The National Institute of Mental Health is seeking boys and girls ages 6 to 17 with bipolar disorder who are not doing well on their current medication(s) to participate in a research study. The study includes outpatient assessment, full or partial hospitalization, discontinuation of all current medications, fMRI scanning (a form of brain imaging), and starting new medications at the NIH Clinical Center in Bethesda, MD. No novel or experimental treatments are part of this study. Participants will receive a thorough clinical evaluation.

Participants must be:

In treatment for bipolar disorder with a psychiatrist who agrees that it is appropriate for the child to participate in the study

Psychiatrically unstable on current medications

Able to fill out daily self rating forms and cooperate with study procedures (includes genetics study, MRI, neuropsychological and behavioral testing, and others)

Bipolar disorder (BPD) in children and adolescents is receiving increased research attention, but important questions remain about its phenomenology and about underlying neural mechanisms. This study has two specific aims: 1) to use longitudinal, objective techniques to characterize the clinical manifestations of early-onset bipolar illness, and to obtain genetic and family data; and 2) to identify behavioral, neuropsychological and neurophysiological correlates of affective dysregulation in bipolar children and adolescents. To accomplish Specific Aim #1, we will obtain prospective clinical data, following patients longitudinally (clinically and with structural MRI scans) for 4 years. In addition, we will assess the psychiatric status of family members, and bank genetic samples from patients and first-degree relatives for use in future studies. To accomplish Specific Aim #2, we will use standardized emotional stimuli to test the hypothesis that responses to negative emotional stimuli are more pronounced in children with BPD than in controls. In addition, we will test the hypotheses that, relative to controls and to children with other psychopathology, children with BPD have distinct deficits in reward systems and in social information processing. Finally, we hypothesize that children who are at risk for BPD will have deficits similar to those exhibited by children with BPD.

• Healthy
• Bipolar Disorder

• Geller B, Sun K, Zimerman B, Luby J, Frazier J, Williams M. Complex and rapid-cycling in bipolar children and adolescents: a preliminary study. J Affect Disord. 1995 Aug 18;34(4):259-68.
• Wozniak J, Biederman J, Kiely K, Ablon JS, Faraone SV, Mundy E, Mennin D. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry. 1995 Jul;34(7):867-76.
• Faedda GL, Baldessarini RJ, Suppes T, Tondo L, Becker I, Lipschitz DS. Pediatric-onset bipolar disorder: a neglected clinical and public health problem. Harv Rev Psychiatry. 1995 Nov-Dec;3(4):171-95. Review.

• INCLUSION AND EXCLUSION CRITERIA

INCLUSION CRITERIA:

Bipolar patients: Boys and girls must be ages 6-17 and meet DSM-IV criteria for bipolar disorder. The child must have a primary caregiver who can accompany him or her on trips to NIMH, provide reliable history and information, and complete daily rating scales and sleep logs. Patients must have a psychiatrist who provides clinical care for their BPD. All youth accepted into the study must be able to complete self-rating forms and to cooperate with other study procedures. Subjects must be on a stable medication regimen for at least 14 days prior to enrollment in the study. In addition, they, their parents, and treating physician must agree to keep medications stable (with the exception of minor dosage adjustments) until the end of the second NIMH evaluation, if clinically feasible and acceptable. The total duration of the medication-stable period will be approximately six weeks.

Controls: Control subjects will be age-and sex-matched to the patients. They will have no significantly abnormal physical and neurological examinations by history, and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology.

Children with ADHD: Children with ADHD will be: age 7-17, currently meets DSM-IV criteria for ADHD (this will be determined by a K-SADS interview), tscore greater than 65 on the Connors Teacher and the Connors Parent scales, and in treatment for the illness with a physician. Exclusion criteria will be IQ less than 80; pregnancy; medical illness or neurological disorder other than ADHD; contraindication to discontinuing medication for 72 hours; contraindication to fMRI scanning; any other psychiatric disorder that is sufficiently severe to require specific treatment, with the exception of oppositional defiant disorder, and the learning, communication, and elimination disorders.

Children with BPD for Discontinuation of Medication with fMRI: Individuals will meet criteria for BPD, as above. The criteria for treatment failure will be: 1) the child's current CGAS score is less than or equal to 60, and 2) the child's psychiatrist agrees that a change in medication regimen is jusified clinically.

Children at Risk for BPD: Children age 3-17 with a parent or a sibling diagnosed with BPD.

Parents of healthy volunteer children: Parents, age 25-65

Adult Bipolar adults for fMRI only, or as parents of at risk children: Adult Bipolar Patients will meet inclusion criteria based on their ability to participate in fMRI scanning safely and their eligibility for protocols 80-M-0083, and for other protocols in MAP that are recruiting bipolar adults (including 02-M-0018, 37, 85, 92. 176, and others), as indicated below.

Extended Relatives of At-Risk Parents/Children: Inclusion criteria will include individuals age 7-65 who are first, second, or third degree relatives of patients with bipolar disorder or of individuals at risk for bipolar disorder.

EXCLUSION CRITERIA

Bipolar patients: I.Q. less than 70; autistic disorder or severe pervasive development disorder; psychosis that interferes with the child's capacity to understand and comply with study procedures; unstable medical illness (e.g. severe asthma); medical illness that could cause the symptoms of bipolar illness (e.g. multiple sclerosis, thyroid disease); pregnancy; or substance abuse within two months of the initial evaluation.

Controls: I.Q. less than 70; ongoing medical illness; neurological disorder (including seizures); pregnancy; past or present substance abuse; history of sexual abuse.

Discontinuation of Medication with fMRI: In addition to exclusion criteria for Bipolar patients, the presence of dental braces or extreme separation anxiety.

Parents of healthy volunteer children: IQ less than 70; ongoing medical illness; neurological disorder (including seizures); pregnancy; past or present substance abuse; history of sexual abuse, history of specific Axis I psychiatric disorders.

Extended Relatives of At-Risk Parents/Children: Exclusion criteria will include: (1) active psychosis, (2) dementia, (3) IQ less than 70, (4) any clinical condition in need of immediate care, (5) any chromic medical illness resulting in impaired CNS function, or (6) any condition that would interfere with the participants' ability to perform the research tasks.