Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives

Pawel Skudlarski, David J. Schretlen, Gunvant K. Thaker, Michael C. Stevens, Matcheri S. Keshavan, John A. Sweeney, Carol A. Tamminga, Brett A. Clementz, Kasey O'Neil, Godfrey D. Pearlson

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Objective: Both schizophrenia and bipolar disorder are hypothesized to involve disordered brain connectivity. Prior studies show low white matter integrity, measured with diffusion tensor imaging, for both disorders. The authors studied disease specificity and endophenotypic status of these abnormalities by examining patients and their unaffected relatives. Method: The 513 participants included probands with schizophrenia, probands with psychotic bipolar disorder, their firstdegree relatives, and healthy comparison subjects. Fractional anisotropy measures of white matter integrity were collected at two sites as a part of the Bipolar- Schizophrenia Network on Intermediate Phenotypes project. Relatives with cluster A or B personality characteristics were further examined. Results: Both the probands with schizophrenia and those with psychotic bipolar disorder showed lower fractional anisotropy than the comparison subjects in multiple white matter regions; differences were more marked in schizophrenia. No significant differences existed between proband groups, but in some brain regions scores on a measure of the dimensional continuum between schizophrenia and bipolar disorder, the Schizo-Bipolar Scale, showed correlations with fractional anisotropy. Many regions affected in schizophrenia probands showed similar but smaller effects in relatives, with a continuous fractional anisotropy decrease from healthy subjects to relatives to cluster A/B relatives to probands. The pattern for psychotic bipolar disorder was similar but involved fewer brain regions. Effects in bipolar relatives were limited to younger subjects. Fractional anisotropy decreased with age in all groups; this decrease was exaggerated in schizophrenia but not psychotic bipolar disorder. Conclusions: Fractional anisotropy was highly heritable, supporting its value as a potential endophenotype.

Original languageEnglish (US)
Pages (from-to)886-898
Number of pages13
JournalAmerican Journal of Psychiatry
Volume170
Issue number8
DOIs
StatePublished - Aug 1 2013

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Endophenotypes
Diffusion Tensor Imaging
Bipolar Disorder
Psychotic Disorders
Anisotropy
Schizophrenia
Healthy Volunteers
Brain
White Matter
Imaging
Personality
Phenotype

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Arts and Humanities (miscellaneous)

Cite this

Skudlarski, P., Schretlen, D. J., Thaker, G. K., Stevens, M. C., Keshavan, M. S., Sweeney, J. A., ... Pearlson, G. D. (2013). Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives. American Journal of Psychiatry, 170(8), 886-898. https://doi.org/10.1176/appi.ajp.2013.12111448

Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives. / Skudlarski, Pawel; Schretlen, David J.; Thaker, Gunvant K.; Stevens, Michael C.; Keshavan, Matcheri S.; Sweeney, John A.; Tamminga, Carol A.; Clementz, Brett A.; O'Neil, Kasey; Pearlson, Godfrey D.

In: American Journal of Psychiatry, Vol. 170, No. 8, 01.08.2013, p. 886-898.

Research output: Contribution to journalArticle

Skudlarski, P, Schretlen, DJ, Thaker, GK, Stevens, MC, Keshavan, MS, Sweeney, JA, Tamminga, CA, Clementz, BA, O'Neil, K & Pearlson, GD 2013, 'Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives', American Journal of Psychiatry, vol. 170, no. 8, pp. 886-898. https://doi.org/10.1176/appi.ajp.2013.12111448
Skudlarski, Pawel ; Schretlen, David J. ; Thaker, Gunvant K. ; Stevens, Michael C. ; Keshavan, Matcheri S. ; Sweeney, John A. ; Tamminga, Carol A. ; Clementz, Brett A. ; O'Neil, Kasey ; Pearlson, Godfrey D. / Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives. In: American Journal of Psychiatry. 2013 ; Vol. 170, No. 8. pp. 886-898.
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