PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations

The investigators will focus on mGluR5 PET binding as a surrogate measure for level of
activity of the mTOR kinase pathway. This study is being conducted by the New York State
Psychiatric Institute (NYPSI) and the Research Foundation for Mental Hygiene Inc (RFMH) and
will take place at Columbia University Medcial Center (CUMC) in New York City and at a
research office in Strasburg, PA. Subjects (n=20) with the CNTNAP2 mutation with
schizophrenia or a related condition will be recruited from the Amish and Mennonite
communities and brought to CUMC for detailed investigation. Affected individuals will be
compared to Old-Order Amish control patients drawn from the same families but not harboring
CNTNAP2 mutations (n=20). The primary measure will consist of mGluR5 PET binding in DLPFC.
In addition, secondary analyses will assess binding in other brain regions such as
hippocampus and visual cortex. Exploratory measures, as well as relationships between PET
mGluR5 binding and clinical symptomatology,will be assessed.

Inclusion Criteria:

Patients:

- Meets DSM-5 diagnostic criteria for psychotic disorder, including schizophrenia,
schizoaffective disorder or psychotic disorder not elsewhere classified

- Aged 18-59 years

- Genetic confirmation that patient carries CNTNAP2 mutation

- All patients will be of Amish and/or Mennonite descent

- Has a relative willing to be part of the study and this relative will travel with the
participant to Columbia University Medical Center in New York City and back to
Lancaster, PA

- In the judgment of the participant's treating physician as well as the evaluating
consenter, the patient is stable enough to travel and participate in the study

Control subjects:

- Aged 18-59 years

- Genetic confirmation that subject does not carry CNTNAP2 mutation

- First-degree or second-degree relative of subject of Amish/Mennonite descent with
CNTNAP2 mutation

Exclusion Criteria (for patients and controls):

- Positive urine toxicology for drugs of abuse, including cannabinoids, amphetamine,
benzodiazepines, barbiturates, cocaine, methadone, opiates, and phencyclidine

- Positive history of severe neurological illness or history of brain trauma

- Positive history of severe medical illness that would increase risk due to PET scan
procedure, or interfere with interpretation of research findings

- Low hemoglobin (Hb < 11 g/dL in males, Hb <10 g/dL in females)

- Lifetime exposure to radiation in the workplace, or lifetime history of participation
in nuclear medicine procedures, including research protocols. However, in case of
previous exposure to radioactivity due to research studies, subjects will be eligible
if all conditions listed below are fulfilled:

- research studies in question have been performed in the context of a protocol
from the Division of Translational Imaging (Anissa Abi-Dargham, M.D., Director)
or as part of a research study within another division at Columbia
University/NYSPI and the injected dose and dosimetry of the radiotracer are
known

- Except for research studies, the patient has had no lifetime exposure to
radiation in the workplace or in nuclear medicine procedures

- Adding the previous exposure to the exposure due to this study will result in a
yearly cumulative exposure lower than the limit defined by the FDA for research
subjects

- Blood donation within 8 weeks of study

- Presence of clinically significant brain abnormalities

- For female patients of child-bearing age who are not surgically sterilized and
between menarche and 1 year postmenopausal: Must test negative for pregnancy at the
time of enrollment and prior to PET scan based on a serum pregnancy test. Women who
are breast-feeding are also excluded.

- Metal implants, pacemaker, other metal (e.g., shrapnel or surgical prostheses) or
paramagnetic objects contained within the body which may present a risk to the
subject or interfere with the MR scan, as determined in consultation with a
neuroradiologist and according to the guidelines set forth in the following reference
book commonly used by neuroradiologist: "Guide to MR procedures and metallic
objects", F.G. Shellock, Lippincott Williams and Wilkins NY 2001.

- Medicinal patch, unless removed prior to the MR scan.

- Patients: Current treatment with clozapine and/or medications other than
antipsychotics/PRN anxiolytics

- Use of the medications that would interfere with mGluR5 binding, including
lamotrigine, gabapentin, topiramate, phenobarbital, pregabalin, zonisamide,
N-acetylcysteine, D-cycloserine

- Control subjects: Lifetime history of antipsychotic or antidepressant use