarPubMed
Lui, S, Deng, W, Huang, X, Jiang, L, Ma, X, Chen, H, Zhang, T, Li, X, Li, D, Zou, L, Tang, H, Zhou, XJ, Mechelli, A, Collier, DA, Sweeney, JA, Li, T, Gong, Q (2009 a). Association of cerebral deficits with clinical symptoms in antipsychotic-naive first-episode schizophrenia: an optimized voxel-based morphometry and resting state functional connectivity study. American Journal of Psychiatry 166, 196–205.CrossRefGoogle ScholarPubMed
Lui, S, Huang, X, Chen, L, Tang, H, Zhang, T, Li, X, Li, D, Kuang, W, Chan, RC, Mechelli, A, Sweeney, JA, Gong, Q (2009 b). High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China. Proceedings of the National Academy of Sciences USA 106, 15412–15417.CrossRefGoogle ScholarPubMed
Lui, S, Li, T, Deng, W, Jiang, L, Wu, Q, Tang, H, Yue, Q, Huang, X, Chan, RC, Collier, DA, Meda, SA, Pearlson, G, Mechelli, A, Sweeney, JA, Gong, Q (2010). Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by “resting state” functional magnetic resonance imaging. Archives of General Psychiatry 67, 783–792.CrossRefGoogle ScholarPubMed
Lui, S, Wu, Q, Qiu, L, Yang, X, Kuang, W, Chan, RC, Huang, X, Kemp, GJ, Mechelli, A, Gong, Q (2011). Resting-state functional connectivity in treatment-resistant depression. American Journal of Psychiatry 168, 642–648.CrossRefGoogle ScholarPubMed
McIntosh, AM, Whalley, HC, McKirdy, J, Hall, J, Sussmann, JE, Shankar, P, Johnstone, EC, Lawrie, SM (2008). Prefrontal function and activation in bipolar disorder and schizophrenia. American Journal of Psychiatry 165, 378–384.Google Scholar
Meda, SA, Gill, A, Stevens, MC, Lorenzoni, RP, Glahn, DC, Calhoun, VD, Sweeney, JA, Tamminga, CA, Keshavan, MS, Thaker, G, Pearlson, GD (2012). Differences in resting-state functional magnetic resonance imaging functional network connectivity between schizophrenia and psychotic bipolar probands and their unaffected first-degree relatives. Biological Psychiatry 71, 881–889.CrossRefGoogle ScholarPubMed
Medoff, DR, Holcomb, HH, Lahti, AC, Tamminga, CA (2001). Probing the human hippocampus using rCBF: contrasts in schizophrenia. Hippocampus 11, 543–550.CrossRefGoogle ScholarPubMed
Minzenberg, MJ, Laird, AR, Thelen, S, Carter, CS, Glahn, DC (2009). Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Archives of General Psychiatry 66, 811–822.CrossRefGoogle ScholarPubMed
Mohamed, MA, Yousem, DM, Tekes, A, Browner, N, Calhoun, VD (2004). Correlation between the amplitude of cortical activation and reaction time: a functional MRI study. American Journal of Roentgenology 183, 759–765.CrossRefGoogle ScholarPubMed
Nakamura, M, Nestor, PG, Levitt, JJ, Cohen, AS, Kawashima, T, Shenton, ME, McCarley, RW (2008). Orbitofrontal volume deficit in schizophrenia and thought disorder. Brain 131, 180–195.CrossRefGoogle ScholarPubMed
Ongur, D, Lundy, M, Greenhouse, I, Shinn, AK, Menon, V, Cohen, BM, Renshaw, PF (2010). Default mode network abnormalities in bipolar disorder and schizophrenia. Psychiatry Research 183, 59–68.CrossRefGoogle Scholar
Phillips, ML, Travis, MJ, Fagiolini, A, Kupfer, DJ (2008). Medication effects in neuroimaging studies of bipolar disorder. American Journal of Psychiatry 165, 313–320.CrossRefGoogle ScholarPubMed
Poldrack, RA (2007). Region of interest analysis for fMRI. Social Cognitive and Affective Neuroscience 2, 67–70.CrossRefGoogle ScholarPubMed
Rolls, ET (1996). The orbitofrontal cortex. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 351, 1433–1444.Google ScholarPubMed
Shehzad, Z, Kelly, AM, Reiss, PT, Gee, DG, Gotimer, K, Uddin, LQ, Lee, SH, Margulies, DS, Roy, AK, Biswal, BB, Petkova, E, Castellanos, FX, Milham, MP (2009). The resting brain: unconstrained yet reliable. Cerebral Cortex 19, 2209–2229.CrossRefGoogle ScholarPubMed
Siegel, BV Jr., Buchsbaum, MS, Bunney, WE Jr., Gottschalk, LA, Haier, RJ, Lohr, JB, Lottenberg, S, Najafi, A, Nuechterlein, KH, Potkin, SG, et al. (1993). Cortical–striatal–thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients. American Journal of Psychiatry 150, 1325–1336.Google ScholarPubMed
Sweeney, JA, Luna, B, Srinivasagam, NM, Keshavan, MS, Schooler, NR, Haas, GL, Carl, JR (1998). Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields. Biological Psychiatry 44, 698–708.CrossRefGoogle ScholarPubMed
Sweeney, JA, Mintun, MA, Kwee, S, Wiseman, MB, Brown, DL, Rosenberg, DR, Carl, JR (1996). Positron emission tomography study of voluntary saccadic eye movements and spatial working memory. Journal of Neurophysiology 75, 454–468.CrossRefGoogle ScholarPubMed
Tamminga, CA, Ivleva, EI, Keshavan, MS, Pearlson, GD, Clementz, BA, Witte, B, Morris, DW, Bishop, J, Thaker, GK, Sweeney, JA (2013). Clinical phenotypes of psychosis in the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP). American Journal of Psychiatry 170, 1263–1274.CrossRefGoogle ScholarPubMed
Wang, F, Kalmar, JH, Womer, FY, Edmiston, EE, Chepenik, LG, Chen, R, Spencer, L, Blumberg, HP (2011). Olfactocentric paralimbic cortex morphology in adolescents with bipolar disorder. Brain 134, 2005–2012.CrossRefGoogle ScholarPubMed
Wang, L, Hosakere, M, Trein, JC, Miller, A, Ratnanather, JT, Barch, DM, Thompson, PA, Qiu, A, Gado, MH, Miller, MI, Csernansky, JG (2007). Abnormalities of cingulate gyrus neuroanatomy in schizophrenia. Schizophrenia Research 93, 66–78.CrossRefGoogle ScholarPubMed
Welsh, RC, Chen, AC, Taylor, SF (2010). Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia. Schizophrenia Bulletin 36, 713–722.CrossRefGoogle ScholarPubMed
Wessa, M, Linke, J (2009). Emotional processing in bipolar disorder: behavioural and neuroimaging findings. International Review of Psychiatry 21, 357–367.CrossRefGoogle ScholarPubMed
Whalley, HC, Simonotto, E, Flett, S, Marshall, I, Ebmeier, KP, Owens, DG, Goddard, NH, Johnstone, EC, Lawrie, SM (2004). fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia. Brain 127, 478–490.CrossRefGoogle ScholarPubMed
Yang, H, Long, XY, Yang, Y, Yan, H, Zhu, CZ, Zhou, XP, Zang, YF, Gong, QY (2007). Amplitude of low frequency fluctuation within visual areas revealed by resting-state functional MRI. Neuroimage 36, 144–52.Google ScholarPubMed
Yucel, M, Brewer, WJ, Harrison, BJ, Fornito, A, O'Keefe, GJ, Olver, J, Scott, AM, Egan, GF, Velakoulis, D, McGorry, PD, Pantelis, C (2007). Anterior cingulate activation in antipsychotic-naive first-episodeschizophrenia. Acta Psychiatrica Scandinavica 115, 155–158.CrossRefGoogle Scholar
Zang, YF, He, Y, Zhu, CZ, Cao, QJ, Sui, MQ, Liang, M, Tian, LX, Jiang, TZ, Wang, YF (2007). Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain and Development 29, 83–91.Google ScholarPubMed
Supplementary material: File

Lui Supplementary Material

Tables S1–S5

Download Lui Supplementary Material(File)
File 250.9 KB