MRI Study of Brain Activity and Risk for Depression in Adolescents
Condition: Involutional Depression; Anxiety Disorders
MeSH terms: Depression; Depressive Disorder; Anxiety Disorders; Depressive Disorder, Major
Study type: Observational

Summary: 
      Anxiety in children of parents with major depressive disorder (MDD) poses a particularly high
      risk for later-life MDD. In adults, MDD involves dysfunction in prefrontal brain regions that
      regulate attention to emotional stimuli. These abnormalities: i) have been found primarily in
      adults with specific familial forms of MDD; ii) persist after recovery from MDD, and iii)
      relate to anxiety. These findings raise the possibility that risk for MDD is tied to
      dysfunction in prefrontal regions involved in regulation of emotion, which possibly manifests
      as early-life anxiety. If this possibility were confirmed in never-depressed adolescents at
      high risk for MDD, the findings would provide key insights into the developmental
      neurobiology of MDD. The goal of this protocol is to study the neural substrate of risk for
      MDD in young people. This protocol tests the hypothesis that adolescents at high risk for MDD
      by virtue of childhood anxiety and parental history of MDD exhibit dysfunction in prefrontal
      cortex and amygdala, regions involved in emotion regulation. This goal will be accomplished
      through fMRI studies of emotion regulation in high and low-risk adolescents.

      For this research, at-risk adolescents will be recruited from participants in an NIMH-funded
      extramural study at New York University (NYU) examining the biology of risk for anxiety and
      depressive disorders. Over a three-year period, 45 high-risk probands and 60 low-risk
      comparisons will be studied, including 20 comparisons from the NYU sample and 40 from the
      Washington DC metropolitan area. In the present protocol, to be conducted at NIH, subjects
      will undergo volumetric MRI scans to assess structural abnormalities in the prefrontal cortex
      and medial temporal lobe. They will complete a series of four out-of-scanner cognitive tasks
      and two fMRI-based cognitive tasks that measure modulation of attention to emotional stimuli.
      The fMRI tasks are hypothesized to differentially engage the prefrontal cortex and amygdala
      in low vs. high risk subjects. These tasks will be used to test the hypothesis that at-risk
      individuals exhibit enhanced amygdala and reduced prefrontal activation on the fMRI
      emotion/attention tasks.
    

Detailed description: 
      Parental history of major depressive disorder poses a particularly high risk for later-life
      MDD. In adults, MDD involves dysfunction in subcortical brain regions related to emotional
      responsiveness, such as the amygdala, and in cortical brain regions that interface cognitive
      and emotional processes. These abnormalities: i) have been found primarily in adults with
      specific familial forms of MDD; ii) persist after recovery from MDD, and iii) relate to
      anxiety. These findings raise the possibility that risk for MDD is tied to dysfunction in
      emotional circuits themselves or in prefrontal regions involved in regulation of emotion. If
      this possibility were confirmed in never-depressed adolescents at high risk for MDD, the
      findings would provide key insights into the developmental neurobiology of MDD. The goal of
      this protocol is to study the neural substrate of risk for MDD in young people. This protocol
      tests the hypothesis that adolescents at high risk for MDD by virtue of parental history of
      MDD exhibit dysfunction in prefrontal cortex, amygdala, and other subcortical regions
      involved in emotion and emotion regulation. This goal will be accomplished through fMRI
      studies of edmotion provocation in high and low-risk adolescents.

      For this research, at-risk adolescents will be recruited from participants in NIMH-funded
      extramural studies at New York University, Brown University, and Columbia University
      examining the biology of risk for anxiety and depressive disorders. Over a three-year period,
      data on each measure of interest will be obtained in 100 high-risk probands and 100 low-risk
      comparisons. In addition, a sub-set of parents of these adolescents (n=100) also will be
      studied using identical procedures. In the present protocol, to be conducted at NIH, subjects
      will undergo volumetric MRI scans to assess structural abnormalities in the prefrontal cortex
      and medial temporal lobe. They will complete a series of out-of-scanner cognitive tasks and
      fMRI-based cognitive tasks. Two of these tasks measure modulation of attention to emotional
      stimuli; the third task measures engagement of temporal and prefrontal regions during social
      interactions. For these types of tasks, prior studies in adolescents with ongoing mood and
      anxiety disorders demonstrate hypothesized abnormalities in brain engagement. The current
      study is designed to examine the degree to which comparable findings emerge in unaffected
      adolescents at risk for mood and anxiety disorders.
    

Keywords: Attention; Emotion; Amygdala; Prefrontal Cortex; Facial Expression; Magnetic Resonance Imaging; fMRI; Depression; Anxiety; Adolescence; Children