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Brain free water alterations in first-episode psychosis: a longitudinal analysis of diagnosis, course of illness, and medication effects

Published online by Cambridge University Press:  08 January 2020

J. Y. Guo Open the ORCID record for J. Y. Guo [Opens in a new window] ,
T. A. Lesh ,
T. A. Niendam ,
J. D. Ragland ,
L. M. Tully  and
C. S. Carter
J. Y. Guo
Affiliation:
Imaging Research Center, the University of California at Davis, Sacramento, CA, USA Center for Neuroscience, the University of California at Davis, Davis, CA, USA
T. A. Lesh
Affiliation:
Imaging Research Center, the University of California at Davis, Sacramento, CA, USA Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA
T. A. Niendam
Affiliation:
Imaging Research Center, the University of California at Davis, Sacramento, CA, USA Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA
J. D. Ragland
Affiliation:
Imaging Research Center, the University of California at Davis, Sacramento, CA, USA Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA
L. M. Tully
Affiliation:
Imaging Research Center, the University of California at Davis, Sacramento, CA, USA Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA
C. S. Carter*
Affiliation:
Imaging Research Center, the University of California at Davis, Sacramento, CA, USA Center for Neuroscience, the University of California at Davis, Davis, CA, USA Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA
*
Author for correspondence: C. S. Carter, E-mail: cscarter@ucdavis.edu
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Abstract

Background

Multiple lines of evidence suggest the presence of altered neuroimmune processes in patients with schizophrenia (Sz) and severe mood disorders. Recent studies using a novel free water diffusion tensor imaging (FW DTI) approach, proposed as a putative biomarker of neuroinflammation, atrophy, or edema, have shown significantly increased FW in patients with Sz. However no studies to date have investigated the longitudinal stability of FW alterations during the early course of psychosis, nor have studies focused separately on FE psychosis patients with Sz or bipolar disorder (BD) with psychotic features.

Methods

The current study included 188 participants who underwent diffusion magnetic resonance imaging scanning at baseline. Sixty-four participants underwent follow-up rescanning after 12 months. DTI-based alterations in patients were calculated using voxelwise tract-based spatial statistics and region of interest analyses.

Results

Patients with FE psychosis, both Sz and BD, exhibited increased FW at illness onset which remained unchanged over the 12-month follow-up period. Preliminary analyses suggested that antipsychotic medication exposure was associated with higher FW in gray matter that reached significance in the BD group. Higher FW in white matter correlated with negative symptom severity.

Conclusions

Our results support the presence of elevated FW at the onset of psychosis in both Sz and BD, which remains stable during the early course of the illness, with no evidence of either progression or remission.

Keywords

DTIfirst episode psychosisFWputative neuroinflammatory biomarker
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 6 , April 2021 , pp. 1001 - 1010
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Copyright
Copyright © Cambridge University Press 2020

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References

Al-Amin, M. M., Nasir Uddin, M. M., & Mahmud Reza, H. (2013). Effects of antipsychotics on the inflammatory response system of patients with schizophrenia in peripheral blood mononuclear cell cultures. Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology, 11, 144–151.CrossRefGoogle ScholarPubMed
Althouse, A. D. (2016). Adjust for multiple comparisons? It's not that simple. The Annals of Thoracic Surgery, 101, 1644–1645.CrossRefGoogle Scholar
Andreasen, N. C. (1983a). The scale for the assessment of negative symptoms (SANS). Iowa City: University of Iowa.Google Scholar
Andreasen, N. C. (1983b). The scale for the assessment of positive symptoms (SAPS). Iowa City: University of Iowa.Google Scholar
Andersson, J. L., Skare, S., & Ashburner, J. (2003). How to correct susceptibility distortions in spin-echo echo-planar images: Application to diffusion tensor imaging. Neuroimage, 20, 870–888.CrossRefGoogle ScholarPubMed
Barch, D. M., Carter, C. S., MacDonald, A. W., 3rd, Braver, T. S., & Cohen, J. D. (2003). Context-processing deficits in schizophrenia: diagnostic specificity, 4-week course, and relationships to clinical symptoms. Journal of Abnormal Psychology, 112, 132–143.CrossRefGoogle ScholarPubMed
Barr, C. E., Mednick, S. A., & Munk-Jorgensen, P. (1990). Exposure to influenza epidemics during gestation and adult schizophrenia. A 40-year study. Archives of General Psychiatry, 47, 869–874.CrossRefGoogle ScholarPubMed
Behrens, T. E. J., Berg, H. J., Jbabdi, S., Rushworth, M. F. S., & Woolrich, M. W. (2007). Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? NeuroImage, 34, 144–155.CrossRefGoogle ScholarPubMed
Bilbo, S. D., & Schwarz, J. M. (2012). The immune system and developmental programming of brain and behavior. Frontiers in Neuroendocrinology, 33, 267–286.CrossRefGoogle ScholarPubMed
Brietzke, E., Stertz, L., Fernandes, B. S., Kauer-Sant'anna, M., Mascarenhas, M., Escosteguy Vargas, A., … Kapczinski, F. (2009). Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. Journal of Affective Disorders, 116, 214–217.CrossRefGoogle ScholarPubMed
Brown, A. S. (2006). Prenatal infection as a risk factor for schizophrenia. Schizophrenia Bulletin, 32, 200–202.CrossRefGoogle Scholar
Brown, A. S., & Derkits, E. J. (2010). Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. The American Journal of Psychiatry, 167, 261–280.CrossRefGoogle ScholarPubMed
Bullmore, E. T., & Lynall, M. E. (2014). Immunologic therapeutics and psychotic disorders. Biological Psychiatry, 75, 260–261.CrossRefGoogle ScholarPubMed
Carter, C. S., Bullmore, E. T., & Harrison, P. (2014). Is there a flame in the brain in psychosis? Biological Psychiatry, 75, 258–259.CrossRefGoogle Scholar
Chad, J. A., Pasternak, O., Salat, D. H., & Chen, J. J. (2018). Re-examining age-related differences in white matter microstructure with free-water corrected diffusion tensor imaging. Neurobiology of Aging, 71, 161–170.CrossRefGoogle ScholarPubMed
Clark, K., Narr, K. L., O'neill, J., Levitt, J., Siddarth, P., Phillips, O., … Caplan, R. (2012). White matter integrity, language, and childhood onset schizophrenia. Schizophrenia Research, 138, 150–156.CrossRefGoogle ScholarPubMed
Deakin, J., Lennox, B. R., & Zandi, M. S. (2014). Antibodies to the N-methyl-D-aspartate receptor and other synaptic proteins in psychosis. Biological Psychiatry, 75, 284–291.CrossRefGoogle Scholar
Di Biase, M. A., Katabi, G., Piontkewitz, Y., Cetin-Karayumak, S., Weiner, I., & Pasternak, O. (2020). Increased extracellular free-water in adult male rats following in utero exposure to maternal immune activation. Brain, Behavior, and Immunity, 83, 283–287.CrossRefGoogle ScholarPubMed
Douaud, G., Mackay, C., Andersson, J., James, S., Quested, D., Ray, M. K., … James, A. (2009). Schizophrenia delays and alters maturation of the brain in adolescence. Brain, 132, 2437–2448.CrossRefGoogle ScholarPubMed
Feinberg, I. (1982). Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence? Journal of Psychiatric Research, 17, 319–334.CrossRefGoogle ScholarPubMed
Filippi, M., Canu, E., Gasparotti, R., Agosta, F., Valsecchi, P., Lodoli, G., … Sacchetti, E. (2014). Patterns of brain structural changes in first-contact, antipsychotic drug-naïve patients with schizophrenia. American Journal of Neuroradiology, 35, 30–37.CrossRefGoogle ScholarPubMed
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (eds) (2002). Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition. (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute.Google Scholar
Fischl, B., Van Der Kouwe, A., Destrieux, C., Halgren, E., Segonne, F., Salat, D. H., … Dale, A. M. (2004). Automatically parcellating the human cerebral cortex. Cerebral Cortex, 14, 11–22.CrossRefGoogle ScholarPubMed
Foong, J., Symms, M. R., Barker, G. J., Maier, M., Miller, D. H., & Ron, M. A. (2002). Investigating regional white matter in schizophrenia using diffusion tensor imaging. Neuroreport, 13, 333–336.CrossRefGoogle ScholarPubMed
Goldsmith, D. R., Rapaport, M. H., & Miller, B. J. (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
Greve, D. N., & Fischl, B. (2009). Accurate and robust brain image alignment using boundary-based registration. NeuroImage, 48, 63–72.CrossRefGoogle ScholarPubMed
Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage, 17, 825–841.CrossRefGoogle ScholarPubMed
Jones, D. K., Catani, M., Pierpaoli, C., Reeves, S. J., Shergill, S. S., O'sullivan, M., … Howard, R. J. (2005). A diffusion tensor magnetic resonance imaging study of frontal cortex connections in very-late-onset schizophrenia-like psychosis. The American Journal of Geriatric Psychiatry, 13, 1092–1099.CrossRefGoogle ScholarPubMed
Kato, T. A., Monji, A., Mizoguchi, Y., Hashioka, S., Horikawa, H., Seki, Y., … Kanba, S. (2011). Anti-inflammatory properties of antipsychotics via microglia modulations: Are antipsychotics a ‘Fire Extinguisher’ in the brain of schizophrenia? Mini-Reviews in Medicinal Chemistry, 11, 565–574.CrossRefGoogle ScholarPubMed
Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., … Donohoe, G. (2017). Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA schizophrenia DTI working group. Molecular Psychiatry, 23, 1261.CrossRefGoogle ScholarPubMed
Knöchel, C., O'dwyer, L., Alves, G., Reinke, B., Magerkurth, J., Rotarska-Jagiela, A., … Oertel-Knöchel, V. (2012). Association between white matter fiber integrity and subclinical psychotic symptoms in schizophrenia patients and unaffected relatives. Schizophrenia Research, 140, 129–135.CrossRefGoogle ScholarPubMed
Kunz, M., Cereser, K. M., Goi, P. D., Fries, G. R., Teixeira, A. L., Fernandes, B. S., … Gama, C. S. (2011). Serum levels of IL-6, IL-10 and TNF-alpha in patients with bipolar disorder and schizophrenia: Differences in pro- and anti-inflammatory balance. Revista Brasileira de Psiquiatria, 33, 268–274.Google ScholarPubMed
Lawrie, S. M., Hall, J., Mcintosh, A. M., Owens, D. G. C., & Johnstone, E. C. (2010). The ‘continuum of psychosis’: Scientifically unproven and clinically impractical. British Journal of Psychiatry, 197, 423–425.CrossRefGoogle ScholarPubMed
Lesh, T. A., Maddock, R. J., Howell, A., Wang, H., Tanase, C., Daniel Ragland, J., … Carter, C. S. (2019). Extracellular free water and glutathione in first-episode psychosis – a multimodal investigation of an inflammatory model for psychosis. Molecular Psychiatry. doi: 10.1038/s41380-019-0428-y.Google Scholar
Lewis, S. W., & Murray, R. M. (1987). Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia. Journal of Psychiatric Research, 21, 413–421.CrossRefGoogle ScholarPubMed
Lo, W. D., Wolny, A. C., Timan, C., Shin, D., & Hinkle, G. H. (1993). Blood-brain barrier permeability and the brain extracellular space in acute cerebral inflammation. Journal of the Neurological Sciences, 118, 188–193.CrossRefGoogle ScholarPubMed
Lyall, A. E., Pasternak, O., Robinson, D. G., Newell, D., Trampush, J. W., Gallego, J. A., … Szeszko, P. R. (2018). Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Molecular psychiatry, 23, 701–707.CrossRefGoogle ScholarPubMed
Macey, P. M., Thomas, M. A., & Henderson, L. A. (2018). DTI-based upper limit of voxel free water fraction. Heliyon, 4, e00700–e00700.CrossRefGoogle ScholarPubMed
Maier-Hein, K. H., Westin, C. F., Shenton, M. E., Weiner, M. W., Raj, A., Thomann, P., … Pasternak, O. (2015). Widespread white matter degeneration preceding the onset of dementia. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 11, 485–493, e2.CrossRefGoogle ScholarPubMed
Mandl, R. C. W., Pasternak, O., Cahn, W., Kubicki, M., Kahn, R. S., Shenton, M. E., & Hulshoff Pol, H. E. (2015). Comparing free water imaging and magnetization transfer measurements in schizophrenia. Schizophrenia Research, 161 , 126–132.CrossRefGoogle Scholar
Mednick, S. A., Machon, R. A., Huttunen, M. O., & Bonett, D. (1988). Adult schizophrenia following prenatal exposure to an influenza epidemic. Archives of General Psychiatry, 45, 189–192.CrossRefGoogle Scholar
Miller, B. J., Buckley, P., Seabolt, W., Mellor, A., & Kirkpatrick, B. (2011). Meta-analysis of cytokine alterations in schizophrenia: Clinical status and antipsychotic effects. Biological psychiatry, 70, 663–671.CrossRefGoogle ScholarPubMed
Murray, R. M., Sham, P., Van Os, J., Zanelli, J., Cannon, M., & Mcdonald, C. (2004). A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder. Schizophrenia Research, 71, 405–416.CrossRefGoogle ScholarPubMed
Oestreich, L. K. L., Lyall, A. E., Pasternak, O., Kikinis, Z., Newell, D. T., Savadjiev, P., … Mccarthy-Jones, S. (2017). Characterizing white matter changes in chronic schizophrenia: A free-water imaging multi-site study. Schizophrenia Research, 189, 153–161.CrossRefGoogle ScholarPubMed
Oguz, I., Farzinfar, M., Matsui, J., Budin, F., Liu, Z., Gerig, G., … Styner, M. (2014). DTIPrep: Quality control of diffusion-weighted images. Frontiers in Neuroinformatics, 8, 4.CrossRefGoogle ScholarPubMed
Overall, J. E. (1974). The brief psychiatric rating scale in psychopharmacology research. In Psychological measurements in psychopharmacology. Oxford, England: S. Karger.Google Scholar
Pasternak, O., Kelly, S., Sydnor, V. J., & Shenton, M. E. (2018). Advances in microstructural diffusion neuroimaging for psychiatric disorders. NeuroImage, 182, 259–282.CrossRefGoogle ScholarPubMed
Pasternak, O., Shenton, M. E., & Westin, C. F. (2012a). Estimation of extracellular volume from regularized multi-shell diffusion MRI. Medical Image Computing and Computer-assisted Intervention , 15, 305–312.Google Scholar
Pasternak, O., Sochen, N., Gur, Y., Intrator, N., & Assaf, Y. (2009). Free water elimination and mapping from diffusion MRI. Magnetic Resonance in Medicine, 62, 717–730.CrossRefGoogle ScholarPubMed
Pasternak, O., Westin, C. F., Bouix, S., Seidman, L. J., Goldstein, J. M., Woo, T. U., … Kubicki, M. (2012b). Excessive extracellular volume reveals a neurodegenerative pattern in schizophrenia onset. Journal of Neuroscience, 32, 17365–17372.CrossRefGoogle Scholar
Peters, B. D., Blaas, J., & De Haan, L. (2010). Diffusion tensor imaging in the early phase of schizophrenia: What have we learned? Journal of Psychiatric Research, 44, 993–1004.CrossRefGoogle ScholarPubMed
Price, G., Bagary, M. S., Cercignani, M., Altmann, D. R., & Ron, M. A. (2005). The corpus callosum in first episode schizophrenia: A diffusion tensor imaging study. Journal of Neurology Neurosurgery & Psychiatry, 76, 585–587.CrossRefGoogle ScholarPubMed
Rae, C. L., Davies, G., Garfinkel, S. N., Gabel, M. C., Dowell, N. G., Cercignani, M., … Critchley, H. D. (2017). Deficits in neurite density underlie white matter structure abnormalities in first-episode psychosis. Biological Psychiatry, 82, 716–725.CrossRefGoogle ScholarPubMed
Salimi-Khorshidi, G., Smith, S. M., & Nichols, T. E. (2011). Adjusting the effect of nonstationarity in cluster-based and TFCE inference. NeuroImage, 54, 2006–2019.CrossRefGoogle ScholarPubMed
Schmidt, A., Lenz, C., Smieskova, R., Harrisberger, F., Walter, A., Riecher-Rössler, A., … Borgwardt, S. J. (2015). Brain diffusion changes in emerging psychosis and the impact of state-dependent psychopathology. Neurosignals, 23, 71–83.CrossRefGoogle ScholarPubMed
Sekar, A., Bialas, A. R., De Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., … Mccarroll, S. A. (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 530, 177–183.CrossRefGoogle ScholarPubMed
Simonova, Z., Svoboda, J., Orkand, P., Bernard, C. C., Lassmann, H., & Sykova, E. (1996). Changes of extracellular space volume and tortuosity in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis. Physiological Research, 45, 11–22.Google ScholarPubMed
Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C. E., … Behrens, T. E. (2006). Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data. Neuroimage, 31, 1487–1505.CrossRefGoogle ScholarPubMed
Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H., … Matthews, P. M. (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage, 23, S208–S219.CrossRefGoogle ScholarPubMed
Sugino, H., Futamura, T., Mitsumoto, Y., Maeda, K., & Marunaka, Y. (2009). Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33, 303–307.CrossRefGoogle ScholarPubMed
The Schizophrenia Psychiatric Genome-Wide Association Study, C., Ripke, S., Sanders, A. R., Kendler, K. S., Levinson, D. F., Sklar, P., Holmans, P. A., … Gejman, P. V. (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43, 969.Google Scholar
Tuozzo, C., Lyall, A. E., Pasternak, O., James, A. C. D., Crow, T. J., & Kubicki, M. (2018). Patients with chronic bipolar disorder exhibit widespread increases in extracellular free water. Bipolar Disorders, 20, 523–530.CrossRefGoogle ScholarPubMed
Wheeler, A. L., & Voineskos, A. N. (2014). A review of structural neuroimaging in schizophrenia: From connectivity to connectomics. Frontiers in Human Neuroscience, 8, 653–653.CrossRefGoogle ScholarPubMed
Winkler, A. M., Ridgway, G. R., Webster, M. A., Smith, S. M., & Nichols, T. E. (2014). Permutation inference for the general linear model. Neuroimage, 92, 381–397.CrossRefGoogle ScholarPubMed
Zajkowska, Z., & Mondelli, V. (2014). First-episode psychosis: An inflammatory state? Neuroimmunomodulation, 21, 102–108.CrossRefGoogle Scholar
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