Abstract
Background
Previous studies have reported that galectin-3 is involved in inflammatory processes in the central nervous system and that neuroinflammation may play a role in the pathogenesis of schizophrenia. However, the link between schizophrenia and various galectins is unclear.
Objective
The objective of the present study is to determine whether galectin, a well-known lectin protein that binds to μ-galactoside, is associated with chronic schizophrenia.
Methods
Thirty-six patients with schizophrenia and 36 healthy controls participated in this study. Schizophrenia symptoms were assessed using the Brief Psychiatry Rating Scale (BPRS). Serum galectin-1 and galectin-3 levels were evaluated using ELISA and compared between the participant groups. Correlation analyses were also performed to examine the relationship between BPRS scores and each galectin level.
Results
Serum galectin-3 levels were significantly higher in patients with schizophrenia than they were in controls (p = 0.009, d = 0.640); however, serum galectin-1 levels were not significantly different between the groups (p = 0.513). No significant correlation was identified between serum galectin-3 level and the total BPRS score; however, a significant positive correlation was found between the serum galectin-3 level and the positive symptom score of the BPRS (ρ = 0.355; p = 0.033). Additionally, a significant negative correlation was identified between serum galectin-3 levels and the negative symptom score of the BPRS (ρ = −0.387; p = 0.020).
Conclusions
Given the high serum levels of galectin-3 found in patients with schizophrenia compared with that in controls, these findings may support the inflammation hypothesis of schizophrenia.
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References
Alves CM, Silva DA, Azzolini AE, Marzocchi-Machado CM, Carvalho JV, Pajuaba AC, Lucisano-Valim YM, Chammas R, Liu FT, Roque-Barreira MC, Mineo JR (2010) Galectin-3 plays a modulatory role in the life span and activation of murine neutrophils during early Toxoplasma gondii infection. Immunobiology 215:475–485
Andreasen NC (1991) Assessment issues and the cost of schizophrenia. Schizophr Bull 17:475–481
Arai M, Yuzawa H, Nohara I, Ohnishi T, Obata N, Iwayama Y, Haga S, Toyota T, Ujike H, Arai M, Ichikawa T, Nishida A, Tanaka Y, Furukawa A, Aikawa Y, Kuroda O, Niizato K, Izawa R, Nakamura K, Mori N, Matsuzawa D, Hashimoto K, Iyo M, Sora I, Matsushita M, Okazaki Y, Yoshikawa T, Miyata T, Itokawa M (2010) Enhanced carbonyl stress in a subpopulation of schizophrenia. Arch Gen Psychiatry 67:589–597
Barondes SH, Cooper DN, Gitt MA, Leffler H (1994) Galectins. Structure and function of a large family of animal lectins. J Biol Chem 269:20807–20810
Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR, Bloomfield MA, Bonoldi I, Kalk N, Turkheimer F, McGuire P, de Paola V, Howes OD (2016) Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [(11)C]PBR28 PET brain imaging study. Am J Psychiatry 173:44–52
Brewer CF (2004) Thermodynamic binding studies of galectin-1, -3 and -7. Glycoconj J 19:459–465
Brook S, Walden J, Benattia I, Siu CO, Romano SJ (2005) Ziprasidone and haloperidol in the treatment of acute exacerbation of schizophrenia and schizoaffective disorder: comparison of intramuscular and oral formulations in a 6-week, randomized, blinded-assessment study. Psychopharmacology 178:514–523
Burguillos MA, Svensson M, Schulte T, Boza-Serrano A, Garcia-Quintanilla A, Kavanagh E, Santiago M, Viceconte N, Oliva-Martin MJ, Osman AM, Salomonsson E, Amar L, Persson A, Blomgren K, Achour A, Englund E, Leffler H, Venero JL, Joseph B, Deierborg T (2015) Microglia-secreted galectin-3 acts as a toll-like receptor 4 ligand and contributes to microglial activation. Cell Rep
Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD (2016) Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology 233:1637–1650
Chen C, Duckworth CA, Zhao Q, Pritchard DM, Rhodes JM, Yu LG (2013) Increased circulation of galectin-3 in cancer induces secretion of metastasis-promoting cytokines from blood vascular endothelium. Clin Cancer Res 19:1693–1704
Chen SS, Sun LW, Brickner H, Sun PQ (2015) Downregulating galectin-3 inhibits proinflammatory cytokine production by human monocyte-derived dendritic cells via RNA interference. Cell Immunol 294:44–53
Davalieva K, Maleva Kostovska I, Dwork AJ (2016) Proteomics research in schizophrenia. Front Cell Neurosci 10:18
de Oliveira FL, Gatto M, Bassi N, Luisetto R, Ghirardello A, Punzi L, Doria A (2015) Galectin-3 in autoimmunity and autoimmune diseases. Exp Biol Med (Maywood) 240:1019–1028
de Waard A, Hickman S, Kornfeld S (1976) Isolation and properties of beta-galactoside binding lectins of calf heart and lung. J Biol Chem 251:7581–7587
Desmedt V, Desmedt S, Delanghe JR, Speeckaert R, Speeckaert MM (2016) Galectin-3 in renal pathology: more than just an innocent bystander. Am J Nephrol 43:305–317
Dimitrov DH, Lee S, Yantis J, Valdez C, Paredes RM, Braida N, Velligan D, Walss-Bass C (2013) Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: potential role for IL-17 pathway. Schizophr Res 151:29–35
Dumic J, Dabelic S, Flogel M (2006) Galectin-3: an open-ended story. Biochim Biophys Acta 1760:616–635
Elola MT, Wolfenstein-Todel C, Troncoso MF, Vasta GR, Rabinovich GA (2007) Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival. Cell Mol Life Sci 64:1679–1700
Fan X, Liu EY, Freudenreich O, Park JH, Liu D, Wang J, Yi Z, Goff D, Henderson DC (2010) Higher white blood cell counts are associated with an increased risk for metabolic syndrome and more severe psychopathology in non-diabetic patients with schizophrenia. Schizophr Res 118:211–217
Fryk E, Sundelin JP, Strindberg L, Pereira MJ, Federici M, Marx N, Nystrom FH, Schmelz M, Svensson PA, Eriksson JW, Boren J, Jansson PA (2016) Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients. Metabolism 65:998–1006
Hrynchyshyn N, Jourdain P, Desnos M, Diebold B, Funck F (2013) Galectin-3: a new biomarker for the diagnosis, analysis and prognosis of acute and chronic heart failure. Arch Cardiovasc Dis 106:541–546
Iacobini C, Menini S, Oddi G, Ricci C, Amadio L, Pricci F, Olivieri A, Sorcini M, Di Mario U, Pesce C, Pugliese G (2004) Galectin-3/AGE-receptor 3 knockout mice show accelerated AGE-induced glomerular injury: evidence for a protective role of galectin-3 as an AGE receptor. FASEB J 18:1773–1775
Issa SF, Christensen AF, Lottenburger T, Junker K, Lindegaard H, Horslev-Petersen K, Junker P (2015) Within-day variation and influence of physical exercise on circulating galectin-3 in patients with rheumatoid arthritis and healthy individuals. Scand J Immunol 82:70–75
Iwamoto M, Taguchi C, Sasaguri K, Kubo KY, Horie H, Yamamoto T, Onozuka M, Sato S, Kadoya T (2010) The galectin-1 level in serum as a novel marker for stress. Glycoconj J 27:419–425
Kajitani K, Kobayakawa Y, Nomaru H, Kadoya T, Horie H, Nakabeppu Y (2014) Characterization of galectin-1-positive cells in the mouse hippocampus. Neuroreport 25:171–176
Kajitani K, Nomaru H, Ifuku M, Yutsudo N, Dan Y, Miura T, Tsuchimoto D, Sakumi K, Kadoya T, Horie H, Poirier F, Noda M, Nakabeppu Y (2009) Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult mouse hippocampus. Cell Death Differ 16:417–427
Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB (2015) Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry 2:258–270
Khandaker GM, Dantzer R (2016) Is there a role for immune-to-brain communication in schizophrenia? Psychopharmacology 233:1559–1573
Kim YK, Kim L, Lee MS (2000) Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res 44:165–175
Koike S, Kayama T, Arai M, Horiuchi Y, Kobori A, Miyashita M, Itokawa M, Ogasawara Y (2015) Characterization of modified proteins in plasma from a subtype of schizophrenia based on carbonyl stress: protein carbonyl is a possible biomarker of psychiatric disorders. Biochem Biophys Res Commun 467:361–366
Kouidrat Y, Amad A, Arai M, Miyashita M, Lalau JD, Loas G, Itokawa M (2015) Advanced glycation end products and schizophrenia: a systematic review. J Psychiatr Res 66-67:112–117
Krzeslak A, Lipinska A (2004) Galectin-3 as a multifunctional protein. Cell Mol Biol Lett 9:305–328
Lai CY, Scarr E, Udawela M, Everall I, Chen WJ, Dean B (2016) Biomarkers in schizophrenia: a focus on blood based diagnostics and theranostics. World J Psychiatry 6:102–117
Leboyer M, Oliveira J, Tamouza R, Groc L (2016) Is it time for immunopsychiatry in psychotic disorders? Psychopharmacology 233:1651–1660
Lee KU, Jeon YW, Lee HK, Jun TY (2009) Efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia. Hum Psychopharmacol 24:447–452
Levi G, Teichberg VI (1984) The distribution of electrolectin in mouse: genetic and ontogenic variations. Biochem Biophys Res Commun 119:801–806
Liu FT, Rabinovich GA (2005) Galectins as modulators of tumour progression. Nat Rev Cancer 5:29–41
Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B (2011) Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 70:663–671
Monji A, Kato T, Kanba S (2009) Cytokines and schizophrenia: microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci 63:257–265
Mueser KT, McGurk SR (2004) Schizophrenia. Lancet 363:2063–2072
Nakahara S, Raz A (2006) On the role of galectins in signal transduction. Methods Enzymol 417:273–289
Nangia-Makker P, Honjo Y, Sarvis R, Akahani S, Hogan V, Pienta KJ, Raz A (2000) Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am J Pathol 156:899–909
Nasef NA, Mehta S, Ferguson LR (2017) Susceptibility to chronic inflammation: an update. Arch Toxicol 91:1131–1141
Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G (2002) Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry 59:337–345
Ouyang J, Plutschow A, Pogge von Strandmann E, Reiners KS, Ponader S, Rabinovich GA, Neuberg D, Engert A, Shipp MA (2013) Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma. Blood 121:3431–3433
Overall JE, Gorham DR (1988) The Brief Psychiatric Rating Scale (BPRS): recent developments in ascertainment and scaling. Psychopharmacol Bull 24:97–99
Shafer A (2005) Meta-analysis of the brief psychiatric rating scale factor structure. Psychol Assess 17:324–335
Sirko S, Irmler M, Gascon S, Bek S, Schneider S, Dimou L, Obermann J, De Souza PD, Poirier F, Beckers J, Hauck SM, Barde YA, Gotz M (2015) Astrocyte reactivity after brain injury-: the role of galectins 1 and 3. Glia 63:2340–2361
Smit AJ, Lutgers HL (2004) The clinical relevance of advanced glycation endproducts (AGE) and recent developments in pharmaceutics to reduce AGE accumulation. Curr Med Chem 11:2767–2784
Stanta JL, Saldova R, Struwe WB, Byrne JC, Leweke FM, Rothermund M, Rahmoune H, Levin Y, Guest PC, Bahn S, Rudd PM (2010) Identification of N-glycosylation changes in the CSF and serum in patients with schizophrenia. J Proteome Res 9:4476–4489
Telford JE, Bones J, McManus C, Saldova R, Manning G, Doherty M, Leweke FM, Rothermundt M, Guest PC, Rahmoune H, Bahn S, Rudd PM (2012) Antipsychotic treatment of acute paranoid schizophrenia patients with olanzapine results in altered glycosylation of serum glycoproteins. J Proteome Res 11:3743–3752
Tomasik J, Schwarz E, Guest PC, Bahn S (2012) Blood test for schizophrenia. Eur Arch Psychiatry Clin Neurosci 262(Suppl 2):S79–S83
Tourjman V, Kouassi E, Koue ME, Rocchetti M, Fortin-Fournier S, Fusar-Poli P, Potvin S (2013) Antipsychotics’ effects on blood levels of cytokines in schizophrenia: a meta-analysis. Schizophr Res 151:43–47
Trepanier MO, Hopperton KE, Mizrahi R, Mechawar N, Bazinet RP (2016) Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review. Mol Psychiatry 21:1009–1026
Tunca Z, Kivircik Akdede B, Ozerdem A, Alkin T, Polat S, Ceylan D, Bayin M, Cengizcetin Kocuk N, Simsek S, Resmi H, Akan P (2015) Diverse glial cell line-derived neurotrophic factor (GDNF) support between mania and schizophrenia: a comparative study in four major psychiatric disorders. Eur Psychiatry 30:198–204
Tynan RJ, Beynon SB, Hinwood M, Johnson SJ, Nilsson M, Woods JJ, Walker FR (2013) Chronic stress-induced disruption of the astrocyte network is driven by structural atrophy and not loss of astrocytes. Acta Neuropathol 126:75–91
van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS (2008) Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry 64:820–822
Verschuere T, Van Woensel M, Fieuws S, Lefranc F, Mathieu V, Kiss R, Van Gool SW, De Vleeschouwer S (2013) Altered galectin-1 serum levels in patients diagnosed with high-grade glioma. J Neuro-Oncol 115:9–17
Walker AR, Bonomi R, Popov V, Gelovani JG, Andres Cisneros G (2017) Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies. J Mol Graph Model 71:211–217
Weiner E, Conley RR, Ball MP, Feldman S, Gold JM, Kelly DL, Wonodi I, McMahon RP, Buchanan RW (2010) Adjunctive risperidone for partially responsive people with schizophrenia treated with clozapine. Neuropsychopharmacology 35:2274–2283
Xiu MH, Yang GG, Tan YL, Chen DC, Tan SP, Wang ZR, Yang FD, Okusaga O, Soares JC, Zhang XY (2014) Decreased interleukin-10 serum levels in first-episode drug-naive schizophrenia: relationship to psychopathology. Schizophr Res 156:9–14
Yilmaz H, Cakmak M, Inan O, Darcin T, Akcay A (2015) Increased levels of galectin-3 were associated with prediabetes and diabetes: new risk factor? J Endocrinol Investig 38:527–533
Acknowledgments
The authors thank all of the staff in the affiliated hospitals of Kyushu University (Hakomatsu Hospital, Kawazoe Hospital, and Imajuku Hospital) for recruiting the participants.
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This study was approved by the Ethics Committee of the Faculty of Arts and Science, Kyushu University, Japan. Informed written consent was obtained from each participant after they were given information about the study.
Funding
This study was funded by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Japan Society for the Promotion of Science (25870494 to K. Kajitani).
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The authors declare that they have no conflicts of interest.
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Kajitani, K., Yanagimoto, K. & Nakabeppu, Y. Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia: implications for the role of inflammation. Psychopharmacology 234, 2919–2927 (2017). https://doi.org/10.1007/s00213-017-4683-9
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DOI: https://doi.org/10.1007/s00213-017-4683-9