CoChat
Sign Up
Cited by 229Schizophrenia research and treatmentAdvanced Neuroimaging Techniques and ApplicationsPsychopathy, Forensic Psychiatry, Sexual Offending

White matter integrity and prediction of social and role functioning in subjects at ultra-high risk for psychosis

Open access
Karlsgodt, Katherine H., Niendam, Tara A., Bearden, Carrie E., Cannon, Tyrone D.·2009·Biological Psychiatry
DOI 10.1016/j.biopsych.2009.03.013PMC PMC2805703
Open this paper in CoChat — free account

Abstract

Background White matter microstructural disruptions have been observed in patients with schizophrenia. However, whether changes exist prior to disease onset or in high-risk individuals is unclear. Here, we investigated white matter integrity, as assessed by diffusion tensor imaging (DTI), in individuals at ultra-high risk for psychosis (UHR) relative to healthy control subjects (HC) and the relationship between baseline DTI measures and functional outcome over time. Methods Thirty-six UHR participants and 25 HCs completed baseline DTI scans. Subjects also completed clinical follow-up assessments approximately 6 months (26 subjects) and 15 months (13 subjects) later. We used a rigorous registration approach (Tract-Based Spatial Statistics [TBSS]) to examine fractional anisotropy (FA) in six major white matter tracts. Results Relative to the HC group, UHR subjects showed lower baseline FA in the superior longitudinal fasciculus, the major frontoparietal white matter connection. Cross-sectional analyses demonstrated that UHR youth failed to show the same age-associated increases in FA in the medial temporal lobe (MTL) and inferior longitudinal fasciculus as HCs. Finally, lower baseline FA in the MTL and inferior longitudinal fasciculus predicted deterioration in social and role functioning in UHR participants at 15-month follow-up. Conclusions This is the first investigation of white matter microstructural alterations in a clinical high-risk sample. Our findings indicate that white matter development may be altered in youth at risk for psychosis, possibly due to disrupted developmental mechanisms, and further, that white matter integrity may be predictive of functional outcome.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2009.03.013

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Among familial high-risk schizophrenia studies, only a minority find cingulum changes, with other structures more often affected.

    “Only a minority of these familial studies find cingulum changes, with other structures more often affected (e.g., Clark et al., 2011; Hoptman et al., 2008; Karlsgodt et al., 2009; Maniega et al., 2008).”

    From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as Karlsgodt et al., 2009

    The Methods (Participants; Data Analysis) describe an ultra-high-risk group defined by prodromal criteria, not a specifically familial high-risk sample, and include the cingulate bundle among the regions examined. The Results (Analysis I) find reduced FA in the superior longitudinal fasciculus but no significant difference in the other regions. This supports the paper as an example of a non-cingulum finding, but it does not establish that only a minority of familial studies find cingulum changes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 65 · Cited by 229

Research works printed but not linked: 58

  1. [2]Cannon TD van Erp TG Huttunen M Lonnqvist J Salonen O Valanne L 1998 Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls Arch Gen Psychiatry 55 1084 1091 9862551
  2. [3]Wright IC Rabe-Hesketh S Woodruff PW David AS Murray RM Bullmore ET 2000 Meta-analysis of regional brain volumes in schizophrenia Am J Psychiatry 157 16 25 10618008
  3. [4]Sachdev P Brodaty H 1999 Quantitative study of signal hyperintensities on T2-weighted magnetic resonance imaging in late-onset schizophrenia Am J Psychiatry 156 1958 1967 10588411
  4. [6]Hakak Y Walker JR Li C Wong WH Davis KL Buxbaum JD 2001 Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia Proc Natl Acad Sci U S A 98 4746 4751 11296301 PMC31905
  5. [7]Arnold SE Rioux L 2001 Challenges, status, and opportunities for studying developmental neuropathology in adult schizophrenia Schizophr Bull 27 395 416 11596843
  6. [8]Paus T Collins DL Evans AC Leonard G Pike B Zijdenbos A 2001 Maturation of white matter in the human brain: a review of magnetic resonance studies Brain Res Bull 54 255 266 11287130
  7. [9]Karlsgodt KH Sun D Jimenez AM Lutkenhoff ES Willhite R van Erp TG Cannon TD 2008 Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia Dev Psychopathol 20 1297 1327 18838043
  8. [10]Bearden CE Rosso IM Hollister JM Sanchez LE Hadley T Cannon TD 2000 A prospective cohort study of childhood behavioral deviance and language abnormalities as predictors of adult schizophrenia Schizophr Bull 26 395 410 10885639
  9. [11]Cannon M Huttunen MO Tanskanen AJ Arseneault L Jones PB Murray RM 2002 Perinatal and childhood risk factors for later criminality and violence in schizophrenia. Longitudinal, population-based study Br J Psychiatry 180 496 501 12042227
  10. [12]Jones P Rodgers B Murray R Marmot M 1994 Child development risk factors for adult schizophrenia in the British 1946 birth cohort Lancet 344 1398 1402 7968076
  11. [13]Weinberger DR 1987 Implications of normal brain development for the pathogenesis of schizophrenia Arch Gen Psychiatry 44 660 669 3606332
  12. [14]Marenco S Weinberger DR 2000 The neurodevelopmental hypothesis of schizophrenia: following a trail of evidence from cradle to grave Dev Psychopathol 12 501 527 11014750
  13. [15]Feinberg I 1983 Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence J Psychiatr Res 17 319 334 7187776
  14. [16]Karlsgodt KH van Erp TG Poldrack RA Bearden CE Nuechterlein KH Cannon TD 2008 Diffusion tensor imaging of the superior longitudinal fasciculus and working memory in recent-onset schizophrenia Biol Psychiatry 63 512 518 17720147
  15. [17]Federspiel A Begre S Kiefer C Schroth G Strik WK Dierks T 2006 Alterations of white matter connectivity in first episode schizophrenia Neurobiol Dis 22 702 709 16624566
  16. [18]Szeszko PR Robinson DG Ashtari M Vogel J Betensky J Sevy S 2007 Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia Neuropsychopharmacology 17581532
  17. [19]Fujiwara H Namiki C Hirao K Miyata J Shimizu M Fukuyama H 2007 Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: a diffusion tensor imaging study Schizophr Res 95 215 222 17664062
  18. [20]Kubicki M Westin C Nestor PG Wible CG Frumin M Maier SE 2003 Cingulate fasiculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study Biol Psychiatry in press PMC2806222 14643084
  19. [21]Wang F Sun Z Cui L Du X Wang X Zhang H 2004 Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging Am J Psychiatry 161 573 575 14992988
  20. [22]Burns JJDBMEWHMTJECLSM 2003 Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study Br J Psychiatry 182 439 443 12724248
  21. [23]Price G Cercignani M Parker GJ Altmann DR Barnes TR Barker GJ 2008 White matter tracts in first-episode psychosis: A DTI tractography study of the uncinate fasciculus Neuroimage 39 949 955 17988894 PMC2387199
  22. [24]Kubicki M Westin C Maier S Frumin M Nestor PG Salisbury D 2002 Uncinate Fasciculus Findings in Schizophrenia: A Magnetic Resonance Diffusion Tensor Imaging Study Am J Psychiatry 159 813 820 11986136 PMC2803760
  23. [25]Nestor PG Kubicki M Gurrera RJ Niznikiewicz M Frumin M McCarley RW Shenton ME 2004 Neuropsychological correlates of diffusion tensor imaging in schizophrenia Neuropsychology 18 629 637 15506830 PMC2790923
  24. [26]Friedman JI Tang C Carpenter D Buchsbaum M Schmeidler J Flanagan L 2008 Diffusion tensor imaging findings in first-episode and chronic schizophrenia patients Am J Psychiatry 165 1024 1032 18558643
  25. [27]Cheung V Cheung C McAlonan GM Deng Y Wong JG Yip L 2008 A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia Psychol Med 38 877 885 17949516
  26. [28]O’Daly OG Frangou S Chitnis X Shergill SS 2007 Brain structural changes in schizophrenia patients with persistent hallucinations Psychiatry Res 156 15 21 17720459
  27. [29]White T Kendi AT Lehericy S Kendi M Karatekin C Guimaraes A 2007 Disruption of hippocampal connectivity in children and adolescents with schizophrenia--a voxel-based diffusion tensor imaging study Schizophr Res 90 302 307 17141478
  28. [30]Schlosser RG Nenadic I Wagner G Gullmar D von Consbruch K Kohler S 2007 White matter abnormalities and brain activation in schizophrenia: a combined DTI and fMRI study Schizophr Res 89 1 11 17085018
  29. [31]Hao Y Liu Z Jiang T Gong G Liu H Tan L 2006 White matter integrity of the whole brain is disrupted in first-episode schizophrenia Neuroreport 17 23 26 16361944
  30. [32]Szeszko PR Ardekani BA Ashtari M Kumra S Robinson DG Sevy S 2005 White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study Am J Psychiatry 162 602 605 15741480
  31. [33]Borgwardt SJ Riecher-Rossler A Dazzan P Chitnis X Aston J Drewe M 2007 Regional gray matter volume abnormalities in the at risk mental state Biol Psychiatry 61 1148 1156 17098213
  32. [34]Job DE Whalley HC Johnstone EC Lawrie SM 2005 Grey matter changes over time in high risk subjects developing schizophrenia Neuroimage 25 1023 1030 15850721
  33. [35]Whalley HC Simonotto E Moorhead W McIntosh A Marshall I Ebmeier KP 2006 Functional imaging as a predictor of schizophrenia Biol Psychiatry 60 454 462 16460690
  34. [36]Morey RA Inan S Mitchell TV Perkins DO Lieberman JA Belger A 2005 Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing Arch Gen Psychiatry 62 254 262 15753238 PMC2732718
  35. [37]Cornblatt BA Auther AM Niendam T Smith CW Zinberg J Bearden CE Cannon TD 2007 Preliminary findings for two new measures of social and role functioning in the prodromal phase of schizophrenia Schizophr Bull 33 688 702 17440198 PMC2526147
  36. [38]Niendam TA Bearden CE Johnson JK McKinley M Loewy R O’Brien M 2006 Neurocognitive performance and functional disability in the psychosis prodrome Schizophr Res 84 100 111 16563699
  37. [39]Niendam TA Bearden CE Zinberg J Johnson JK O’Brien M Cannon TD 2007 The course of neurocognition and social functioning in individuals at ultra high risk for psychosis Schizophr Bull 33 772 781 17420177 PMC2526130
  38. [41]Meyer SE Bearden CE Lux SR Gordon JL Johnson JK O’Brien MP 2005 The psychosis prodrome in adolescent patients viewed through the lens of DSM-IV J Child Adolesc Psychopharmacol 15 434 451 16092909
  39. [44]Smith SM Jenkinson M Johansen-Berg H Rueckert D Nichols TE Mackay CE 2006 Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data Neuroimage 31 1487 1505 16624579
  40. [45]Mori S Wakana S Nagae-Poetscher LM van Zijl PC 2005 MRI Atlas of Human White Matter Amsterdam Elsevier 14645885
  41. [46]Wakana S Caprihan A Panzenboeck MM Fallon JH Perry M Gollub RL 2007 Reproducibility of quantitative tractography methods applied to cerebral white matter Neuroimage 36 630 644 17481925 PMC2350213
  42. [47]Hua K Zhang J Wakana S Jiang H Li X Reich DS 2008 Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification Neuroimage 39 336 347 17931890 PMC2724595
  43. [48]Pantelis C Velakoulis D McGorry PD Wood SJ Suckling J Phillips LJ 2003 Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison Lancet 361 281 288 12559861
  44. [49]Borgwardt SJ McGuire PK Aston J Berger G Dazzan P Gschwandtner U 2007 Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis Br J Psychiatry Suppl 51 s69 75 18055941
  45. [50]Meisenzahl EM Koutsouleris N Gaser C Bottlender R Schmitt GJ McGuire P 2008 Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study Schizophr Res 102 150 162 18439804
  46. [51]Velakoulis D Wood SJ Wong MT McGorry PD Yung A Phillips L 2006 Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals Arch Gen Psychiatry 63 139 149 16461856
  47. [52]Walterfang M McGuire PK Yung AR Phillips LJ Velakoulis D Wood SJ 2008 White matter volume changes in people who develop psychosis Br J Psychiatry 193 210 215 18757979
  48. [53]Peters BD de Haan L Dekker N Blaas J Becker HE Dingemans PM 2008 White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis Neuropsychobiology 58 19 28 18781087
  49. [54]Rapoport JL Giedd JN Blumenthal J Hamburger S Jeffries N Fernandez T 1999 Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study Arch Gen Psychiatry 56 649 654 10401513
  50. [55]Giedd JN Blumenthal J Jeffries NO Castellanos FX Liu H Zijdenbos A 1999 Brain development during childhood and adolescence: a longitudinal MRI study Nat Neurosci 2 861 863 10491603
  51. [56]Nugent TF 3rd Herman DH Ordonez A Greenstein D Hayashi KM Lenane M 2007 Dynamic mapping of hippocampal development in childhood onset schizophrenia Schizophr Res 90 62 70 17161938
  52. [57]van Haren NE Pol HE Schnack HG Cahn W Brans R Carati I 2007 Progressive Brain Volume Loss in Schizophrenia Over the Course of the Illness: Evidence of Maturational Abnormalities in Early Adulthood Biol Psychiatry 17599810
  53. [58]Cannon TD van Erp TG Bearden CE Loewy R Thompson P Toga AW 2003 Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions Schizophr Bull 29 653 669 14989405
  54. [59]Waddington JL Lane A Scully PJ Larkin C O’Callaghan E 1998 Neurodevelopmental and neuroprogressive processes in schizophrenia. Antithetical or complementary, over a lifetime trajectory of disease? Psychiatr Clin North Am 21 123 149 9551494
  55. [60]Cannon TD Cornblatt B McGorry P 2007 The empirical status of the ultra high-risk (prodromal) research paradigm Schizophr Bull 33 661 664 17470445 PMC2526144
  56. [61]Hoptman MJ Nierenberg J Bertisch HC Catalano D Ardekani BA Branch CA Delisi LE 2008 A DTI study of white matter microstructure in individuals at high genetic risk for schizophrenia Schizophr Res 106 115 124 18804959
  57. [62]Price G Bagary MS Cercignani M Altmann DR Ron MA 2005 The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study J Neurol Neurosurg Psychiatry 76 585 587 15774453 PMC1739596
  58. [63]Szeszko PR Robinson DG Ashtari M Vogel J Betensky J Sevy S 2008 Clinical and neuropsychological correlates of white matter abnormalities in recent onset schizophrenia Neuropsychopharmacology 33 976 984 17581532

Authors
Karlsgodt, K. H., Niendam, T. A., Bearden, C. E., & Cannon, T. D.
Affiliations
  • University of California, Los Angeles (US)
  • University of California, Davis (US)
Corresponding author
Karlsgodt, Katherine H.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2009-09
Volume
66
Issue
6
Pages
562-569
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2009.03.013
PMC
PMC2805703
OpenAlex
W2093810348
Cited by
229
References
65
Citations by year
2026: 1 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 17 · 2019: 13 · 2018: 7 · 2017: 19 · 2016: 18 · 2015: 18 · 2014: 27 · 2013: 21 · 2012: 16
FWCI
10.21
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (F31MH068111, MH-066286, MH 14584, R01MH065079, T32MH014584, P50MH066286, 5-F31-MH068111-02, MH65079)
  • National Institute of General Medical Sciences (GM072978)
  • National Center for Research Resources (U24RR021992, RR021992)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
Keywords
clinical high risk for psychosis, white matter microstructure, fractional anisotropy, diffusion tensor imaging, social functioning, role functioning, functional outcome prediction, superior longitudinal fasciculus, inferior longitudinal fasciculus, medial temporal lobe, white matter development, schizophrenia risk
MeSH terms
Adolescent, Mental Disorders, Brain, Brain Mapping, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Male, Neuropsychological Tests, Predictive Value of Tests, Psychiatric Status Rating Scales, Risk, Social Behavior, Anisotropy, Diffusion Magnetic Resonance Imaging, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review