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Cited by 200Advanced Neuroimaging Techniques and ApplicationsSchizophrenia research and treatmentMental Health and Psychiatry

What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia

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Alba-Ferrara, L. M., de Erausquin, Gabriel A.·2013·Frontiers in Integrative Neuroscience
DOI 10.3389/fnint.2013.00009PMC PMC3593197
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Abstract

Schizophrenia is a common, severe, and chronically disabling mental illness of unknown cause. Recent MRI studies have focused attention on white matter abnormalities in schizophrenia using diffusion tensor imaging (DTI). Indices commonly derived from DTI include (1) mean diffusivity, independent of direction, (2) fractional anisotropy (FA) or relative anisotropy (RA), (3) axial diffusivity, and (4) radial diffusivity. In cerebral white matter, contributions to these indices come from fiber arrangements, degree of myelination, and axonal integrity. Relatively pure deficits in myelin result in a modest increase in radial diffusivity, without affecting axial diffusivity and with preservation of anisotropy. Although schizophrenia is not characterized by gross abnormalities of white matter, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. Since each oligodendrocyte myelinates as many as 40 axon segments, changes in the number of oligodendrocytes (OLG), and/or in the integrity of myelin sheaths, and/or axoglial contacts can have a profound impact on signal propagation and the integrity of neuronal circuits. Whereas a number of studies have revealed inconsistent decreases in anisotropy in schizophrenia, we and others have found increased FA in key subcortical tracts associated with the circuits underlying symptom generation in schizophrenia. We review data revealing increased anisotropy in dopaminergic tracts in the mesencephalon of schizophrenics and their unaffected relatives, and discuss the possible biological underpinnings and physiological significance of this finding.

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  • The rise before the fall in FA found in the present article could represent an early compensation process.

    “The rise before the fall in FA (i.e., increase before the decrease) we found in the present article, could represent an early compensation process (Alba-Ferrara and de Erausquin, 2013).”

    From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Alba-Ferrara and de Erausquin, 2013

    The Conclusions and future directions section says that increases and decreases in FA could reflect compensatory changes, supporting compensation as a possibility. It does not describe a temporal rise before a fall or identify compensation as an early process; it also says the authors consider diffuse dysregulation more likely. No page number is available in our copy. (LLM, conf=0.85)

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Research works printed but not linked: 44

  1. Alba-Ferrara L. Fernyhough C. Weis S. Mitchell R. L. C. Hausmann M. (2012). Contributions of emotional prosody comprehension deficits to the formation of auditory verbal hallucinations in schizophrenia. Clin. Psychol. Rev. 32, 244– 250 10.1016/j.cpr.2012.02.003 22459787 · DOI
  2. Boretius S. Escher A. Dallenga T. Wrzos C. Tammer R. Brück W. (2012). Assessment of lesion pathology in a new animal model of MS by multiparametric MRI and DTI. Neuroimage 59, 2678– 2688 10.1016/j.neuroimage.2011.08.051 21914485 · DOI · Paper page
  3. Braskie M. N. Jahanshad N. Stein J. L. Barysheva M. Johnson K. McMahon K. L. (2012). Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults. J. Neurosci. 32, 5964– 5972 10.1523/JNEUROSCI.5561-11.2012 22539856 PMC3393752 · DOI
  4. Calvó de Padilla M. Padilla E. Alemán G. G. Bourdieu M. Guerrero G. Strejilevich S. (2006). Temperament traits associated with risk of schizophrenia in an indigenous population of argentina. Schizophr. Res. 83, 299– 302 10.1016/j.schres.2005.12.848 16480854 · DOI
  5. Cohen-Cory S. (2002). The developing synapse: construction and modulation of synaptic structures and circuits. Science 298, 770– 776 10.1126/science.1075510 12399577 · DOI
  6. Cui L. Chen Z. Deng W. Huang X. Li M. Ma X. (2011). Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients. Psychiatry Res. 194, 347– 353 10.1016/j.pscychresns.2011.03.010 22079662 · DOI
  7. Douaud G. Smith S. Jenkinson M. Behrens T. Johansen-Berg H. Vickers J. (2007). Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. Brain 130(Pt 9), 2375– 2386 10.1093/brain/awm184 17698497 · DOI
  8. Felsky D. Voineskos A. N. Lerch J. P. Nazeri A. Shaikh S. A. Rajji T. K. (2012). Myelin-associated glycoprotein gene and brain morphometry in schizophrenia. Front. Psychiatry 3: 40 10.3389/fpsyt.2012.00040 22563322 PMC3342517 · DOI
  9. Flynn S. W. Lang D. J. Mackay A. L. Goghari V. Vavasour I. M. Whittall K. P. (2003). Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins. Mol. Psychiatry 8, 811– 820 10.1038/sj.mp.4001337 12931208 · DOI
  10. Georgieva L. Moskvina V. Peirce T. Norton N. Bray N. J. Jones L. (2006). Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 103, 12469– 12474 10.1073/pnas.0603029103 16891421 PMC1567903 · DOI
  11. Haroutunian V. Davis K. L. (2007). Introduction to the special section: myelin and oligodendrocyte abnormalities in schizophrenia. Int. J. Neuropsychopharmacol. 10, 499– 502 10.1017/S1461145706007449 17583597 · DOI
  12. Howes O. D. Kapur S. (2009). The dopamine hypothesis of schizophrenia: version III-the final common pathway. Schizophr. Bull. 35, 549– 562 10.1093/schbul/sbp006 19325164 PMC2669582 · DOI · Paper page
  13. Huang K. Tang W. Tang R. Xu Z. He Z. Li Z. (2008). Positive association between OLIG2 and schizophrenia in the chinese han population. Hum. Genet. 122, 659– 660 10.1007/s00439-007-0434-z 17934761 · DOI
  14. Hubl D. Koenig T. Strik W. Federspiel A. Kreis R. Boesch C. (2004). Pathways that make voices: white matter changes in auditory hallucinations. Arch. Gen. Psychiatry 61, 658– 668 10.1001/archpsyc.61.7.658 15237078 · DOI
  15. Katsel P. Davis K. L. Haroutunian V. (2005). Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: a gene ontology study. Schizophr. Res. 79, 157– 173 10.1016/j.schres.2005.06.007 16139990 · DOI
  16. Katsel P. Davis K. L. Li C. Tan W. Greenstein E. Kleiner Hoffman L. B. (2008). Abnormal Indices of Cell Cycle Activity in Schizophrenia and Their Potential Association with Oligodendrocytes. Neuropsychopharmacology 33, 2993– 3009 10.1038/npp.2008.19 18322470 · DOI
  17. Konrad A. Winterer G. (2008). Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon? Schizophr. Bull. 34, 72– 92 10.1093/schbul/sbm034 17485733 PMC2632386 · DOI
  18. Kubicki M. McCarley R. Westin C. F. Park H. J. Maier S. Kikinis R. (2007). A review of diffusion tensor imaging studies in schizophrenia. J. Psychiatr. Res. 41, 15– 30 10.1016/j.jpsychires.2005.05.005 16023676 PMC2768134 · DOI · Paper page
  19. Laughlin B. S. Sejnowski T. J. (2003). Communication in neuronal networks. Science 301, 1870– 1874 10.1126/science.1089662 14512617 PMC2930149 · DOI · Paper page
  20. Lim K. O. Ardekani B. A. Nierenberg J. Butler P. D. Javitt D. C. Hoptman M. J. (2006). Voxelwise correlational analyses of white matter integrity in multiple cognitive domains in schizophrenia. Am. J. Psychiatry 163, 2008– 2010 10.1176/appi.ajp.163.11.2008 17074956 PMC1950260 · DOI
  21. Mechelli A. Allen P. Amaro E. Jr. Fu C. H. Williams S. C. Brammer M. J. (2007). Misattribution of speech and impaired connectivity in patients with auditory verbal hallucinations. Hum. Brain Mapp. 28, 1213– 1222 10.1002/hbm.20341 17266108 PMC6871422 · DOI · Paper page
  22. Mitkus S. N. Hyde T. M. Vakkalanka R. Kolachana B. Weinberger D. R. Kleinman J. E. (2008). Expression of oligodendrocyte-associated genes in dorsolateral prefrontal cortex of patients with schizophrenia. Schizophr. Res. 98, 129– 138 10.1016/j.schres.2007.09.032 17964117 PMC2259271 · DOI
  23. Mittal V. A. Neumann C. Saczawa M. Walker E. F. (2008). Longitudinal progression of movement abnormalities in relation to psychotic symptoms in adolescents at high risk of schizophrenia. Arch. Gen. Psychiatry 65, 165– 171 10.1001/archgenpsychiatry.2007.23 18250254 · DOI
  24. Mulert C. Kirsch V. Whitford T. J. Alvarado J. Pelavin P. McCarley R. W. (2012). Hearing voices: a role of interhemispheric auditory connectivity? World J. Biol. Psychiatry 13, 153– 158 10.3109/15622975.2011.570789 21623667 PMC5768313 · DOI
  25. Okugawa G. Nobuhara K. Minami T. Takase K. Sugimoto T. Saito Y. (2006). Neural disorganization in the superior cerebellar peduncle and cognitive abnormality in patients with schizophrenia: a diffusion tensor imaging study. Prog. Neuropsychopharmacol. Biol. Psychiatry 30, 1408– 1412 10.1016/j.pnpbp.2006.05.014 16844275 · DOI
  26. Ozcan A. (2010). A new model for diffusion weighted MRI: complete Fourier direct MRI. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2010, 2710– 2713 10.1109/IEMBS.2010.5626530 21096205 PMC3091598 · DOI
  27. Prata D. P. Kanaan R. A. Barker G. J. Shergill S. Woolley J. Georgieva L. (2012). Risk variant of oligodendrocyte lineage transcription factor 2 is associated with reduced white matter integrity. Hum. Brain Mapp. [Epub ahead of print]. 10.1002/hbm.22045 22505278 PMC6870420 · DOI
  28. Rotarska-Jagiela A. Oertel-Knoechel V. DeMartino F. van de Ven V. Formisano E. Roebroeck A. (2009). Anatomical brain connectivity and positive symptoms of schizophrenia: a diffusion tensor imaging study. Psychiatry Res. 174, 9– 16 10.1016/j.pscychresns.2009.03.002 19767179 · DOI
  29. Seeman P. Kapur S. (2000). Schizophrenia: M. dopamine, more D2 receptors. Proc. Natl. Acad. Sci. U.S.A. 97, 7673– 7675 10884398 PMC33999
  30. Segal D. Koschnick J. R. Slegers L. H. A. Hof P. R. (2007). Oligodendrocyte pathophysiology: a new view of schizophrenia. Int. J. Neuropsychopharmacol. 10, 503– 511 10.1017/S146114570600722X 17291369 · DOI
  31. Seok J.-H. Park H.-J. Chun J. W. Lee S. K. Cho H. S. Kwon J. S. (2007). White matter abnormalities associated with auditory hallucinations in schizophrenia: a combined study of voxel-based analyses of diffusion tensor imaging and structural magnetic resonance imaging. Psychiatry Res. 156, 93– 104 10.1016/j.pscychresns.2007.02.002 17884391 · DOI · Paper page
  32. Shergill S. S. Kanaan R. A. Chitnis X. A. O'Daly O. Jones D. K. Frangou S. (2007). A diffusion tensor imaging study of fasciculi in schizophrenia. Am. J. Psychiatry 164, 467– 473 10.1176/appi.ajp.164.3.467 17329472 · DOI
  33. Strejilevich S. A. Palatnik A. Avila R. Bustin J. Cassone J. Figueroa S. (2005). Lack of extrapyramidal side effects predicts quality of life in outpatients treated with clozapine or with typical antipsychotics. Psychiatry Res. 133, 277– 280 10.1016/j.psychres.2004.10.009 15741003 · DOI
  34. Takahashi N. Sakurai T. Davis K. L. Buxbaum J. D. (2011). Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia. Prog. Neurobiol. 93, 13– 24 10.1016/j.pneurobio.2010.09.004 20950668 PMC3622281 · DOI · Paper page
  35. Tkachev D. Mimmack M. L. Huffaker S. J. Ryan M. Bahn S. (2007). Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia. Int. J. Neuropsychopharmacol. 10, 557– 563 10.1017/S1461145706007334 17291371 · DOI
  36. Turken A. Whitfield-Gabrieli S. Bammer R. Baldo J. V. Dronkers N. F. Gabrieli J. D. (2008). Cognitive processing speed and the structure of white matter pathways: convergent evidence from normal variation and lesion studies. Neuroimage 42, 1032– 1044 10.1016/j.neuroimage.2008.03.057 18602840 PMC2630965 · DOI · Paper page
  37. Uranova N. A. Vostrikov V. M. Orlovskaya D. D. Rachmanova V. I. (2004). Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the stanley neuropathology consortium. Schizophr. Res. 67, 269– 275 10.1016/S0920-9964(03)00181-6 14984887 · DOI · Paper page
  38. Uranova N. Orlovskaya D. Vikhreva O. Zimina I. Kolomeets N. Vostrikov V. (2001). Electron microscopy of oligodendroglia in severe mental illness. Brain Res. Bull. 55, 597– 610 10.1016/S0361-9230(01)00528-7 11576756 · DOI · Paper page
  39. van Schijndel J. E. van Loo K. M. van Zweeden M. Djurovic S. Andreassen O. A. Hansen T. (2009). Three-cohort targeted gene screening reveals a non-synonymous TRKA polymorphism associated with schizophrenia. J. Psychiatr. Res. 43, 1195– 1199 10.1016/j.jpsychires.2009.04.006 19435634 · DOI
  40. van Schijndel J. E. Van Zweeden M. Van Loo K. M. Djurovic S. Andreassen O. A. Hansen T. (2011). Dual association of a TRKA polymorphism with schizophrenia. Psychiatr. Genet. 21, 125– 131 10.1097/YPG.0b013e3283437194 21317683 · DOI
  41. Walther S. Federspiel A. Horn H. Razavi N. Wiest R. Dierks T. (2011). Alterations of white matter integrity related to motor activity in schizophrenia. Neurobiol. Dis. 42, 276– 283 10.1016/j.nbd.2011.01.017 21296665 · DOI
  42. Whitford T. J. Ford J. M. Mathalon D. H. Kubicki M. Shenton M. E. (2012). Schizophrenia, myelination, and delayed corollary discharges: a hypothesis. Schizophr. Bull. 38, 486– 494 10.1093/schbul/sbq105 20855415 PMC3329979 · DOI · Paper page
  43. Whitford T. J. Mathalon D. H. Shenton M. E. Roach B. J. Bammer R. Adcock R. A. (2011). Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia. Psychol. Med. 41, 959– 969 10.1017/S0033291710001376 20663254 PMC3807011 · DOI · Paper page
  44. Zhang D. Guo L. Hu X. Li K. Zhao Q. Liu T. (2012). Increased cortico-subcortical functional connectivity in schizophrenia. Brain Imaging Behav. 6, 27– 35 10.1007/s11682-011-9138-z 22002475 · DOI

Cited by

Sorted by citations

Authors
Alba-Ferrara, L. M., & de Erausquin, G. A.
Venue
Frontiers in Integrative Neuroscience
Publisher
Frontiers Media SA
Published
2013
Volume
7
Pages
9-9
ISSN
1662-5145 (ISSN-L)
DOI
10.3389/fnint.2013.00009
PMC
PMC3593197
OpenAlex
W2122102786
Cited by
200
References
4
Citations by year
2026: 7 · 2025: 12 · 2024: 10 · 2023: 22 · 2022: 27 · 2021: 21 · 2020: 19 · 2019: 17 · 2018: 16 · 2017: 12 · 2016: 10 · 2015: 11 · 2014: 10 · 2013: 6
FWCI
9.57
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Integrative Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (K08MH077220)
  • Fogarty International Center (R21TW007882)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords
schizophrenia, white matter, anisotropy, fractional anisotropy, relative anisotropy, oligodendrocytes, myelination, midbrain, axonal integrity, diffusion tensor imaging

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