- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00001246
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....
Study Overview
Status
Detailed Description
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 the path 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 genetically-defined (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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Jonathan Blumenthal
- Phone Number: (301) 435-4516
- Email: jonathan.blumenthal@nih.gov
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- Recruiting
- National Institutes of Health Clinical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
- 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: 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, 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 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 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).
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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1
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 genetically-defined (e.g.
Sex Chromosome Aneuploidy) groups.
Participants span a wide age range (from 3 years of age upwards).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Volumetric MRI Data
Time Frame: Ongoing
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Volumetric MRI Data
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Ongoing
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Secondary Outcome Measures
Outcome Measure |
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Cognitive data
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Collaborators and Investigators
Investigators
- Principal Investigator: Armin Raznahan, M.D., National Institute of Mental Health (NIMH)
Publications and helpful links
General Publications
- Csumitta KD, Gotts SJ, Clasen LS, Martin A, Raitano Lee N. Youth with Down syndrome display widespread increased functional connectivity during rest. Sci Rep. 2022 Jun 14;12(1):9836. doi: 10.1038/s41598-022-13437-1.
- Lee NR, Niu X, Zhang F, Clasen LS, Kozel BA, Smith ACM, Wallace GL, Raznahan A. Variegation of autism related traits across seven neurogenetic disorders. Transl Psychiatry. 2022 Apr 7;12(1):149. doi: 10.1038/s41398-022-01895-0.
- Mankiw C, Whitman ET, Torres E, Lalonde F, Clasen LS, Blumenthal JD, Chakravarty MM, Raznahan A. Sex-specific associations between subcortical morphometry in childhood and adult alcohol consumption: A 17-year follow-up study. Neuroimage Clin. 2021;31:102771. doi: 10.1016/j.nicl.2021.102771. Epub 2021 Jul 26.
- Warling A, Yavi M, Clasen LS, Blumenthal JD, Lalonde FM, Raznahan A, Liu S. Sex Chromosome Dosage Effects on White Matter Structure in the Human Brain. Cereb Cortex. 2021 Oct 22;31(12):5339-5353. doi: 10.1093/cercor/bhab162.
- Whitman ET, Liu S, Torres E, Warling A, Wilson K, Nadig A, McDermott C, Clasen LS, Blumenthal JD, Lalonde FM, Gotts SJ, Martin A, Raznahan A. Resting-State Functional Connectivity and Psychopathology in Klinefelter Syndrome (47, XXY). Cereb Cortex. 2021 Jul 29;31(9):4180-4190. doi: 10.1093/cercor/bhab077.
- Wilson KE, Fish AM, Mankiw C, Xenophontos A, Warling A, Whitman E, Clasen L, Torres E, Blumenthal J, Raznahan A. Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome. J Neurodev Disord. 2021 Mar 22;13(1):12. doi: 10.1186/s11689-021-09360-7.
- Schmitt JE, Raznahan A, Liu S, Neale MC. The Heritability of Cortical Folding: Evidence from the Human Connectome Project. Cereb Cortex. 2021 Jan 1;31(1):702-715. doi: 10.1093/cercor/bhaa254.
- Liu S, Seidlitz J, Blumenthal JD, Clasen LS, Raznahan A. Integrative structural, functional, and transcriptomic analyses of sex-biased brain organization in humans. Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18788-18798. doi: 10.1073/pnas.1919091117. Epub 2020 Jul 20.
- Raznahan A. Editorial: Do Different Neurogenetic Disorders Impart Different Profiles of Psychiatric Risk? J Am Acad Child Adolesc Psychiatry. 2020 Sep;59(9):1022-1024. doi: 10.1016/j.jaac.2020.03.002. Epub 2020 Apr 12.
- Dworkin JD, Linn KA, Solomon AJ, Satterthwaite TD, Raznahan A, Bakshi R, Shinohara RT. A local group differences test for subject-level multivariate density neuroimaging outcomes. Biostatistics. 2021 Jul 17;22(3):646-661. doi: 10.1093/biostatistics/kxz058.
- Xenophontos A, Seidlitz J, Liu S, Clasen LS, Blumenthal JD, Giedd JN, Alexander-Bloch A, Raznahan A. Altered Sex Chromosome Dosage Induces Coordinated Shifts in Cortical Anatomy and Anatomical Covariance. Cereb Cortex. 2020 Apr 14;30(4):2215-2228. doi: 10.1093/cercor/bhz235.
- Schmitt JE, Raznahan A, Clasen LS, Wallace GL, Pritikin JN, Lee NR, Giedd JN, Neale MC. The Dynamic Associations Between Cortical Thickness and General Intelligence are Genetically Mediated. Cereb Cortex. 2019 Dec 17;29(11):4743-4752. doi: 10.1093/cercor/bhz007.
- Nadig A, Reardon PK, Seidlitz J, McDermott CL, Blumenthal JD, Clasen LS, Lalonde F, Lerch JP, Chakravarty MM, Raznahan A. Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures. eNeuro. 2018 Nov 29;5(5):ENEURO.0265-18.2018. doi: 10.1523/ENEURO.0265-18.2018. eCollection 2018 Sep-Oct. Erratum In: eNeuro. 2019 Feb 14;6(1):
- McDermott CL, Seidlitz J, Nadig A, Liu S, Clasen LS, Blumenthal JD, Reardon PK, Lalonde F, Greenstein D, Patel R, Chakravarty MM, Lerch JP, Raznahan A. Longitudinally Mapping Childhood Socioeconomic Status Associations with Cortical and Subcortical Morphology. J Neurosci. 2019 Feb 20;39(8):1365-1373. doi: 10.1523/JNEUROSCI.1808-18.2018. Epub 2018 Dec 26.
- Joseph L, Farmer C, Chlebowski C, Henry L, Fish A, Mankiw C, Xenophontos A, Clasen L, Sauls B, Seidlitz J, Blumenthal J, Torres E, Thurm A, Raznahan A. Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome. J Neurodev Disord. 2018 Oct 22;10(1):30. doi: 10.1186/s11689-018-9248-7.
- Hamner T, Udhnani MD, Osipowicz KZ, Lee NR. Pediatric Brain Development in Down Syndrome: A Field in Its Infancy. J Int Neuropsychol Soc. 2018 Oct;24(9):966-976. doi: 10.1017/S1355617718000206. Epub 2018 May 23.
- Lenroot RK, Blumenthal JD, Wallace GL, Clasen LS, Lee NR, Giedd JN. A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome. Genes Brain Behav. 2014 Nov;13(8):841-9. doi: 10.1111/gbb.12180. Epub 2014 Oct 27.
- Nadig A, Seidlitz J, McDermott CL, Liu S, Bethlehem R, Moore TM, Mallard TT, Clasen LS, Blumenthal JD, Lalonde F, Gur RC, Gur RE, Bullmore ET, Satterthwaite TD, Raznahan A. Morphological integration of the human brain across adolescence and adulthood. Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):e2023860118. doi: 10.1073/pnas.2023860118.
- Raznahan A, Disteche CM. X-chromosome regulation and sex differences in brain anatomy. Neurosci Biobehav Rev. 2021 Jan;120:28-47. doi: 10.1016/j.neubiorev.2020.10.024. Epub 2020 Nov 7.
- Bedford SA, Park MTM, Devenyi GA, Tullo S, Germann J, Patel R, Anagnostou E, Baron-Cohen S, Bullmore ET, Chura LR, Craig MC, Ecker C, Floris DL, Holt RJ, Lenroot R, Lerch JP, Lombardo MV, Murphy DGM, Raznahan A, Ruigrok ANV, Smith E, Spencer MD, Suckling J, Taylor MJ, Thurm A; MRC AIMS Consortium; Lai MC, Chakravarty MM. Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder. Mol Psychiatry. 2020 Mar;25(3):614-628. doi: 10.1038/s41380-019-0420-6. Epub 2019 Apr 26.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Nervous System Diseases
- Neurologic Manifestations
- Schizophrenia Spectrum and Other Psychotic Disorders
- Dyskinesias
- Attention Deficit and Disruptive Behavior Disorders
- Neurodevelopmental Disorders
- Schizophrenia
- Problem Behavior
- Mental Disorders
- Attention Deficit Disorder with Hyperactivity
- Hyperkinesis
- Endocrine System Diseases
Other Study ID Numbers
- 890006
- 89-M-0006
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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