Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Volunteers

Study Description:

This natural history protocol will have participants come to the NIH for brain imaging, psychological/psychiatric testing, and genetic characterization. Our core hypotheses are that many of the most severe neuropsychiatric disorders of childhood onset are associated with deviations from the path of normal brain development, the neuroanatomical substrates of which can be detected by magnetic resonance imaging.

Objectives:

Primary Objectives:

The long-term objectives of the protocol are to (1) map the neuroanatomic and neurophysiological trajectories of brain development; and (2) discern the influences, for good or ill, on those trajectories from demographic clinical, genetic, and environmental factors. Approximately half of the participants in our sample are typically developing. Clinical populations in our sample include participants with a variety of brain-based disorders, such as Autism, Attention-Deficit/Hyperactivity Disorder, Childhood Onset Schizophrenia, Dyslexia, Sydenham s Chorea, and Tourette s Syndrome.

Secondary Objectives:

To characterize the relationships among measures of behavior and cognition as well as amongst multimodal measures of brain organization.

Endpoints:

Primary Endpoint:

T1-weighted structural neuroimaging data which enable us to characterize how a range of anatomical brain phenotypes vary as a function of age, sex, behavioral/cognitive traits, diagnostic status and genotype.

Secondary Endpoints:

Data analyses also consider how these factors relate to other outcomes of interest including; gene expression levels, functional metrics from in vivo neuroimaging, and questionnaire/interview-based assessment of clinical features.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Inclusion criteria

for healthy controls

Participants consenting to participation in the study

-Over 3 years of age with no upper limit for age at time of enrollment.

Inclusion criteria

for MRI scanner calibration project:

Participants will meet protocol criteria for adult healthy volunteers.

Inclusion criteria

for affected participant populations:

-Male and female participants over 3 years of age with no upper limit for age (with the exception of the Down syndrome group - see below). Currently meet criteria for at least one of the following:

• DSM-IV (or other approved) criteria for one of the following clinical diagnoses: Obsessive Compulsive Disorder, Childhood Onset Schizophrenia, Turner Syndrome, Autism Spectrum Disorder, Asperger Syndrome, High Functioning Autism, Pervasive Development Disorder
• ICD-10 criteria for Congenital Adrenal Hyperplasia, Cushings Syndrome, Kallmann Syndrome, Androgen Insensitivity Syndrome.
• ADHD
• Chromosomal aneuploidies including Down s Syndrome and Sex chromosome aneuploidy as determined by karyotype (including XXX, XXXX, XXXXX, XXY, XXYY, XXXY, XXXXY, XYY, and XO).

Additional Inclusion criteria for Down Syndrome participants:

• Confirmed chromosomal diagnosis of Down syndrome.
• Age at entry into the study is 30 years or under. This upper age limit at study entry is being implemented for the Down syndrome group for several reasons. First, much of the research using magnetic resonance imaging with this population is focused on (older) adult populations and in particular the transition to early onset Alzheimer s disease. Because most (if not all) individuals with Down syndrome demonstrate some brain pathology consistent with Alzheimer s disease by age 30 (e.g., plaques and tangles; Mann & Esiri, 1989), we would like to enroll participants who are 30 years of age and under. Second, studying children and young adults with Down syndrome fills a significant gap in the literature, as there are very few structural magnetic resonance imaging studies of children and young adults with Down syndrome reported in the literature to date, and the majority of these studies are characterized by small samples of convenience (i.e., clinic populations). Thus, there is still a need to describe the developmental course of this disorder from early childhood to young adulthood. Such developmental research may help shed light on the causes of intellectual disability in Down syndrome and also identify individuals with the syndrome who are most at risk for experiencing the cognitive decline that is reported in the literature for some individuals after the age of 30 (Oliver et al., 1998).

Inclusion criteria

for parents and siblings of affected participant populations:

Participants consenting to participation in the study

• Over 3 years of age with no upper limit for age at time of enrollment.
• Parents must have the ability to understand and provide informed consent to the study.

Exclusion criteria

NIMH staff and their immediate family are excluded from participation.

Exclusion criteria

for healthy controls:

• Presence of severe psychiatric disorder (as diagnosed prior to participant study enrollment) in the participant. For these purposes, exclusionary severe psychiatric disorder includes schizophrenia and bipolar affective disorder.
• Presence or history of medical conditions known to affect cerebral anatomy.
• Dental braces.
• Contraindications for MRI scanning according to the NMR Center MRI Safety Screening Questionnaire and guidelines.
• For females who have reached menarche: Pregnancy or inability or unwillingness to undergo pregnancy testing.

Exclusion criteria

for all affected participant populations, including parents and siblings of the affected participants:

• Dental braces.
• Contraindications for MRI scanning according to the NMR Center MRI Safety Screening Questionnaire and guidelines.
• For females who have reached menarche: Pregnancy or inability or unwillingness to undergo pregnancy testing.
• Evidence of another medical condition or traumatic event known to affect cerebral anatomy.
• A known genetic disorder (other than the condition under investigation) that would be expected to significantly impact findings from cognitive testing and/or neuroimaging.