Protocol Number: 03-M-0014

Title:

Neural Circuitry and Risk for Depression in Adolescents: A Study Using Functional Magnetic Resonance Imaging

Number:

03-M-0014

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.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

ADOLESCENT SUBJECTS - INCLUSION CRITERIA:

Age: 10-17.

Can give consent/assent. Parents will provide consent for all minors.

All subjects will have IQ greater than 80.

High risk: Offspring of adults with a history of MDD.

Low risk: Offspring of adults with no history of MDD and low developmental levels of emotion dysregulation. 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.

ADOLESCENT SUBJECTS - EXCLUSION CRITERIA:

Any medical condition that increases risk for MRI (e.g. pacemaker, metallic foreign body in eye).

Pregnancy.

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.

ADULT SUBJECTS - INCLUSION CRITERIA:

Age: 18-55

Can give consent.

Must have an offspring participating in the 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

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.

Special Instructions:

Currently Not Provided

Keywords:

Attention

Emotion

Amygdala

Prefrontal Cortex

Facial Expression

Magnetic Resonance Imaging

fMRI

Depression

Anxiety

Adolescence

Recruitment Keyword(s):

Depression

Anxiety

Adolescence

Children

Condition(s):

Involutional Depression

Anxiety Disorders

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Mental Health

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Drevets WC, Ongur D, Price JL. Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders. Mol Psychiatry. 1998 May;3(3):220-6, 190-1. Review.

Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol. 2001 Apr;11(2):240-9.Review.

Drevets WC. Neuroimaging studies of mood disorders. Biol Psychiatry. 2000 Oct 15;48(8):813-29.

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