New Research
Relation Between Amygdala Structure and Function in Adolescents With Bipolar Disorder

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Abstract

Objective

Previous study supports the presence of reduced volume and elevated response to emotional stimuli in amygdala in adolescents with bipolar disorder (BD). In the present study, structural and functional magnetic resonance imaging scans were obtained during the same neuroimaging session to examine amygdala structure-function relations in adolescents with BD. We hypothesized that amygdala volume would be inversely associated with amygdala response to emotional stimuli, such that BD participants with the smallest amygdala volumes would exhibit the highest amygdala response.

Method

Fifty-one adolescents (21 with BD I and 30 control adolescents, ages 10-18 years) underwent structural and functional magnetic resonance imaging scans. Amygdala volume (n = 49) and signal change (n = 44) during emotional face processing were compared between groups, and structure-function correlations were examined within the BD group (n = 16).

Results

Adolescents with BD showed decreased amygdala volume (p = .009) and increased amygdala response to emotional faces (p = .043). There was no significant interaction between diagnosis and emotion type. A significant inverse association between amygdala volume and activation during emotional face processing was observed (r = −0.54, p = .029).

Conclusions

Decreased volume and increased response to emotional stimuli in the amygdala in adolescents with BD are consistent with previous reports. This study represents the first report, to our knowledge, of the two findings in the same adolescent BD sample and supports an amygdala structure-function relation characterized by an inverse association between volume and response to emotional stimuli. This preliminary finding requires replication and suggests a possible pathophysiological link between abnormalities in amygdala structure and response to emotional stimuli in BD. J. Am. Acad. Child Adolesc. Psychiatry,2009;48(6):636-642.

Section snippets

Participants

Participants consisted of 21 adolescent outpatients with BD I (47.6% female subjects, mean age 15.10 years, SD 2.05 years) and 30 control adolescents (36.7% female subjects, mean age 14.17 years, SD 2.10 years). These data have not been reported previously, excluding presentation in part at the 63rd Annual Scientific Meeting and Convention of the Society of Biological Psychiatry.23 Participants with BD were referred from a University Medical Center, a Veterans Affairs Healthcare System, and the

Results

The control and BD groups did not differ statistically in age (p = .12) or sex distribution (p = .43). With regard to amygdala volume, two participants with BD showed excessive movement and were excluded from volumetric analyses. There was a significant main effect of diagnosis such that amygdala volumes were significantly smaller in the adolescents with BD relative to the control adolescents (F1,46 = 7.44, p = .009).Figure 1 shows areas of reduced volume, displaying the localization of

Discussion

We observed both significantly reduced amygdala volume and significantly increased amygdala response to emotional stimuli in a sample of adolescents with BD relative to controls. The structural and functional neuroimaging data for each participant were acquired in the same session. Moreover, an association was revealed between the structural and functional abnormalities, such that adolescents with BD who had the smallest amygdala volume exhibited the highest amygdala activation when processing

References (49)

  • NS Lawrence et al.

    Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression

    Biol Psychiatry

    (2004)
  • JD Lish et al.

    Family psychiatric screening instruments for epidemiologic studies: pilot testing and validation

    Psychiatry Res

    (1995)
  • J Kaufman et al.

    Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • J Ashburner et al.

    Unified segmentation

    Neuroimage

    (2005)
  • J Ashburner et al.

    Voxel-based morphometry—the methods

    Neuroimage

    (2000)
  • JA Maldjian et al.

    An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets

    Neuroimage

    (2003)
  • S Berretta et al.

    Neuron numbers and volume of the amygdala in subjects diagnosed with bipolar disorder or schizophrenia

    Biol Psychiatry

    (2007)
  • MP Bowley et al.

    Low glial numbers in the amygdala in major depressive disorder

    Biol Psychiatry

    (2002)
  • FM Benes et al.

    The density of pyramidal and nonpyramidal neurons in anterior cingulate cortex of schizophrenic and bipolar subjects

    Biol Psychiatry

    (2001)
  • FM Benes et al.

    A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives

    Biol Psychiatry

    (1998)
  • FM Benes et al.

    GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder

    Neuropsychopharmacology

    (2001)
  • IM Rosso et al.

    Amygdala and hippocampus volumes in pediatric major depression

    Biol Psychiatry

    (2005)
  • E Leibenluft et al.

    Researching the pathophysiology of pediatric bipolar disorder

    Biol Psychiatry

    (2003)
  • EB McClure et al.

    Facial expression recognition in adolescents with mood and anxiety disorders

    Am J Psychiatry

    (2003)
  • Cited by (0)

    This article was reviewed under and accepted by Ad Hoc Editor Daniel S. Pine, M.D.

    This work was supported by grants from the National Institute of Mental Health (R01MH69747 [H.P.B.], T32MH14276 [J.H.K. and L.G.C.]), the Department of Veterans Affairs Research Enhancement Award Program (H.P.B. and L.G.C.), Howard Hughes Medical Institute (M.P.S.), NARSAD (H.P.B. and J.H.K.), the Attias Family Foundation (H.P.B.), Marcia Simon Kaplan (J.H.K.), the Ethel F. Donaghue Women's Investigator Program at Yale (H.P.B.), and the Klingenstein Foundation (J.H.K.).

    These data were presented in part at the 63rd Annual Scientific Meeting and Convention of the Society of Biological Psychiatry, May 1 to 3, 2008, Washington, DC.

    This article is dedicated to Ms. Kathleen Colonese, who was devoted to advancing research in youths with bipolar disorder and aiding the individuals with psychiatric illnesses and their families.

    The authors thank Karen Martin, R.T.R.M.R., Terry Hickey, R.T.R.M.R., and Hedy Sarofin, R.T.R.M.R., for technical expertise and the research subjects for their participation. The authors also thank all the members of the Mood Disorders Research Program Team.

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