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Risperidone-induced topological alterations of anatomical brain network in first-episode drug-naive schizophrenia patients: a longitudinal diffusion tensor imaging study

Published online by Cambridge University Press:  24 June 2016

M. Hu ,
X. Zong ,
J. Zheng ,
J. J. Mann ,
Z. Li ,
S. P. Pantazatos ,
Y. Li ,
Y. Liao ,
Y. He  and
J. Zhou
...Show all authors
M. Hu
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute and Departments of Psychiatry and Radiology, Columbia University, 1051 Riverside Drive, Box 42, New York, NY 10032, USA
X. Zong
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China
J. Zheng
Affiliation:
Key Laboratory for NeuroInformation of the Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, People's Republic of China
J. J. Mann
Affiliation:
Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute and Departments of Psychiatry and Radiology, Columbia University, 1051 Riverside Drive, Box 42, New York, NY 10032, USA
Z. Li
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China
S. P. Pantazatos
Affiliation:
Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute and Departments of Psychiatry, Columbia University, New York, NY 10032, USA
Y. Li
Affiliation:
Key Laboratory for NeuroInformation of the Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, People's Republic of China
Y. Liao
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China Department of Psychiatry and Biobehavioral Sciences, UCLA Semel Institute for Neuroscience, David Geffen School of Medicine, Los Angeles, CA 90024,USA
Y. He
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China
J. Zhou
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China
D. Sang
Affiliation:
Department of Radiology, Henan Mental Hospital, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, People's Republic of China
H. Zhao
Affiliation:
Department of Radiology, Henan Mental Hospital, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, People's Republic of China
J. Tang*
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China Department of Psychiatry and Biobehavioral Sciences, UCLA Semel Institute for Neuroscience, David Geffen School of Medicine, Los Angeles, CA 90024,USA
H. Chen*
Affiliation:
Key Laboratory for NeuroInformation of the Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, People's Republic of China
L. Lv*
Affiliation:
Department of Psychiatry, Henan Mental Hospital, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, People's Republic of China Henan Key Laboratory of Biological Psychiatry, Henan Mental Hospital, Xinxiang Medical University, Xinxiang, Henan 453002, People's Republic of China
X. Chen*
Affiliation:
Mental Health Institute of the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China The China National Clinical Research Center for Mental Health Disorders, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China National Technology Institute of Psychiatry, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China Key Laboratory of Psychiatry and Mental Health of Hunan Province, 139 Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China
*
*Address for correspondence: X. Chen, J. Tang, H. Chen and L. Lv, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. (Email: chenxghn@gmail.com; tangjinsonghn@gmail.com; chenhf@uestc.edu.cn; lvluxian@126.com)
*Address for correspondence: X. Chen, J. Tang, H. Chen and L. Lv, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. (Email: chenxghn@gmail.com; tangjinsonghn@gmail.com; chenhf@uestc.edu.cn; lvluxian@126.com)
*Address for correspondence: X. Chen, J. Tang, H. Chen and L. Lv, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. (Email: chenxghn@gmail.com; tangjinsonghn@gmail.com; chenhf@uestc.edu.cn; lvluxian@126.com)
*Address for correspondence: X. Chen, J. Tang, H. Chen and L. Lv, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. (Email: chenxghn@gmail.com; tangjinsonghn@gmail.com; chenhf@uestc.edu.cn; lvluxian@126.com)
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Abstract

Background

It remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.

Method

We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.

Results

Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.

Conclusions

During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.

Keywords

First-episode schizophrenialongitudinal studiesnetworksschizophreniatopologywhite matter
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 12 , September 2016 , pp. 2549 - 2560
Copyright
Copyright © Cambridge University Press 2016 

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References

Achard, S, Bullmore, E (2007). Efficiency and cost of economical brain functional networks. PLoS Computational Biology 3, e17.Google Scholar
Bohlken, MM, Mandl, RC, Brouwer, RM, van den Heuvel, MP, Hedman, AM, Kahn, RS, Hulshoff Pol, HE (2014). Heritability of structural brain network topology: a DTI study of 156 twins. Human Brain Mapping 35, 5295–5305.Google Scholar
Bullmore, E, Sporns, O (2012). The economy of brain network organization. Nature Reviews . Neuroscience 13, 336–349.Google Scholar
Carbonell, F, Nagano-Saito, A, Leyton, M, Cisek, P, Benkelfat, C, He, Y, Dagher, A (2014). Dopamine precursor depletion impairs structure and efficiency of resting state brain functional networks. Neuropharmacology 84, 90–100.Google Scholar
Carter, CS, MacDonald, AW 3rd, Ross, LL, Stenger, VA (2001). Anterior cingulate cortex activity and impaired self-monitoring of performance in patients with schizophrenia: an event-related fMRI study. American Journal of Psychiatry 158, 1423–1428.Google Scholar
Catani, M, Dell'Acqua, F, Thiebaut de Schotten, M (2013). A revised limbic system model for memory, emotion and behaviour. Neuroscience and Biobehavioral Reviews 37, 1724–1737.CrossRefGoogle ScholarPubMed
Cheng, H, Wang, Y, Sheng, J, Kronenberger, WG, Mathews, VP, Hummer, TA, Saykin, AJ (2012). Characteristics and variability of structural networks derived from diffusion tensor imaging. NeuroImage 61, 1153–1164.Google Scholar
Cheung, V, Chiu, CP, Law, CW, Cheung, C, Hui, CL, Chan, KK, Sham, PC, Deng, MY, Tai, KS, Khong, PL, McAlonan, GM, Chua, SE, Chen, E (2011). Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia. Psychological Medicine 41, 1709–1719.CrossRefGoogle ScholarPubMed
Collin, G, Kahn, RS, de Reus, MA, Cahn, W, van den Heuvel, MP (2014). Impaired rich club connectivity in unaffected siblings of schizophrenia patients. Schizophrenia Bulletin 40, 438–448.CrossRefGoogle ScholarPubMed
De Reus, MA, van den Heuvel, MP (2013). Estimating false positives and negatives in brain networks. NeuroImage 70, 402–409.Google Scholar
Ellison-Wright, I, Bullmore, E (2009). Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophrenia Research 108, 3–10.Google Scholar
Farkas, N, Lendeckel, U, Dobrowolny, H, Funke, S, Steiner, J, Keilhoff, G, Schmitt, A, Bogerts, B, Bernstein, HG (2010). Reduced density of ADAM 12-immunoreactive oligodendrocytes in the anterior cingulate white matter of patients with schizophrenia. World Journal of Biological Psychiatry: the Official Journal of the World Federation of Societies of Biological Psychiatry 11, 556–566.Google Scholar
Gur, RE, Loughead, J, Kohler, CG, Elliott, MA, Lesko, K, Ruparel, K, Wolf, DH, Bilker, WB, Gur, RC (2007). Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia. Archives of General Psychiatry 64, 1356–1366.CrossRefGoogle ScholarPubMed
Kates, WR, Olszewski, AK, Gnirke, MH, Kikinis, Z, Nelson, J, Antshel, KM, Fremont, W, Radoeva, PD, Middleton, FA, Shenton, ME, Coman, IL (2015). White matter microstructural abnormalities of the cingulum bundle in youths with 22q11.2 deletion syndrome: associations with medication, neuropsychological function, and prodromal symptoms of psychosis. Schizophrenia Research 161, 76–84.Google Scholar
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.Google Scholar
Kubicki, M, Westin, CF, Nestor, PG, Wible, CG, Frumin, M, Maier, SE, Kikinis, R, Jolesz, FA, McCarley, RW, Shenton, ME (2003). Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study. Biological Psychiatry 54, 1171–1180.Google Scholar
Lahti, AC, Weiler, MA, Holcomb, HH, Tamminga, CA, Cropsey, KL (2009). Modulation of limbic circuitry predicts treatment response to antipsychotic medication: a functional imaging study in schizophrenia. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 34, 2675–2690.Google Scholar
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.Google Scholar
Maddock, RJ (1999). The retrosplenial cortex and emotion: new insights from functional neuroimaging of the human brain. Trends in Neurosciences 22, 310–316.Google Scholar
Menon, V (2011). Large-scale brain networks and psychopathology: a unifying triple network model. Trends in Cognitive Sciences 15, 483–506.CrossRefGoogle ScholarPubMed
Meyer, U, Feldon, J (2009). Neural basis of psychosis-related behaviour in the infection model of schizophrenia. Behavioural Brain Research 204, 322–334.Google Scholar
Palaniyappan, L, Liddle, PF (2012). Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. Journal of Psychiatry and Neuroscience: JPN 37, 17–27.CrossRefGoogle ScholarPubMed
Palaniyappan, L, Mallikarjun, P, Joseph, V, White, TP, Liddle, PF (2011). Reality distortion is related to the structure of the salience network in schizophrenia. Psychological Medicine 41, 1701–1708.CrossRefGoogle Scholar
Palaniyappan, L, White, TP, Liddle, PF (2012). The concept of salience network dysfunction in schizophrenia: from neuroimaging observations to therapeutic opportunities. Current Topics in Medicinal Chemistry 12, 2324–2338.Google Scholar
Piantadosi, PT, Floresco, SB (2014). Prefrontal cortical GABA transmission modulates discrimination and latent inhibition of conditioned fear: relevance for schizophrenia. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 39, 2473–2484.Google Scholar
Reis Marques, T, Taylor, H, Chaddock, C, Dell'Acqua, F, Handley, R, Reinders, AA, Mondelli, V, Bonaccorso, S, Diforti, M, Simmons, A, David, AS, Murray, RM, Pariante, CM, Kapur, S, Dazzan, P (2014). White matter integrity as a predictor of response to treatment in first episode psychosis. Brain: a Journal of Neurology 137, 172–182.Google Scholar
Rubinov, M, Sporns, O (2010). Complex network measures of brain connectivity: uses and interpretations. NeuroImage 52, 1059–1069.Google Scholar
Sambataro, F, Blasi, G, Fazio, L, Caforio, G, Taurisano, P, Romano, R, Di Giorgio, A, Gelao, B, Lo Bianco, L, Papazacharias, A, Popolizio, T, Nardini, M, Bertolino, A (2010). Treatment with olanzapine is associated with modulation of the default mode network in patients with schizophrenia. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 35, 904–912.Google Scholar
Shi, F, Yap, PT, Gao, W, Lin, W, Gilmore, JH, Shen, D (2012). Altered structural connectivity in neonates at genetic risk for schizophrenia: a combined study using morphological and white matter networks. NeuroImage 62, 1622–1633.Google Scholar
Skudlarski, P, Schretlen, DJ, Thaker, GK, Stevens, MC, Keshavan, MS, Sweeney, JA, Tamminga, CA, Clementz, BA, O'Neil, K, Pearlson, GD (2013). Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives. American Journal of Psychiatry 170, 886–898.Google Scholar
Snitz, BE, MacDonald, A 3rd, Cohen, JD, Cho, RY, Becker, T, Carter, CS (2005). Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment. American Journal of Psychiatry 162, 2322–2329.Google Scholar
Sporns, O, Tononi, G, Kotter, R (2005). The human connectome: a structural description of the human brain. PLoS Computational Biology 1, e42.Google Scholar
Stephan, KE, Friston, KJ, Frith, CD (2009). Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophrenia Bulletin 35, 509–527.Google Scholar
Storey, JD (2002). A direct approach to false discovery rates. Journal of the Royal Statistical Society: Series B (Statistical Methodology) 64, 479–498.Google Scholar
Szeszko, PR, Robinson, DG, Ikuta, T, Peters, BD, Gallego, JA, Kane, J, Malhotra, AK (2014). White matter changes associated with antipsychotic treatment in first-episode psychosis. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 39, 1324–1331.Google Scholar
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273–289.Google Scholar
Van den Heuvel, MP, Mandl, RC, Stam, CJ, Kahn, RS, Hulshoff Pol, HE (2010). Aberrant frontal and temporal complex network structure in schizophrenia: a graph theoretical analysis. Journal of Neuroscience: the Official Journal of the Society for Neuroscience 30, 15915–15926.CrossRefGoogle ScholarPubMed
Van den Heuvel, MP, Sporns, O, Collin, G, Scheewe, T, Mandl, RC, Cahn, W, Goni, J, Hulshoff Pol, HE, Kahn, RS (2013). Abnormal rich club organization and functional brain dynamics in schizophrenia. JAMA Psychiatry 70, 783–792.Google Scholar
Van Veelen, NM, Vink, M, Ramsey, NF, van Buuren, M, Hoogendam, JM, Kahn, RS (2011). Prefrontal lobe dysfunction predicts treatment response in medication-naive first-episode schizophrenia. Schizophrenia Research 129, 156–162.Google Scholar
Wang, Q, Cheung, C, Deng, W, Li, M, Huang, C, Ma, X, Wang, Y, Jiang, L, Sham, PC, Collier, DA, Gong, Q, Chua, SE, McAlonan, GM, Li, T (2013). White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment. Psychological Medicine 43, 2301–2309.Google Scholar
Wang, Q, Su, TP, Zhou, Y, Chou, KH, Chen, IY, Jiang, T, Lin, CP (2012). Anatomical insights into disrupted small-world networks in schizophrenia. NeuroImage 59, 1085–1093.Google Scholar
Watts, DJ, Strogatz, SH (1998). Collective dynamics of ‘small-world’ networks. Nature 393, 440–442.CrossRefGoogle ScholarPubMed
Wernicke, C (1906). Grundrisse der Psychiatrie (Plans of Psychiatry). Thieme: Leipzig, Germany.Google Scholar
Zalesky, A, Fornito, A, Seal, ML, Cocchi, L, Westin, CF, Bullmore, ET, Egan, GF, Pantelis, C (2011). Disrupted axonal fiber connectivity in schizophrenia. Biological Psychiatry 69, 80–89.Google Scholar
Zhang, Z, Liao, W, Chen, H, Mantini, D, Ding, J-R, Xu, Q, Wang, Z, Yuan, C, Chen, G, Jiao, Q (2011). Altered functional–structural coupling of large-scale brain networks in idiopathic generalized epilepsy. Brain 134, 2912–2928.Google Scholar
Zong, X, Hu, M, Li, Z, Cao, H, He, Y, Liao, Y, Zhou, J, Sang, D, Zhao, H, Tang, J, Lv, L, Chen, X (2015). N-acetylaspartate reduction in the medial prefrontal cortex following 8 weeks of risperidone treatment in first-episode drug-naive schizophrenia patients. Scientific Reports 5, 9109.Google Scholar
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