Clinical trial NCT02415647: Longitudinal Family/Molecular Genetic Study to Validate Research Domain Criteria
Official title: Longitudinal Family/Molecular Genetic Study to Validate Research Domain Criteria
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mental Disorders
Psychological Disorders
Psychiatric, Diagnosis
Mental Disorders Diagnosed in Childhood
Keywords: children
mental health
family genetic study
Lead sponsor: State University of New York - Upstate Medical University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2015-04-14
Enrollment: 2806
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Child probands with psychiatric disorders will be recruited from psychiatric clinics, child psychiatrists, and mental health providers in Onondaga County. Non-disordered psychiatrially normal comparison groups will be recruited from a pediatric primary care clinic.

Brief summary: The purpose of this research is to study new ways of classifying mental disorders in children based on observable behavior and genetics to ultimately diagnose these disorders better.

Detailed description: The NIMH Research Domain Criteria (RDoC) initiative seeks to further a long-range goal of contributing to diagnostic systems as informed by research on genetics, neuroscience, and behavior. The RDoC approach is based on identifying the most elemental units of analysis relevant to psychiatric disorders (such as genes and molecules) and using this matrix as a framework for investigation. In this case-control family study, the investigators will be using self-report questionnaires and computer-based tests to develop diagnostic methods for neuropsychiatric disorders in children, their siblings, and their parents. They will do this by recruiting "normal" and "affected" children, their siblings, and their parents. They will look at the subject, sibling, and parents to determine if psychiatric disorders are inherited. "Affected" children, ages 6-12, are those who have been diagnosed with a psychiatric disorder. Participants will undergo a battery of questionnaires/evaluations and a blood draw. The investigators will determine if the questionnaires and tests that reflect the constructs (such as reward prediction and willingness to work) predict psychopathology and impairment. The blood draw will be genotyped to determine if the measured constructs are associated with neuropsychiatric candidate genes, cross-disorder candidate gens and a cross-disorder polygenic score.

Eligibility criteria: Inclusion Criteria:

* male or female, ages 6-12.
* biological child of parent(s) participating in testing.

Exclusion Criteria:

* taking psychotropic medications.
* free of uncontrolled medical problems.
* major sensorimotor disability (e.g., deafness, blindness).
* diagnosed neurological condition.
* inadequate command of the English language.
* history of head injury with loss of consciousness lasting longer than 10 minutes.
* IQ estimated at below 80.

Primary outcomes:
measure: Reward Valuation
timeFrame: Baseline
measure: Effort Valuation/Willingness to Work
timeFrame: Baseline
measure: Expectancy/Reward Prediction Error
timeFrame: Baseline
measure: Initial Responsiveness to Reward Attainment
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Syracuse
country: United States
facility: Upstate Medical University
state: New York
Study officials:
affiliation: Upstate Medical University
name: Stephen Faraone, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Glatt SJ, Stone WS, Faraone SV, Seidman LJ, Tsuang MT. Psychopathology, personality traits and social development of young first-degree relatives of patients with schizophrenia. Br J Psychiatry. 2006 Oct;189:337-45. doi: 10.1192/bjp.bp.105.016998.
citation: Faraone SV, Seidman LJ, Kremen WS, Kennedy D, Makris N, Caviness VS, Goldstein J, Tsuang MT. Structural brain abnormalities among relatives of patients with schizophrenia: implications for linkage studies. Schizophr Res. 2003 Apr 1;60(2-3):125-40. doi: 10.1016/s0920-9964(02)00304-3.
citation: Faraone SV, Su J, Tsuang MT. A genome-wide scan of symptom dimensions in bipolar disorder pedigrees of adult probands. J Affect Disord. 2004 Oct;82 Suppl 1:S71-8. doi: 10.1016/j.jad.2004.05.015.
citation: Glatt SJ, Su JA, Zhu SC, Zhang R, Zhang B, Li J, Yuan X, Li J, Lyons MJ, Faraone SV, Tsuang MT. Genome-wide linkage analysis of heroin dependence in Han Chinese: results from wave one of a multi-stage study. Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):648-52. doi: 10.1002/ajmg.b.30361.
citation: Glatt SJ, Faraone SV, Lasky-Su JA, Kanazawa T, Hwu HG, Tsuang MT. Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan. Mol Psychiatry. 2009 Sep;14(9):885-93. doi: 10.1038/mp.2008.30. Epub 2008 Mar 11.
citation: Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013 Apr 20;381(9875):1371-1379. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28.
citation: Faraone SV, Matise T, Svrakic D, Pepple J, Malaspina D, Suarez B, Hampe C, Zambuto CT, Schmitt K, Meyer J, Markel P, Lee H, Harkavy Friedman J, Kaufmann C, Cloninger CR, Tsuang MT. Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium. Am J Med Genet. 1998 Jul 10;81(4):290-5.
citation: Faraone SV, Biederman J, Mick E, Wozniak J, Kiely K, Guite J, Ablon JS, Warburton R, Reed E. Attention deficit hyperactivity disorder in a multigenerational pedigree. Biol Psychiatry. 1996 May 15;39(10):906-8. doi: 10.1016/0006-3223(95)00194-8. No abstract available.
citation: Faraone SV, Adamson JJ, Wilens TE, Monuteaux MC, Biederman J. Deriving phenotypes for molecular genetic studies of substance use disorders: a family study approach. Drug Alcohol Depend. 2007 May 11;88(2-3):244-50. doi: 10.1016/j.drugalcdep.2006.11.002. Epub 2006 Dec 1.
citation: Faraone SV, Adamson JJ, Wilens TE, Monuteaux MC, Biederman J. Familial transmission of derived phenotypes for molecular genetic studies of substance use disorders. Drug Alcohol Depend. 2008 Jan 1;92(1-3):100-7. doi: 10.1016/j.drugalcdep.2007.07.002. Epub 2007 Sep 4.