Mechanisms of Rumination Change in Adolescent Depression

Major Depressive Disorder (MDD) is a disease that has it's onset in childhood and early
adolescence for many. Treatments in adolescence tend to be acute and short-term.
Unfortunately, between half and three quarters of adolescents who have a first episode of MDD
will go to have a second episode within the next two years. Studies in adults suggest that
maintenance treatments or preventative treatments can lower these risks and delay or stop
recurrences.

The present study will use a preventative strategy, rumination-focused CBT (RF-CBT) to delay
or stop the onset of another MD episode for at least two years.

For the first 2 years of the study, adolescents with a history of MDD who are currently well
will be randomly selected for either treatment with RF-CBT or just treatment as usual in the
first two years of the study.

In the last 3 years of the study, these adolescents will be randomized to either RF-CBT or
Relaxation Therapy above and beyond TAU (Treatment as Usual). Brain, cognitive, and
self-report measurements are collected before during and after the intervention to evaluate
what brain and rumination changes occur, and which adolescents benefit the most from the
treatment.

What will happen.

1. The Investigators determine if the child is eligible (see criteria below for 14-17 year
olds with history of MDD.

2. The Investigators complete pre-intervention assessments with the child that include

1. brain imaging

2. tests of cognitive skills and emotion processing, including rumination

3. questionnaires about how the adolescent thinks and responds to situations, similar
questionnaires in at least one parent/guardian

4. measurement of sleep using a handheld wristwatch (called an actigraph - optional).

3. randomization (chance assignment) in years 1-2 to either rumination focused cognitive
behavioral therapy (RF-CBT) or assessment only for a 10-session intervention. Treatment
as usual continues for all adolescents. In years 3-5, chance assignment is to RF-CBT or
Relaxation Therapy.

4. repeat assessments after the intervention period. The cognitive skills and emotion
processing are also assessed during the middle of the intervention period.

1. brain imaging

2. tests of cognitive skills and emotion processing, including rumination

3. questionnaires about how the adolescent thinks and responds to situations, similar
questionnaires in at least one parent/guardian

4. measurement of sleep using a handheld wristwatch (called an actigraph - optional).

5. follow-up assessments to determine any changes, recurrence of depression, new treatments
for the next two years.

1. questionnaires

2. interviews

Inclusion Criteria:

- Previous diagnosis of Major Depressive Disorder (full or partial remission for at
least two weeks) according to Diagnostic and Statistical Manual (DSM-V) criteria
confirmed by the Kiddie Schedule for affective disorders (KSADSPL). Partial remission
is defined as not meeting full DSM-V criteria for MDD.

- RRS score above the age and sex specific mean, T > 50).

- 14-17 years of age at enrollment (accounting for 2 year follow-up),

- Postpubertal (Petersen Pubertal Developmental Scale)

- Youth assent and parent consent

- Intellectual Quotient (IQ) > 75, determined by Wechsler Abbreviated Scale of
Intelligence (WASI)

Exclusion Criteria:

- Endorsement of suicidality with plan or intent (assessed via KSADSPL and Children's
Depression Rating Scale (CDRS-R) clinical interviews. Current or past (within previous
three months) plan or intent is exclusionary.

- Lifetime history of conduct disorder, autism, any psychotic disorder (or episode
unexplained by other known medical causes), or bipolar disorder. Eating disorder or
alcohol/substance abuse within the previous 6 months. (Lifetime history of an anxiety
disorder, disruptive mood dysregulation disorder or oppositional defiant disorder,
Attention Deficit Hyperactivity Disorder (ADHD) will not be exclusionary).

- Current treatment with RF-CBT, Cognitive Behavioral Therapy (CBT), or variants
thereof, or in the last 2 years. Likewise, detail oriented therapy beyond supportive
therapy (e.g., homework, cognitive restructuring), in same time window (ability to
recall elements of structured therapies with CBT focus).

- Metal braces or retainers, tattoos with metal, or clothing with metal fibers.

- Claustrophobia

- Current pregnancy - Parents will be asked this information at the phone screen. At the
clinic eligibility visit, female participants will be asked about sexual activity in a
private room separate from their parents using the pregnancy script/screen that the
investigators have created. This script details that if a female is ineligible due to
pregnancy or inadequate birth control, this information will not be disclosed to her
parent(s). Participants who are sexually active will be asked about birth control
method. Abstinence will be considered an approved form of contraception.

- Psychotropic medication outside of antidepressants such as mood stabilizers and
antipsychotics will be exclusionary. Participants may have a history of current,
stable antidepressant medication use, with no changes in dose for the past four weeks,
no change in specific medication for six weeks.