Neuroimaging of Dopamine Metabolism in Normal and Psychiatric Patients

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.