Genetic Study of Schizophrenia

Objective: Schizophrenia is a complex genetic disorder which likely involves many genes each
producing a slight increase in risk. Finding weak-acting genes in complex genetic disorders
has been challenging and will likely require a number of approaches and large clinical
samples. Several strategies have emerged recently that appear to markedly improve the power
of genetic studies for detecting such genes. These include using association (rather than
linkage) and using intermediate phenotypes in addition to DMS-IV diagnosis.

Study Population: We propose to take advantage of these techniques by studying quantitative
traits related to schizophrenia in patients, siblings, and controls.

Design: We will employ an association design, rather than linkage. Traits will include
quantifiable neurobiological variables that have been implicated previously as possible
phenotypes related to schizophrenia. These include tests of attention and cognition, and a
variety of parameters using brain imaging and magnetoencephalography.

Outcome Measure: We will use several statistical methods to show that specific genetic
polymorphisms affect these phenotypes, including case control and family based association
studies.

- INCLUSION/EXCLUSION CRITERIA:

Inclusion criteria for Siblings (probands and unaffected siblings):

- Probands must have a DSM IV-R diagnosis of schizophrenia,schizoaffective disorder,
psychosis N.O.S. or schizophreniform disorder.

- Probands and Siblings must be between the ages of 18 and 55

- Probands and Siblings must be free of major medical illnesses, but may have controlled
hypertension, thyroid disease, or diabetes.

- Probands and Siblings who do not have capacity to provide consent and are under
guardianship can participate in the study if the guardian signs the informed consent
and the research subject provides their written assent. A DPA is not utilized in this
study.

- Fluency in English is required.

Exclusion Criteria for Siblings (probands and unaffected siblings):

- Seizure disorder, mental retardation, organic brain damage or other neurological
disease.

- History of any (excepting nicotine-related) DSM5-defined moderate to severe substance
use disorder (or DSM-IV-defined substance dependence).

- Cumulative lifetime history of any (excepting nicotine-related) DSM5-defined mild
substance use disorder (or any DSM-IV-defined substance abuse), either in excess of 5
years total or not in remission for at least 6 months.

- Head trauma with loss of consciousness over 5 minutes from all but genetic sampling.

- Documented metal in the body, e.g. from fixed dental bridges, orthodontia braces, IUDs
containing metal or surgical screws.

- Weight and height dimensions that result in size exceeding the capability of the MRI
bore circumference is exclusionary.

- Chemotherapy.

- NIMH employees/staff and their immediate family members will be excluded from the
study per NIMH policy

Siblings who do not qualify for the 2-day or 1-day study, may participate in the limited
phenotyping arm in which only a psychiatric interview and a blood draw for genetic analysis
(SCID-DNA) will be performed, case control analysis or be included as part of a trio (one
parent, one sibling, one patient) to study genetic transmission from parents to
offsprings.. All parents are eligible for the study.

Healthy Controls Inclusion Criteria:

To be eligible for this research study, healthy volunteers must be:

- Between the ages of 18 and 55

- Fluency in English is required

Healthy Controls Exclusion Criteria:

They will not be eligible if:

- They have history of DSM IV-R psychiatric diagnosis or severe chronic medical illness
at the time of the study.

- They have a history of any (excepting nicotine-related) DSM5-defined moderate to
severe substance use disorder (or DSM-IV-defined substance dependence).

- They have a cumulative lifetime history of any (excepting nicotine-related)
DSM5-defined mild substance use disorder (or any DSM-IV-defined substance abuse),
either in excess of 5 years total or not in remission for at least 6 months.

- They may not be eligible for the 2-day or 1-day study if they have a first-degree
relative with history of schizophrenia spectrum disorders. However, they may be
included in the SCID_DNA or case control analyses..

- Documented presence of metal such as orthodontia braces, surgical screws or IUD of
metal composition.

- Healthy volunteers must be free of learning disabilities.

- NIMH employees/staff and their immediate family members will be excluded from the
study per NIMH policy