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

Objective: Our work is driven by the core hypotheses that many of the most severe
neuropsychiatric disorders of childhood onset are associated with deviations from thepath of
normal brain development, the neuroanatomical substrates of which can be detected by magnetic
resonance imaging. Consequently, the long-term goals of the protocol are to: (1) map
neuroanatomic and neurophysiological trajectories of brain development in health and illness;
and (2) discern influences on those trajectories from demographic (e.g. age and sex),
cognitive/behavioral (e.g. IQ), and clinical (e.g. presence/absence of a known neurogenetic
disorders) factors. Data from the project have resulted in seminal papers on
Attention-Deficit/Hyperactivity Disorder, Childhood-Onset Schizophrenia, and typical
pediatric brain development. The biological bases of male / female differences are explored
via studies of subjects with anomalous sex chromosome numbers (e.g. XO, XXX, XYY, XXYY,
XXXXY).

Study population: Our studies include data from typically developing youth, and individuals
with a range of psychiatric presentations from behaviorally-defined (e.g. Childhood-Onset
Schizophrenia, Autism Spectrum Disorder) as well as geneticallydefined (e.g. Sex Chromosome
Aneuploidy) groups. Participants span a wide age range (from 3 years of age upwards).

Design: The study design is to have participants come to the NIH for brain imaging,
psychological/psychiatric testing, and genetic characterization. Assessment visits each take
approximately 2 days to complete. Participants are invited to return for longitudinal
assessments (at approximately 2-year intervals).

Outcome Measures: Primary outcome measure used to date have derived from 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. 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.

- Description of study populations:

- Participants include typically developing subjects, subjects with a variety of
neuropsychiatric conditions, and those with anomalous sex chromosome numbers or
endocrine conditions.

- The accrual ceiling is 6,000.

INCLUSION CRITERIA FOR HEALTHY CONTROLS:

Subjects 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

ADDITIONAL INCLUSION AND EXCLUSION CRITERIA FOR RETROSPECTIVE NEUROPSYCHOLOGICAL DATA
COLLECTION:

INCLUSION CRITERIA:

- At least 18 years of age

- Previous qualifications as a healthy participant

- At least 3 high quality structural MRI scans between the ages of 7 and 30 years.

Sufficient physical measures to ascertain growth during adolescence

INCLUSION CRITERIA FOR PATIENT POPULATIONS:

- Male and female subjects 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:
Multi-Dimensionally Impaired, Obsessive Compulsive Disorder, Childhood Onset
Schizophrenia, Turner Syndrome, Autism Spectrum Disorder, Asperger Syndrome, High
Functioning Autism, Pervasive Development Disorder

- Sex chromosome aneuploidy as determined by karyotype (including XXX, XXXX, XXXXX,
XXY, XXYY, XXXY, XXXXY, XYY).

- ICD-10 criteria for Congenital Adrenal Hyperplasia, Cushings Syndrome, Kallmann
Syndrome, normosmic hypogonadotropic hypogonadism, Androgen Insensitivity
Syndrome

- ADHD

- Down s Syndrome

- Newly enrolled adults and minors once they become adults over age 18 who cannot give
consent due to limited capacity may have a surrogate, i.e., a legally responsible
representative (LAR), sign the consent. LARs include DPA holders, court-appointed
legal guardians, or parents or siblings over 18 years of age. We will consult with the
Human Subjects Protection Unit as necessary.

ADDITIONAL INCLUSION CRITERIA FOR ADHD PARTICIPANTS:

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defined
ADHD. The DSM-IV diagnosis of ADHD will be based on the Parent Diagnostic Interview for
Children and Adolescents.

-Conners Teacher Hyperactivity rating greater than 2 SD above age- and sex-specific means.

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).

ADDITIONAL INCLUSION CRITERIA FOR PARTICIPANTS WITH AUTISM SPECTRUM DISORDERS:

- Meeting DSM-IV criteria for one of the pervasive developmental disorders (i.e.,
autistic disorder, Asperger disorder, or pervasive developmental disorder-not
otherwise specified).

- Having a minimum IQ of 70.

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 subject study
enrollment) in the subject, sibling, or other first-degree relative. For these
purposes, exclusionary severe psychiatric disorder include 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.

ADDITIONAL EXCLUSION CRITERIA FOR RETROSPECTIVE NEUROPSYCHOLOGICAL DATA COLLECTION:

- Presence of any psychiatric disorder in the subject.

- Current or past use of psychiatric medication.

- Presence or history of medical conditions known to affect cerebral anatomy.

EXCLUSION CRITERIA FOR ALL PATIENT POPULATIONS:

- 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.

ADDITIONAL EXCLUSION CRITERIA FOR ADHD PARTICIPANTS:

- A full-scale IQ of less than 80.

- Birth before 34 weeks of gestation.

- Other axis I psychiatric disorder requiring treatment with medication at study entry
(with the exception of oppositional-defiant disorder).