We study the course of child bipolar illness and how brain function differs between youth with bipolar disorder, those 'at-risk,' and healthy volunteers.

Recently, researchers and clinicians have focused increased attention on a group of children with severe mood and behavioral dysregulation. These children are characterized by impairing symptoms that include abnormal baseline mood (i.e. irritability, anger, and/or sadness), hyperarousal (e.g. insomnia, agitation, distractibility), and increased reactivity to negative emotional stimuli. Because this syndrome shares many clinical features with bipolar disorder (BPD), there is considerable debate as to whether these children should be diagnosed with BPD. However, children with this syndrome lack the cardinal symptoms of BPD (i.e. euphoria, elation, grandiosity, decreased need for sleep, and increased goal-directed activity). Similarly, while many of these children fit diagnostic criteria for other DSM-IV diagnoses (including attention deficit hyperactivity, oppositional defiant, major depressive and/or conduct disorders), these diagnoses capture heterogeneous clinical populations that include many children who do not exhibit the symptoms noted above. Therefore, the first goal of this project is to identify reliably a group of children with severe mood and behavioral dysregulation in order to characterize them clinically and follow them longitudinally. In addition, since there are no controlled trials to guide treatment of these severely impaired children, we will conduct a double-blinded, placebo controlled trial of lithium. The goals of this trial will be to test the efficacy of lithium, and to investigate whether lithium response, which has been associated with neurotrophic effects and with changes in phosphoinositide signaling in bipolar patients, has similar effects in this group of patients. Finally we will test two preliminary hypotheses regarding the possible pathophysiology of their symptoms. To do so, we will use affect-modulated startle techniques parallel to those being used in a study of children with unequivocal BPD (Protocol #00-M-0198) as well as functional MRI.

• Mood Disorder
• Bipolar Disorder

• Biederman J, Klein RG, Pine DS, Klein DF. Resolved: mania is mistaken for ADHD in prepubertal children. J Am Acad Child Adolesc Psychiatry. 1998 Oct;37(10):1091-6; discussion 1096-9. No abstract available.
• Geller B, Williams M, Zimerman B, Frazier J, Beringer L, Warner KL. Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling. J Affect Disord. 1998 Nov;51(2):81-91.
• Carlson GA. Mania and ADHD: comorbidity or confusion. J Affect Disord. 1998 Nov;51(2):177-87. Review.

• INCLUSION CRITERIA - CHILDREN WITH SEVERE MOOD AND BEHAVIORAL DYSREGULATION (all must be met):

  1. Ages 7-17
  2. Abnormal mood (specifically anger, sadness, and/or irritability), present at least half of the day most days, and of sufficient severity to be noticeable by people in the child's environment (e.g. parents, teachers, peers).
  3. Hyperarousal, as defined by at least three of the following symptoms: insomnia, agitation, distractibility, racing thoughts or flight of ideas, pressured speech, intrusiveness.
  4. Compared to his/her peers, the child exhibits markedly increased reactivity to negative emotional stimuli that is manifested verbally or behaviorally. For example, the child responds to frustration with extended temper tantrums (inappropriate for age and/or precipitating event), verbal rages, and/or aggression toward people or property. Such events occur, on average, at least three times a week for the past four weeks.
  5. The symptoms in # 2, 3, and 4 above are currently present and have been present for at least 12 months without any symptom-free periods exceeding two months.
  6. The onset of symptoms must be prior to age 12 years.
  7. The symptoms are severe in at least one setting (e.g. violent outbursts, assaultiveness at home, school, or with peers). In addition, there are at least mild symptoms (distractibility, intrusiveness) in a second setting.
  8. For medication taper only: The child is failing his/her treatment. To meet this criterion:
• The child's current CGAS score must be less than or equal to 60.
• The child's psychiatrist/treater must agree that the child's response to his/her current treatment makes it clinically appropriate to change the child's current treatment.
• On the basis of record review and interviews with child and parent, the research team agrees that the child's response to his/her current treatment is no more than minimal (i.e. CGI-I> 2).

INCLUSION CRITERIA - CONTROLS:

Control subjects will be group matched to the patients. They will have normal physical and neurological examinations, and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology.

EXCLUSION CRITERIA - CHILDREN WITH SEVERE MOOD AND BEHAVIORAL DYSREGULATION:

1. The individual exhibits any of these cardinal bipolar symptoms:

   • Elevated or expansive mood
   • Grandiosity or inflated self-esteem
   • Decreased need for sleep
   • Increase in goal-directed activity (this can result in excessive involvement in pleasurable activities that have a high potential for painful consequences)
2. The symptoms occur in distinct periods lasting more than 4 days, and therefore meet criteria for hypomania or mania.
3. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.
4. Meets criteria for substance use disorder in the three months prior to randomization.
5. IQ less than 70.
6. The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.
7. Currently pregnant or lactating, or sexually active without using a barrier method of contraception.
8. Subjects who are ineligible for MRI scanning (e.g. braces, implanted metal devices) will be excluded from the medication-discontinuation study.

EXCLUSION CRITERIA - CONTROLS:

I.Q. less than 80; ongoing medical illness; neurologic disorder (including seizures); pregnancy; meeting past or present criteria for any diagnosis on the K-SADS-PL(7); meeting the criteria for severe mood and behavioral dysregulation; meeting criterion of post-traumatic stress disorder (exposure to a traumatic event).