Skip to main content Accessibility help
×
Home

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

  • S. Lui (a1), L. Yao (a1), Y. Xiao (a1), S. K. Keedy (a2), J. L. Reilly (a3), R. S. Keefe (a4), C. A. Tamminga (a5), M. S. Keshavan (a6), G. D. Pearlson (a7), Q. Gong (a1) and J. A. Sweeney (a5)...

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.

Copyright

Corresponding author

* 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: qiyonggong@hmrrc.org.cn) [Q.G.] (Email: 2323008200@qq.com) [S.L.]

References

Hide All
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, 99859990.
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, 13451347.
Bora, E, Fornito, A, Yucel, M, Pantelis, C (2010). Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biological Psychiatry 67, 10971105.
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.
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, 20092017.
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.
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, 13261333.
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.
Ellison-Wright, I, Bullmore, E (2010). Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophrenia Research 117, 112.
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, 3037.
Friston, KJ (1994). Functional and effective connectivity in neuroimaging: a synthesis. Human Brain Mapping 2, 5678.
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, 761768.
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, 12751284.
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, 89398944.
Houenou, J, d'Albis, MA, Vederine, FE, Henry, C, Leboyer, M, Wessa, M (2012). Neuroimaging biomarkers in bipolar disorder. Frontiers in Bioscience 4, 593606.
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, 897921.
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, 1623.
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, 458466.
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, 373378.
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, 257264.
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, 346353.
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, 234239.
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, 469477.
Logothetis, NK, Pauls, J, Augath, M, Trinath, T, Oeltermann, A (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature 412, 150157.
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, 196205.
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, 1541215417.
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, 783792.
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, 642648.
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, 378384.
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, 881889.
Medoff, DR, Holcomb, HH, Lahti, AC, Tamminga, CA (2001). Probing the human hippocampus using rCBF: contrasts in schizophrenia. Hippocampus 11, 543550.
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, 811822.
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, 759765.
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, 180195.
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, 5968.
Phillips, ML, Travis, MJ, Fagiolini, A, Kupfer, DJ (2008). Medication effects in neuroimaging studies of bipolar disorder. American Journal of Psychiatry 165, 313320.
Poldrack, RA (2007). Region of interest analysis for fMRI. Social Cognitive and Affective Neuroscience 2, 6770.
Rolls, ET (1996). The orbitofrontal cortex. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 351, 14331444.
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, 22092229.
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, 13251336.
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, 698708.
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, 454468.
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, 12631274.
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, 20052012.
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, 6678.
Welsh, RC, Chen, AC, Taylor, SF (2010). Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia. Schizophrenia Bulletin 36, 713722.
Wessa, M, Linke, J (2009). Emotional processing in bipolar disorder: behavioural and neuroimaging findings. International Review of Psychiatry 21, 357367.
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, 478490.
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.
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, 155158.
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, 8391.

Keywords

Related content

Powered by UNSILO
Type Description Title
WORD
Supplementary materials

Lui Supplementary Material
Tables S1–S5

 Word (251 KB)
251 KB

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

  • S. Lui (a1), L. Yao (a1), Y. Xiao (a1), S. K. Keedy (a2), J. L. Reilly (a3), R. S. Keefe (a4), C. A. Tamminga (a5), M. S. Keshavan (a6), G. D. Pearlson (a7), Q. Gong (a1) and J. A. Sweeney (a5)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.