Schizophrenia Research
Volume 134, Issue 1 , Pages 1-9, January 2012

Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: A preliminary study

  • Dylan G. Gee

      Affiliations

    • University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA
    • ,
  • Katherine H. Karlsgodt

      Affiliations

    • University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA
    • ,
  • Theo G.M. van Erp

      Affiliations

    • Department of Psychiatry, University of California Irvine, USA
    • ,
  • Carrie E. Bearden

      Affiliations

    • University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA
    • ,
  • Matthew D. Lieberman

      Affiliations

    • University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA
    • ,
  • Aysenil Belger

      Affiliations

    • University of North Carolina, Chapel Hill, Department of Psychiatry, Chapel Hill, NC, USA
    • ,
  • Diana O. Perkins

      Affiliations

    • University of North Carolina, Chapel Hill, Department of Psychiatry, Chapel Hill, NC, USA
    • ,
  • Doreen M. Olvet

      Affiliations

    • Zucker Hillside Hospital, Department of Psychiatry Research, Glen Oaks, NY, USA
    • ,
  • Barbara A. Cornblatt

      Affiliations

    • Zucker Hillside Hospital, Department of Psychiatry Research, Glen Oaks, NY, USA
    • ,
  • Todd Constable

      Affiliations

    • Yale University, Department of Psychiatry, New Haven, CT, USA
    • ,
  • Scott W. Woods

      Affiliations

    • Yale University, Department of Psychiatry, New Haven, CT, USA
    • ,
  • Jean Addington

      Affiliations

    • University of Calgary, Department of Psychiatry, Calgary, Alberta, Canada
    • ,
  • Kristin S. Cadenhead

      Affiliations

    • University of California, San Diego, Department of Psychiatry, La Jolla, CA, USA
    • ,
  • Thomas H. McGlashan

      Affiliations

    • Yale University, Department of Psychiatry, New Haven, CT, USA
    • ,
  • Larry J. Seidman

      Affiliations

    • Beth Israel Deaconess Medical Center, Department of Psychiatry, Boston, MA, USA
    • ,
  • Ming T. Tsuang

      Affiliations

    • University of California, San Diego, Department of Psychiatry, La Jolla, CA, USA
    • ,
  • Elaine F. Walker

      Affiliations

    • Emory University, Department of Psychology, Atlanta, GA, USA
    • ,
  • Tyrone D. Cannon

      Affiliations

    • University of California, Los Angeles, Departments of Psychology and Psychiatry, Los Angeles, CA, USA
    • Corresponding Author InformationCorresponding author at: University of California, Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095–1563. Tel.: +1 310 794 9673; fax: +1 310 794 9740.
    • ,
  • on behalf of the NAPLS Consortium

      Affiliations

    • A complete list of study personnel involved in the NAPLS Consortium appears in the Appendix.

Received 23 April 2011; received in revised form 6 October 2011; accepted 13 October 2011. published online 07 November 2011.

Abstract 

Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning.

Keywords: Psychosis, Brain development, Emotion, Amygdala, Prefrontal cortex, fMRI

 

PII: S0920-9964(11)00540-8

doi:10.1016/j.schres.2011.10.005

Schizophrenia Research
Volume 134, Issue 1 , Pages 1-9, January 2012

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