MRI Study of Brain Activity and Risk for Depression in Adolescents

This study will use magnetic resonance imaging (MRI) to investigate brain changes in adolescents at risk for Major Depressive Disorder. It also calls for healthy volunteers to compare to children at risk for major depression.

Official Title

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

Conditions

– Involutional Depression- Anxiety Disorders

Study Type

Observational

Study Design

Natural History

Further Details

Children whose parents have major depressive disorder (MDD) are at risk for developing MDD. Children who experience anxiety are particularly at risk. This study will examine whether the risk for MDD is associated with changes in brain regions involved in the regulation of emotion and with anxiety early in life. Adolescents who have a parent with MDD and a history of anxiety symptoms will be compared to healthy volunteer adolescents who have no family history of MDD or childhood anxiety. Participants and their parents will have three outpatient study visits to NIH. Visit 1 will include a medical history, physical examination, questionnaires on thoughts and feelings, and tests to measure intelligence. During Visit 2, participants will perform memory and problem-solving tests and taught how to do tasks similar to those they will perform during Visit 3. The tasks involve looking at pictures, remembering things, and making decisions. During some of these tasks, the participant’s eye movements will be tracked using a safe infrared light. At Visit 3, participants perform the tasks introduced on Visit 2 while in the MRI. 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, 30 high-risk probands and 45 low-risk comparisons will be studied, including 20 comparisons from the NYU sample and 25 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 MRI 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.

Study Start

Eligibility & Criteria

Genders Eligible for Study: Both Accepts Healthy VolunteersCriteria 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 MDD who have a history of childhood anxiety symptoms.Low risk: No history of parental MDD or childhood anxiety.A prior history of childhood anxiety symptoms will be an inclusion criterion, but children exhibiting current clinically significant anxiety disorders beyond specific phobias will be excluded.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.

Total Enrolment

95

Contact Details

[1] National Institute of Mental Health (NIMH) (US)