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Peripheral inflammatory markers associated with brain volume reduction in patients with bipolar I disorder

Published online by Cambridge University Press:  20 December 2021

Shang-Ying Tsai Open the ORCID record for Shang-Ying Tsai [Opens in a new window] ,
Martha Sajatovic ,
Jung-Lung Hsu ,
Kuo-Hsuan Chung ,
Pao-Huan Chen  and
Yu-Jui Huang
Shang-Ying Tsai*
Affiliation:
Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Martha Sajatovic
Affiliation:
Department of Psychiatry, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Jung-Lung Hsu
Affiliation:
Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan Graduate Institute of Humanities in Medicine and Research Center for Brain and Consciousness, College of Humanities And Social Sciences, Taipei Medical University, Taipei, Taiwan
Kuo-Hsuan Chung
Affiliation:
Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Pao-Huan Chen
Affiliation:
Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Yu-Jui Huang
Affiliation:
Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
*
Author for correspondence: Shang-Ying Tsai, Email: tmcpsyts@tmu.edu.tw
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Abstract

Background:

Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients.

Methods:

Euthymic patients with bipolar I disorder (BD-I) aged 20–45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), chitinase-3-like protein 1 (also known as YKL-40), fractalkine (FKN), soluble tumour necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others.

Results:

We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus, and supramarginal gyrus. A greater number of total lifetime mood episodes were also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes.

Conclusions:

The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.

Keywords

Chemokinechitinase-3-like protein 1YKL-40sTNF-R1brain volumebipolar I disorder
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 34 , Issue 4 , August 2022 , pp. 191 - 200
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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References

Altamura, AC, Maggioni, E, Dhanoa, T, Ciappolino, V, Paoli, RA, Cremaschi, L, Prunas, C, Orsenigo, G, Caletti, E, Cinnante, CM, Triulzi, FM, Dell’Osso, B, Yatham, L and Brambilla, P (2018) The impact of psychosis on brain anatomy in bipolar disorder: a structural MRI study. Journal of Affective Disorders 233, 100–109.CrossRefGoogle ScholarPubMed
Ascoli, BM, Géa, LP, Colombo, R, Barbé-Tuana, FM, Kapczinski, F and Rosa, AR (2016) The role of macrophage polarization on bipolar disorder: identifying new therapeutic targets. The Australian and New Zealand Journal of Psychiatry 50, 618–630.CrossRefGoogle ScholarPubMed
Bélanger, M and Magistretti, PJ (2009) The role of astroglia in neuroprotection. Dialogues in Clinical Neuroscience 11, 281–295.CrossRefGoogle ScholarPubMed
Bonneh-Barkay, D, Bissel, SJ, Kofler, J, Starkey, A, Wang, G and Wiley, CA (2012) Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. Brain Pathology 22, 530–546.CrossRefGoogle ScholarPubMed
Bonneh-Barkay, D, Wang, G, Starkey, A, Hamilton, RL and Wiley, CA (2010) In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. Journal of Neuroinflammation 7, 34.CrossRefGoogle ScholarPubMed
da Fonseca, AC, Matias, D, Garcia, C, Amaral, R, Geraldo, LH, Freitas, C and Lima, FR (2014) The impact of microglial activation on blood-brain barrier in brain diseases. Frontiers in Cellular Neuroscience 8: 362.CrossRefGoogle ScholarPubMed
Dieset, I, Mørch, RH, Hope, S, Hoseth, EZ, Reponen, EJ, Gran, JM, Aas, M, Michelsen, AE, Reichborn-Kjennerud, T, Nesvåg, R, Agartz, I, Melle, I, Aukrust, P, Djurovic, S, Ueland, T and Andreassen, OA (2019) An association between YKL-40 and type 2 diabetes in psychotic disorders. Acta Psychiatrica Scandinavica 139, 37–45.CrossRefGoogle ScholarPubMed
Dietsche, B, Kircher, T and Falkenberg, I (2017) Structural brain changes in schizophrenia at different stages of the illness: a selective review of longitudinal magnetic resonance imaging studies. The Australian and New Zealand Journal of Psychiatry 51, 500–508.CrossRefGoogle ScholarPubMed
Doganavsargil-Baysal, O, Cinemre, B, Aksoy, UM, Akbas, H, Metin, O, Fettahoglu, C, Gokmen, Z and Davran, F (2013) Levels of TNF-α, soluble TNF receptors (sTNFR1, sTNFR2), and cognition in bipolar disorder. Human Psychopharmacology 28, 160–167.CrossRefGoogle Scholar
Fakhoury, M (2018) Microglia and astrocytes in Alzheimer’s disease: implications for therapy. Current Neuropharmacology 16, 508–518.CrossRefGoogle ScholarPubMed
Falcon, C, Monté-Rubio, GC, Grau-Rivera, O, Suárez-Calvet, M, Sánchez-Valle, R, Rami, L, Bosch, B, Haass, C, Gispert, JD and Molinuevo, JL(2019). CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals. NeuroImage Clinical 23, 101801.CrossRefGoogle ScholarPubMed
Goldsmith, DR, Rapaport, MH and Miller, BJ (2016) A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Molecular Psychiatry 21, 1696–1709.CrossRefGoogle ScholarPubMed
Hallahan, B, Newell, J, Soares, JC, Brambilla, P, Strakowski, SM, Fleck, DE, Kieseppä, T, Altshuler, LL, Fornito, A, Malhi, GS, McIntosh, AM, Yurgelun-Todd, DA, Labar, KS, Sharma, V, MacQueen, GM, Murray, RM and McDonald, C (2011) Structural magnetic resonance imaging in bipolar disorder: an international collaborative mega-analysis of individual adult patient data. Biological Psychiatry 69, 326–335.CrossRefGoogle ScholarPubMed
Hamilton, M (1967) Development of a rating scale for primary depressive illness. The British Journal of Social and Clinical Psychology 6, 278–296.CrossRefGoogle ScholarPubMed
Hanford, LC, Nazarov, A, Hall, GB and Sassi, RB (2016) Cortical thickness in bipolar disorder: a systematic review. Bipolar Disorders 18, 4–18.CrossRefGoogle ScholarPubMed
Hewett, SJ, Jackman, NA and Claycomb, RJ (2012) Interleukin-1β in central nervous system injury and repair. European Journal of Neurodegenerative Disease 1, 195–211.Google ScholarPubMed
Hibar, DP, Westlye, LT and Doan, NT (2018) Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA bipolar disorder working group. Molecular Psychiatry 23, 932–942.CrossRefGoogle ScholarPubMed
Hope, S, Dieset, I, Agartz, I, Steen, NE, Ueland, T, Melle, I, Aukrust, P and Andreassen, OA (2011) Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia. Journal of Psychiatric Research 45, 1608–1616.CrossRefGoogle Scholar
Hoseth, EZ, Ueland, T, Dieset, I, Birnbaum, R, Shin, JH, Kleinman, JE, Hyde, TM, Mørch, RH, Hope, S, Lekva, T, Abraityte, AJ, Michelsen, AE, Melle, I, Westlye, LT, Ueland, T, Djurovic, S, Aukrust, P, Weinberger, DR and Andreassen, OA (2017) A study of TNF pathway activation in schizophrenia and bipolar disorder in plasma and brain tissue. Schizophrenia Bulletin 43, 881–890.Google ScholarPubMed
Isgren, A, Sellgren, C, Ekman, CJ, Holmén-Larsson, J, Blennow, K, Zetterberg, H, Jakobsson, J and Landén, M (2017) Markers of neuroinflammation and neuronal injury in bipolar disorder: relation to prospective clinical outcomes. Brain, Behavior, and Immunity 65, 195–201.CrossRefGoogle ScholarPubMed
Jakobsson, J, Bjerke, M, Sahebi, S, Isgren, A, Ekman, CJ, Sellgren, C, Olsson, B, Zetterberg, H, Blennow, K, Palsson, E and Landén, M (2015) Monocyte and microglial activation in patients with mood-stabilized bipolar disorder. Journal of Psychiatry & Neuroscience 40, 250–258.CrossRefGoogle ScholarPubMed
Johansen, JS, Lottenburger, T, Nielsen, HJ, Jensen, JE, Svendsen, MN, Kollerup, G and Christensen, IJ (2008) Diurnal, weekly, and long-time variation in serum concentrations of YKL-40 in healthy subjects. Cancer Epidemiology, Biomarkers & Prevention 17, 2603–2608.CrossRefGoogle ScholarPubMed
Kastrup, J (2012) Can YKL-40 be a new inflammatory biomarker in cardiovascular disease? Immunobiology 217, 483–491.CrossRefGoogle ScholarPubMed
Keohane, A, Ryan, S, Maloney, E, Sullivan, AM and Nolan, YM (2010) Tumour necrosis factor-alpha impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: role of Hes1. Molecular and Cellular Neuroscience 43, 127–135.CrossRefGoogle Scholar
Kim, YK, Myint, AM, Lee, BH, Han, CS, Lee, SW, Leonard, BE and Steinbusch, HW (2004) T-helper types 1, 2, and 3 cytokine interactions in symptomatic manic patients. Psychiatry Research 129, 267–272.CrossRefGoogle ScholarPubMed
Kjaergaard, AD, Bojesen, SE, Johansen, JS and Nordestgaard, BG (2010) Elevated plasma YKL-40 levels and ischemic stroke in the general population. Annals of Neurology 68, 672–680.CrossRefGoogle ScholarPubMed
Majewski, S, Tworek, D, Szewczyk, K, Kiszałkiewicz, J, Kurmanowska, Z, Brzeziańska-Lasota, E, Jerczyńska, H, Antczak, A, Piotrowski, WJ and Górski, P (2019) Overexpression of chitotriosidase and YKL-40 in peripheral blood and sputum of healthy smokers and patients with chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease 14, 1611–1631.CrossRefGoogle ScholarPubMed
Milenkovic, VM, Stanton, EH, Nothdurfter, C, Rupprecht, R and Wetzel, CH (2019) The role of chemokines in the pathophysiology of major depressive disorder. International Journal of Molecular Sciences 20, 2283.CrossRefGoogle ScholarPubMed
Mørch, RH, Dieset, I, Færden, A, Reponen, EJ, Hope, S, Hoseth, EZ, Gardsjord, ES, Aas, M, Iversen, T, Joa, I, Morken, G, Agartz, I, Melle, I, Aukrust, P, Djurovic, S and Ueland, T and Andreassen, OA (2019) Inflammatory markers are altered in severe mental disorders independent of comorbid cardiometabolic disease risk factors. Psycholgical Medicine 49, 1749–1757.CrossRefGoogle ScholarPubMed
Orhan, F, Schwieler, L, Fatouros-Bergman, H, Malmqvist, A, Cervenka, S, Collste, K, Flyckt, L, Farde, L, Sellgren, CM, Piehl, F, Karolinska Schizophrenia Project (KaSP) Consortium, Engberg G and Erhardt S (2018) Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis. Acta Psychiatrica Scandinavica 138, 432–440.CrossRefGoogle ScholarPubMed
Pan, WH (2019, July 12). Nutrition and health survey in Taiwan 2013–2016. Retrieved from https://hpa.gov.tw/Cms/File/Attach/6201/File_12811.pdf.Google Scholar
Patel, JP and Frey, BN (2015) Disruption in the blood-brain barrier: the missing link between brain and body inflammation in bipolar disorder? Neural Plasticity 2015, 708306.CrossRefGoogle ScholarPubMed
Phillips, ML and Swartz, HA (2014) A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research. The American Journal of Psychiatry 171, 829–843.CrossRefGoogle Scholar
Pinto, JV, Passos, IC, Librenza-Garcia, D, Marcon, G, Schneider, MA, Conte, JH, da Silva, J, Lima, LP, Quincozes-Santos, A, Kauer-Sant, AM and Kapczinski, F (2018) Neuron-glia interaction as a possible pathophysiological mechanism of bipolar disorder. Current Neuropharmacology 16, 519–532.CrossRefGoogle ScholarPubMed
Rao, JS, Harry, G J, Rapoport, SI and Kim, HW (2010) Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Molecular Psychiatry 15, 384–392.CrossRefGoogle ScholarPubMed
Rathcke, CN and Vestergaard, H (2009) YKL-40--an emerging biomarker in cardiovascular disease and diabetes. Cardiovascular Diabetology 8, 61.CrossRefGoogle Scholar
Réus, GZ, Fries, GR, Stertz, L, Badawy, M, Passos, IC, Barichello, T, Kapczinski, F and Quevedo, J (2015) The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience 300, 141–154.CrossRefGoogle Scholar
Rolstad, S, Jakobsson, J, Sellgren, C, Isgren, A, Ekman, CJ, Bjerke, M, Blennow, K, Zetterberg, H, Pålsson, E and Landén, M (2015) CSF neuroinflammatory biomarkers in bipolar disorder are associated with cognitive impairment. European Neuropsychopharmacology 25, 1091–1098.CrossRefGoogle ScholarPubMed
Sahin, B, Inanli, I, Calıskan, AM and Uysal, S (2019) Chitinase-3-like protein 1 levels in bipolar disorder. Saudi Medical Journal 40, 26–32.CrossRefGoogle ScholarPubMed
Selvaraj, S, Arnone, D, Job, D, Stanfield, A, Farrow, TF, Nugent, AC, Scherk, H, Gruber, O, Chen, X, Sachdev, PS, Dickstein, DP, Malhi, GS, Ha, TH, Ha, K, Phillips, ML and McIntosh, AM (2012) Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies. Bipolar Disorders 14, 135–145.CrossRefGoogle ScholarPubMed
Söderlund, J, Olsson, SK, Samuelsson, M, Walther-Jallow, L, Johansson, C, Erhardt, S, Landén, M and Engberg, G (2011) Elevation of cerebrospinal fluid interleukin-1ß in bipolar disorder. Journal of Psychiatry & Neuroscience 36, 114–118.CrossRefGoogle ScholarPubMed
Steiner, J, Bielau, H, Brisch, R, Danos, P, Ullrich, O, Mawrin, C, Bernstein, HG and Bogerts, B (2008) Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. Journal of Psychiatric Research 42, 151–157.CrossRefGoogle ScholarPubMed
Strakowski, SM, DelBello, MP, Fleck, DE, Adler, CM, Anthenelli, RM, Keck, PE Jr, Arnold, LM and Amicone, J (2005) Effects of co-occurring alcohol abuse on the course of bipolar disorder following a first hospitalization for mania. Archieve of General Psychiatry 62, 851–858.CrossRefGoogle ScholarPubMed
Stuart, MJ and Baune, BT (2014). Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies. Neuroscience and Biobehavioral Reviews 42, 93–115.CrossRefGoogle ScholarPubMed
Szepesi, Z, Manouchehrian, O, Bachiller, S and Deierborg, T (2018) Bidirectional microglia-neuron communication in health and disease. Frontiers In Cellular Neuroscience 12, 323.CrossRefGoogle ScholarPubMed
Tsai, SY, Gildengers, AG, Hsu, JL, Chung, KH, Chen, PH and Huang, YJ (2019) Inflammation associated with volume reduction in the gray matter and hippocampus of older patients with bipolar disorder. Journal of Affective Disorders 244, 60–66.CrossRefGoogle ScholarPubMed
Tsai, SY, Sajatovic, M, Hsu, JL, Chung, KH, Chen, PH and Huang, YJ (2020) Body mass index, residual psychotic symptoms, and inflammation associated with brain volume reduction in older patients with schizophrenia. International Journal of Geriatric Psychiatry 35, 728–736.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B and 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.CrossRefGoogle ScholarPubMed
Uranova, NA, Vostrikov, VM, Orlovskaya, DD and Rachmanova, VI (2004) Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley neuropathology consortium. Schizophrenia Research 67, 269–275.CrossRefGoogle ScholarPubMed
Wang, TY, Lee, SY, Chen, SL, Chang, YH, Wang, LJ, Chen, PS, Chen, SH, Chu, CH, Huang, SY, Tzeng, NS, Li, C L, Chung, YL, Hsieh, TH, Lee, IH, Chen, KC, Yang, YK, Hong, JS and Lu, RB (2016) Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder. Scientific Reports 6, 27431.CrossRefGoogle ScholarPubMed
Yajima, N, Kasama, T, Isozaki, T, Odai, T, Matsunawa, M, Negishi, M, Ide, H, Kameoka, Y, Hirohata, S and Adachi, M (2005) Elevated levels of soluble fractalkine in active systemic lupus erythematosus: potential involvement in neuropsychiatric manifestations. Arthritis and Rheumatism 52, 1670–1675.CrossRefGoogle ScholarPubMed
Young, RC, Biggs, JT, Ziegler, VE and Meyer, DA (1978) A rating scale for mania: reliability, validity and sensitivity. The British Journal of Psychiatry 133, 429–435.CrossRefGoogle ScholarPubMed
Zhang, R, Song, J, Isgren, A, Jakobsson, J, Blennow, K, Sellgren, CM, Zetterberg, H, Bergen, SE and Landén, M (2020) Genome-wide study of immune biomarkers in cerebrospinal fluid and serum from patients with bipolar disorder and controls. Translational Psychiatry 10, 58.CrossRefGoogle ScholarPubMed