N-acetylcysteine in the Treatment of Depressive Symptoms in Bipolar Offspring

To conduct an 8-week, open label study of N-acetylcysteine for the treatment of depressive
symptoms in youth at high risk for bipolar disorder, with resting state functional magnetic
resonance imaging (fMRI) examinations at baseline and endpoint. This proposal is innovative
because it investigates the efficacy and tolerability of a novel pharmacological treatment in
youth offspring of bipolar disorder, and examines the neurophysiology of predictors of mood
disorders in youth at high risk for bipolar disorder. This study will obtain pilot data to
propose a larger, neuroimaging-based, double-blind, placebo-controlled trial of
N-acetylcysteine in youth at high risk for bipolar disorder. The expected outcome, that
N-acetylcysteine will be efficacious in ameliorating depressive symptoms in youth at high
risk for bipolar disorder, and that it will demonstrate improvement in functional
connectivity within the left frontostriatal circuit associated with treatment response.

Inclusion:

1. Male or female subjects 15 years, 0 months - 24 years, 11 months of age at screening

2. For minor, at least one parent or step-parent/guardian with whom the subject lives is
willing to participate in research sessions

3. For minor, the child and relative(s) are able and willing to give written informed
assent/consent to participate, respectively

4. Subject has at least one first degree relative with Bipolar I Disorder, as assessed by
the Structured Clinical Interview for DSM (SCID) or the Kiddie Schedule for Affective
Disorders and Schizophrenia (KSADS-PL)

5. Subject shows evidence of current significant depressive symptoms as determined by a
current Hamilton Depression Rating Scale (HAM-D) greater or equal to 8

Exclusion:

1. Patient has presence of current or lifetime history of manic or hypomanic mood
episodes, psychotic disorders including schizophrenia, current major depressive
episode, and/or more than two prior major depressive episodes

2. Patient has a DSM-5 diagnosis of autism, pervasive developmental disorder, OCD, PTSD,
or Tourette's disorder

3. Patient has drug or alcohol abuse or dependence disorders in the three months prior to
study recruitment, although a lifetime history of substance or alcohol disorders can
be present if the patient has been abstinent for at least three months

4. Pregnancy; participants will be encouraged but not mandated to discuss a positive
pregnancy test with their guardians (if minors) and we will follow local laws

5. Patient has history of major neurological disorders (such as epilepsy), or head trauma
with > 10 minutes loss of consciousness

6. Patient has evidence of mental retardation (IQ less than 70), as determined by the
Wechsler Abbreviated Scale of Intelligence (WASI)

7. Patient has any contraindication for MRI, including metal in the body related to an
injury or surgery (e.g., surgical clips, metal fragments in the eyes), piercings that
cannot be removed, or braces

8. Patient has history of allergic reaction to N-acetylcysteine