MRI Study of Brain Activity and Risk for Depression in Adolescents
| Status: | Completed |
|---|---|
| Conditions: | Anxiety, Depression, Depression, Major Depression Disorder (MDD) |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 10 - 55 |
| Updated: | 10/8/2017 |
| Start Date: | October 12, 2002 |
| End Date: | October 27, 2016 |
Neural Circuitry and Risk for Depression in Adolescents: A Study Using Functional Magnetic Resonance Imaging
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.
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.
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.
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.
- OFFSPRING SUBJECTS - INCLUSION CRITERIA:
Age: 10-30.
Can give consent/assent. Parents will provide consent for all minors.
All subjects will have IQ greater than 80.
High risk Psychopathology: Offspring of adults with a history of MDD.
Low risk Psychopathology: Offspring of adults with no history of MDD and low developmental
levels of emotion dysregulation. Subjects born to parents with only anxiety disorders will
be included in this group.
OFFSPRING SUBJECTS - EXCLUSION CRITERIA:
Any medical condition that increases risk for MRI (e.g. pacemaker, metallic foreign body in
eye).
Pregnancy:
Both groups: All subjects will be free of current impairing affective disorders, separation
anxiety disorder, social anxiety disorder, panic disorder, generalized anxiety disorder,
PTSD, ADHD, as well as lifetime history of substance dependence, psychosis, pervasive
developmental disorder, major affective disorder, obsessive compulsive disorder, conduct
disorder, anorexia. All subjects will be born to parents with no history of schizophrenia
or bipolar disorder.
PARENT SUBJECTS - INCLUSION CRITERIA:
Age: 18-55
Can give consent/assent
Offspring: All subjects will have offspring participating in this same protocol.
Have an IQ greater than 80
Past history of MDD
No lifetime history of MDD
ADULT SUBJECTS - EXCLUSION CRITERIA:
Any medical condition that increases risk for MRI (e.g. pacemaker, metallic foreign body in
eye)
Pregnancy:
Both groups: All subjects will be free of current significantly impairing affective
disorders, psychotropic medications, as well as lifetime history of substance dependence,
psychosis, conduct disorder, or anorexia.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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