Brain cells communicate with each other by releasing chemicals called neurotransmitters. In
order for brain cells to transfer information, one cell will release a neurotransmitter that
will be recognized by a receptor located on surface of another cell. One such
neurotransmitter is dopamine.
Abnormal dopamine transmission has been seen in patients with substance abuse and different
neuropsychiatric disorders including schizophrenia.
A radioactive drug called IZBM (I-123 iodobenzamide) can also bind to certain dopamine
receptors. IZBM can be seen by Single Photon Emission Tomography (SPECT). Therefore, by
using IZBM and SPECT scans, researchers can find and "map" the location of dopamine
receptors in the brain.
Patients participating in this study must also have been selected for other genetic studies
being conducted at the NIMH. Patients with schizophrenia will be selected from a NIMH
research study titled, "Neurobiological Investigation of Patients with Schizophrenia
Spectrum Disorders and Their Siblings" (95-M-0150). Normal patient volunteers will be
selected from another NIMH study titled, "Inpatient Evaluation of Neuropsychiatric Patients"
(89-M-0160). All aspects of clinical care and genetic analysis of these patients will be
covered in these studies, while information pertaining to IBZM SPECT scans will be covered
in this study.
This study will not directly benefit patients participating in it. However, information
gathered may contribute to faster and more accurate diagnosis of schizophrenia and
eventually better treatment for the disorder.
Abnormalities in dopaminergic neurotransmission have been described in substance abuse and
different neuropsychiatric disorders including schizophrenia. [I-123] IBZM is a radioligand
that has been widely employed for SPECT imaging of dopamine type 2 and type 3 receptors (D2
and D3, respectively) and fluctuations in levels of endogenous dopamine. [I-123] IBZM SPECT
has been used in the SPECT Lab of the Clinical Brain Disorders Branch for several years
without adverse effects. Pharmacological effects of IBZM are unlikely due to the minimal
amounts used and have not been observed. We propose to use [I-123] IBZM SPECT to explore
following questions: 1) Can a previously found relationship between N-acetylaspartate (NAA)
measures in the dorsolateral prefrontal cortex and striatal dopamine activity in patients
with schizophrenia be replicated and is it also found in normal subjects? 2) Do allelic
variants of genes for the dopamine type 2 (DRD2) and type 3 (DRD3) receptors, the dopamine
transporter (SLC6A3), or enzymes involved in dopamine biosynthesis (TH) and metabolism
(COMT, MAOA) affect D2 receptor availability in vivo?
This technical protocol describes the procedural aspects of [I-123]IBZM SPECT. It is not
intended to be sufficient on its own for a clinical study. All subjects volunteering for
this study will be recruited from among individuals who have previously consented to
participate in clinical studies under one of two NIH protocols that include genetic testing.
Schizophrenia patients will be recruited from among NIMH inpatients participating under
NIH protocol #89-M-0160, "Inpatient Evaluation of Neuropsychiatric Patients" (Egan 1999a).
Normal volunteers will be recruited from among those participating under NIH protocol
#95-M-0150, "A Neurobiological Investigation of Patients with Schizophrenia Spectrum
Disorders and Their Siblings" (Egan 1999b), which includes recruitment of a normal control
group whose first degree relatives are free of mental illness. All details related to
clinical care and genetic analysis are contained in those two protocols and their associated
consent forms; all details related to [I-123]IBZM SPECT studies, per se, are discussed in
this protocol, which requires a separate informed consent from each volunteer.
Patients with schizophrenia will be recruited exclusively from among inpatients who are
participating in clinical studies of the Clinical Brain Disorders Branch of NIMH under NIH
protocol #89-M-0160 (Egan 1999a) and for whom genetic data is already available.
Normal volunteers will be recruited exclusively from among individuals who have
volunteered for studies under NIH protocol #95-M-0150 (Egan 1999b) as normal control
subjects and for whom genetic data is already being analyzed.
Pregnancy: All women of childbearing age must undergo a pregnancy test prior to injection
or radioactive isotope. If the pregnancy test is positive or if the woman has reason to
believe she might be pregnant, she will be excluded from this study.
Breastfeeding: Women who are breastfeeding will be excluded from this study to avoid
unwarranted risk to their children.
Iodine sensitivity: Subjects with a prior reaction to iodine, iodine compounds, or
shellfish will be excluded from this study. Also, subjects with a history of thyroid
disease or dysfunction will be excluded from this study.
Substance abuse: Subjects with a history of recent substance abuse will be excluded from
Metal objects in body: Subjects with metal objects in their bodies as specified in our MRI
protocol (91-M-0124) will be excluded from this study.
INCLUSION CRITERIA FOR PATIENTS WITH SCHIZOPHRENIA:
Prior participation as a NIMH inpatient under NIH protocol #89-M-0160.
Schizophrenia diagnosis according to DSM-IV criteria.
EXCLUSION CRITERIA FOR PATIENTS WITH SCHIZOPHRENIA:
Coexistence of another mental illness at the time of the study. If the patient has
experienced other mental illnesses in the past (e.g. a learning disability or major
depression), then this should be judged to be fully recovered.
INCLUSION CRITERIA FOR NORMAL CONTROLS:
Prior participation as a normal volunteer under NIH protocol #95-M-0150.
No Axis I or Axis II diagnoses.
EXCLUSION CRITERIA FOR NORMAL CONTROLS:
Subjects with an Axis I or II disorder will be excluded.
Subjects with concomitant medical or neurological disorders which require ongoing
medication, or which may affect the central nervous system will be excluded.