Oxytocin on Irritability/Emotional Dysregulation of Disruptive Behavior and Mood Disorders
Condition: Mood Disorder; Disruptive Behavior Disorders
MeSH terms: Mood Disorders; Mental Disorders; Problem Behavior; Attention Deficit and Disruptive Behavior Disorders
Intervention: Oxytocin; Placebo
Intervention description: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.; Inactive substance administered in volume equivalent to volume administered in active treatment arm.
Intervention MeSH terms: Oxytocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 58.0
Sex: All
Minimum age: 10 Years
Maximum age: 18 Years
Healthy volunteers: No

Summary:

      Irritability and emotional dysregulation are recognized as serious aspects of psychopathology
      seen in in pediatric psychiatric patients. While various behavioral as well as
      psychopharmacological interventions have shown some efficacy in improving irritability and
      emotional dysregulation, there are no data determining the neurobiological mechanism of
      effect at the neural level. Previous studies have demonstrated that heightened amygdala
      response to negative emotional stimuli is closely related to irritability and emotional
      dysregulation in children and adolescents. Also, there are studies showing administration of
      oxytocin can decrease the heightened amygdala response to negative emotional stimuli across
      various psychiatric diagnoses. This study is a double-blind randomized trial of oxytocin for
      irritability and emotional dysregulation in the pediatric population. Neuroimaging modalities
      of fMRI and MEG are employed to probe the neuro-circuitry changes occurring as a result of
      the oxytocin intervention, specifically including heightened amygdala response to negative
      emotional stimuli and dysfunctional fronto-amygdala connectivity. The investigators will also
      investigate the genetic sequence of the oxytocin receptor in the study participants and its
      relationship with symptom profile and neural activity changes. Children and adolescents (age
      10-18) with a diagnosis of disruptive mood and/or behavior disorders (including Attention
      Deficit/Hyperactivity Disorder [ADHD], Oppositional Defiant Disorder [ODD], Conduct Disorder
      [CD], and Disruptive Mood Dysregulation Disorder [DMDD]), and clinically significant levels
      of irritability and emotional dysregulation as measured by the Affective Reactivity Index
      Scale (score>/= 4).

      2 weeks randomized, double-blind treatment with intranasal oxytocin (24 IU daily, or 12 IU
      daily if the weight is < 40kg) with assessment of diagnosis, symptom profiles (the Affective
      Reactivity Index [ARI], Inventory of Callous-Unemotional Trait [ICU], Behavior Assessment
      System for Children, second version [BASC-2], and Clinical Global Impression [CGI]) and pre-
      and post-oxytocin treatment neuroimaging (fMRI and MEG). The genetic sample will be obtained
      via buccal mucosa sampling.

      Participants may receive outpatient clinically indicated follow-up care in the UNMC
      department of psychiatry or other local community agency as appropriate.
    

Eligibility criteria:

        Inclusion Criteria:

          -  10-18 years of age

          -  A current diagnosis of ADHD, ODD, CD, or DMDD as determined by the Kiddie-SADS,
             lifetime version

          -  Clinically significant level of irritability as defined by a score of >/=4 on the
             Affective Reactivity Index (ARI) (Stringaris et al., 2012)

          -  If currently on medication, medication treatment must be stable for at least 6 weeks
             with a stimulant medication, alpha 2 agonist, atomoxetine or antidepressant.

        Exclusion Criteria:

          -  Comorbid psychotic, tic, pervasive developmental, or substance abuse disorders

          -  Major medical illness that prohibits treatment by oxytocin (e.g., severe liver
             disease, seizure disorder, metabolic disorder)

          -  Past history of significant worsening of pre-existing psychiatric symptoms after
             treatment with oxytocin

          -  Past history of allergic reaction to oxytocin and its nasal spray product

          -  History of CNS disease (including history of seizure, epilepsy, CNS tumor, CNS
             hemorrhage, or serious CNS infection including meningitis or encephalitis)

          -  Current use of antipsychotic medications and anxiolytics (benzodiazepines and
             barbiturates).

          -  A positive urine pregnancy test

          -  A positive urine drug screen or any history of or currently active diagnosis of
             substance use disorder

          -  Wechsler Abbreviated Scale of Intelligence (WASI) (D. Wechsler, 1999) scores < 70

          -  Metal in body (i.e., hearing aid, cardiac pacemaker, bone plates, braces,
             non-removable piercings/implants, etc), claustrophobia, or any other condition that
             would preclude fMRI scanning