Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Volunteers
Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Volunteers
Magnetic Resonance Imaging (MRI) unlike X-rays and CT-scans does not use radiation to create
 a picture. MRI use as the name implies, magnetism to create pictures with excellent
 anatomical resolution. Functional MRIs are diagnostic tests that allow doctors to not only
 view anatomy, but physiology and function. It is for these reasons that MRIs are excellent
 methods for studying the brain.

 In this study, researchers will use MRI to assess brain anatomy and function in X and Y
 chromosome variation, healthy volunteers, and patients with a variety of childhood onset
 psychiatric disorders. The disorders include attention deficit disorder, autism, congenital
 adrenal hyperplasia, childhood-onset schizophrenia, dyslexia, obsessive compulsive disorder,
 Sydenham's chorea, and Tourette's syndrome.

 Results of the MRIs showing the anatomy of the brain and brain function will be compared
 across age, sex (gender), and diagnostic groups. Correlations between brain and behavioral
 measures will be examined for normal and clinical populations....
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.
-  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

 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.

 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).