Genetic Aspects of Neurologic and Psychiatric Disorders

The purpose of this study is to improve the understanding of the genetic causes of specific neurologic and psychiatric disorders. The study will focus on conditions of mental retardation, childhood onset schizophrenia, attention deficit hyperactivity disorder (ADHD), atypical psychosis of childhood, and bipolar affective disorder.

The study addresses the belief that there may be several genes contributing to the illness. Researchers intend to use several molecular genetic techniques in order to identify the areas of chromosomes containing genes responsible for the development of these disorders.

Patients will be selected to participate in this study based on an early age of onset of their condition as well as the severity of the illness and the frequency of the illness among family members. Researchers will collect DNA samples from patients as well as affected and unaffected family members of each patient. The DNA samples collected will be analyzed for a variety of genetic abnormalities including; triplet repeat expansions, chromosome rearrangements, and polymorphisms.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Bipolar Disorder; Attention Deficit Disorder With Hyperactivity; Mental Retardation; Mental Disorder Diagnosed in Childhood

Detailed Description

We propose to use DNA probes to study patients having specific neurologic and psychiatric disorders, especially focusing on patients with early onset or extreme phenotypes such as childhood onset schizophrenia (COS), mental retardation (MR), attention deficit hyperactivity disorder (ADHD), atypical psychosis of childhood, (multi-dimensional impairment MDI), and bipolar affective disorder (BPAD). This study addresses the hypothesis that genetic risk factors contribute to these diverse phenotypes. Several complementary molecular genetic techniques are employed to identify chromosomal regions containing genes contributing to specific neurologic and psychiatric disorders. Patients will be selected for this study on the basis of the age of onset and severity of neurologic or psychiatric symptoms, familial genetic loading and family structure. Individuals participating in this protocol will be clinically evaluated through other NIMH or NIH clinical protocols, particularly through those of the Child Psychiatry Branch (reference protocol numbers 85-M-0115, 84-M-0050, 97-M-0126). Those subjects meeting inclusion criteria may undergo a screening that may include physical, neurologic or psychiatric examinations. As appropriate, this initial screen may be followed by more formal, structured instruments such as the Schedule for Affective Disorders (SADS), the revised Weschler Adult Intelligence Scale (WAIS-R), the Conner's revised parent and teacher ratings, and the Diagnostic Interview for Children and Adolescents (DICA- version IV) to confirm the clinical diagnosis at the discretion of the treating physician. Venipuncture and/or buccal swabs will be performed in order to obtain samples for DNA extraction or to establish a lymphoblast cell line to be used in genetic tests. Samples will also be collected from family members and controls for these studies.

• Study Type: Observational
• Enrollment: 1227

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Mental Health (NIMH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

Individuals with selected psychiatric and neurologic disorders, including childhood onset schizophrenia, atypical psychosis, mental retardation, bipolar affective disorder, and ADHD.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute of Mental Health (NIMH)

Publications and helpful links

General Publications

• Willems PJ. Dynamic mutations hit double figures. Nat Genet. 1994 Nov;8(3):213-5. doi: 10.1038/ng1194-213. No abstract available.
• Koide R, Ikeuchi T, Onodera O, Tanaka H, Igarashi S, Endo K, Takahashi H, Kondo R, Ishikawa A, Hayashi T, et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet. 1994 Jan;6(1):9-13. doi: 10.1038/ng0194-9.
• Philibert RA, Hawkins GA, Damschroder-Williams P, Stubblefield BK, Martin BM, Ginns EI. Direct sequencing of trinucleotide repeats from cosmid genomic DNA template. Anal Biochem. 1995 Mar 1;225(2):372-4. doi: 10.1006/abio.1995.1174. No abstract available.

Study record dates

Study Major Dates

• Study Start: April 1, 1996
• Study Completion: March 1, 2004

Study Registration Dates

• First Submitted: November 3, 1999
• First Submitted That Met QC Criteria: November 3, 1999
• First Posted (Estimate): November 4, 1999

Study Record Updates

• Last Update Posted (Estimate): March 4, 2008
• Last Update Submitted That Met QC Criteria: March 3, 2008
• Last Verified: March 1, 2004

More Information

Terms related to this study

• Keywords: Schizophrenia; Mental Retardation; Genotyping; Family Studies; DNA Probes; Trinucleotide Repeats; Lymphoblast Cell Lines; Bipolar Affective Disorders; Neuropsychiatric Disorders
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Attention Deficit and Disruptive Behavior Disorders; Schizophrenia; Disease; Problem Behavior; Mental Disorders; Bipolar Disorder; Attention Deficit Disorder with Hyperactivity; Intellectual Disability; Neurodevelopmental Disorders
• Other Study ID Numbers: 960060; 96-M-0060