Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder

The purpose of this study is determine whether single and paired-pulse transcranial magnetic
stimulation (TMS) can be used to detect brain changes in children and adolescents with major
depressive disorder. Transcranial magnetic stimulation is a noninvasive focal brain
stimulation technology which makes certain parts of the brain work without putting any wires
or chemicals into the body. Single and paired-pulse TMS involves giving one or two brief
magnetic pulses to the brain no more often than every few seconds and measuring the
subject's thumb movements. This is different from what is called repetitive transcranial
magnetic stimulation (rTMS) in which investigators rapidly give many pulses to the brain
with the idea of altering brain function and treating illnesses. This study does not involve
any treatment. It is a study to examine the brain changes associated with depression in
children and adolescents. The techniques which will be used in this study (single and
paired-pulse TMS) are much safer than rTMS and have been used safely and frequently (over
2,000 published cases) for research in children.

Investigators in this study will use TMS to measure cortical excitability (how active the
brain is) and cortical inhibition (how active the brain is and how well chemicals which slow
brain functions are working) in children and adolescents with MDD and healthy controls. The
aims of this study are to compare these measures of cortical excitability and inhibition in
these two groups (depressed children and adolescents and normal controls), and to determine
if there is a relationship between these measures of cortical inhibition and excitability
and how severe symptoms of depression are in subjects and if these measures change
differently with age in depressed children and adolescents and normal controls. The
investigators hypothesize that subjects with depression will have decreased cortical
inhibition compared to healthy controls and that depressed subjects will have greater
differences in cortical inhibition on the left and right sides of their brains than healthy
controls. The investigators also hypothesize that subjects with more severe symptoms of
depression will have lower cortical inhibition. Also it is hypothesized that, in depressed
subjects, cortical inhibition will not increase with age as significantly as it does in
healthy controls.

Inclusion Criteria:

- Children and adolescents from the ages of 8 to 17, male or female, any ethnicity.

- Major Depressive Disorder (MDD), single episode, or recurrent, moderate to severe,
based on DSM-IV-TR criteria and the Kiddie Schedule for Affective Disorders and
Schizophrenia for School Aged Children Past and Lifetime(K-SADS-PL) semi-structured
psychiatric interview by a psychiatrist, a Ph.D. level psychologist, or equivalent
professional with extensive clinical experience.

- Childhood Depression Rating Scale-Revised (CDRS-R) score of 40 or higher.

- Outpatient, inpatient, or partial hospitalization patients.

- Capable of providing informed assent (consent if age 18) in addition to consent by
parent or guardian.

- Healthy controls: will be matched for age, sex, and handedness-based on the Edinburgh
Inventory of Handedness (Oldfield 1971) to subjects with MDD. These subjects must be
in good medical and psychiatric health (no active diagnosis based on evaluation with
K-SADS-PL).

- English or Spanish Speaking

Exclusion Criteria:

- Primary Axis I or II disorder other than MDD. Any axis I or II disorder in control
subjects.

- Any psychotropic medications or any medication which could lower the subject's
seizure threshold.

- Unprovoked seizure history, seizure disorder, history of febrile seizures, family
history of epilepsy.

- Pregnancy or suspected pregnancy in females.

- Metal in the head (except the mouth), implanted medication pumps, cardiac pacemaker.

- Prior brain surgery.

- Risk for increased intracranial pressure such as a brain tumor.

- Any unstable medical condition.