In SPDs, plasma homovanillic acid (HVA)
was found to be those higher in patients with SPD compared with normal controls83 and the plasma HVA concentrations were correlated with degree of psychotic-like symptomatology.83 In this study, group differences were abolished after covarying for psychotic-like symptoms. An identical configuration of results was found in another #all targets keyword# partially overlapping cohort of patients using cerebrospinal fluid (CSF) HVA.83 Another potential index of subcortical dopaminergic responsivity can be assessed by measuring plasma HVA responses to the glycopyruvic stressor, 2-deoxyglucose (2-DG). By blocking glucose absorption into brain cells of frontal lobe, 2-DG induces stress responses including plasma Cortisol and HVA increases following 2-DG administration. Patients with schizophrenia demonstrate elevated HVA responses to 2-DG compared to controls; schizotypal patients have normal responses and, compared with normal controls, Inhibitors,research,lifescience,medical reduced Cortisol responses. Functional and structural imaging studies of striatum point
to the possibility of increased dopaminergic activity. Thus, patients with Inhibitors,research,lifescience,medical SPD show increased striatal volume, particularly in ventral putamen, which may reflect dendritic proliferation secondary to increased dopaminergic activity. Increased metabolic Inhibitors,research,lifescience,medical activation
of ventral putamen in SPD compared with schizophrenia is also consistent with reduced dopaminergic inhibitory tone and may also be a promising imaging endophenotype for candidate gene studies. Finally, amphetamine, by releasing dopamine, will displace radiotracers that bind the D2 receptor, which can be evaluated using IBZM ([123I]iodobenzamide) as a radioligand in single-photon emission computed tomography (SPECT) studies or in PET studies using raclopride as Inhibitors,research,lifescience,medical a radioligand. A SPECT study utilizing IBZM as a ligand indicated that SPD subjects have displacement of IBZM following AV-951 amphetamine, which is intermediate between the markedly increased displacement values found in acute schizophrenic patients and normal controls. Raclopride displacement studies using PET scanning following amphetamine also suggest significant increases in raclopride displacement in schizophrenic patients88 and such studies are underway in SPD patients. These studies suggest that dopaminergic activity in subcortex is normal to modestly increased, but consistently less than that observed in acutely schizophrenic patients. Thus, the dopamine system may be better buffered in schizotypal patients, and dopaminergic indices may provide promising endophenotypes for a dimension of psychosis in schizophrenia.