Resilience in Adolescent Development

The primary objective of this initiative is to implement a prospective study that will allow
the investigators to identify and validate biosignatures of resilience. Specifically, the
research will identify protective factors (socio-demographic, lifestyle, clinical and
behavioral assessments, fluid-based biomarkers, genomics, neuroimaging, EEG and cell-based
assays) that reduce risk of developing mood and anxiety disorders in adolescents and young
adults at risk for these illnesses.

Presence and severity of symptoms will be assessed over 10 years using questionnaires for
symptom changes, social factors, and overall quality of life. Other outcomes generated from
this study will include rate of change in quantitative measures of brain function, of
depression relevant brain regions correlated with systems-levels behavior and other
functional neuro-circuitry MRI measures. Rate of change of specified biochemical biomarkers
will also be assessed.

Integration of these measures will provide an unmatched understanding into the mechanisms of
resilience and protection against depression and anxiety disorders, and holds tremendous
promise for identifying targets for prevention strategies.

Specific Aims:

Aim 1 Examine baseline biosignatures and independent factors (demographic, social,
environmental, genetic, EEG, and fMRI) associated with resilience in at-risk adolescents and
young adults.

Aim 2 Examine changes in the biomarker factors annually for 10 years to determine for
plasticity of these biomarkers.

Aim 3 Examine the interaction between psychiatric symptoms and changes in the biopsychosocial
signature.

The following variables will be evaluated:

Based on this, the investigators determined that the most promising variables to evaluate
are:

1. Comprehensive clinical phenotype;

2. Magnetic resonance imaging using MRI measures of cortical structure;

3. Diffusion tensor imaging (DTI) to assess cortical white matter tract integrity;

4. Functional magnetic resonance imaging (fMRI) using multiple tasks to assess brain
activation patterns to both emotional conflict and reward-dependent learning tasks;

5. Quantitative electroencephalography (EEG) to assess cortical and subcortical brain
activation patterns, using advanced EEG processing techniques;

6. Cortical evoked EEG potentials;

7. Behavioral neuropsychological tasks to include reaction time, and motor processing
speed;

8. DNA, mRNA, and plasma, urine and saliva protein and metabolomics samples, collected at
baseline and throughout the study

9. Socio-economic, demographic and life habits parameters.

Planned analyses include: Assessment of individual moderators/mediators: The first set of
analyses will test an a priori list of individual variables for status as moderators and
mediators. Depression symptom change from baseline will be measured using the Inventory of
Depressive Symptomatology-Clinician (IDS-C). Tolerability will be measured using the
Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) and the Treatment Emergent
Symptom Scale (TESS). Other measures (i.e., treatment response, remission) may also be used
and correlated variables collected in the study.

Inclusion Criteria:

- Adolescents and young adults aged 10-24, male and female of all races and ethnicity.

- Participants must be English-speaking (because several study assessments are only
available in the English language), however the parent(s) or legal guardian may either
speak English or Spanish as the consenting process can be conducted bilingually.

- Adults age 18 and older must be able to provide written informed consent; for youth
younger than age 18, a parent or legal guardian must provide written informed consent,
and the child or teen must provide written informed assent.

- Ability to complete clinical evaluations and neuropsychological testing.

Exclusion Criteria:

- Individuals who are unable to provide informed consent.

- Participants who are non-English speaking.

- Individuals with any of the following psychotic features: MDD with psychotic features,
schizophrenia, schizoaffective disorder, or other Axis I psychotic disorder.

- Individuals with a depression diagnosis or a history of depression diagnosis at the
initial visit (participants who develop depression during the longitudinal follow-up
will continue in the study).

- A PHQ-9 score of 10 or greater.

- Individuals who are unable to provide a permanent home address and contact
information.

- Individuals with any condition for which, in the opinion of the investigator, study
participation would not be in their best interest (e.g., compromise their well-being)
or that could prevent, limit, or confound the protocol-specified assessments.