Effect of a Haloperidol Challenge on Regional Brain Metabolism in Neuroleptic-Responsive and Nonresponsive Schizophrenic Patients

Abstract

The metabolic response to drug challenge separates treatment responders from nonresponders and normal subjects. The results suggest that subtyping of schizophrenia (and other psychiatric disorders) can be achieved by measuring the physiologic response to a pharmacologic challenge in vivo with chemical brain-imaging techniques.

Cells in midline thalamus, central amygdala, and nucleus accumbens responding specifically to antipsychotic drugs

“…There is evidence from post mortem and in vivo imaging studies of abnormalities of nucleus accumbens, thalamus, and amygdala in individuals with psychotic disorders (Stevens 1973;Tamminga et al 1992;Bogerts 1993;Andreasen et al 1994;Buchsbaum et al 1996;Nelson et al 1998;Lawrie et al 1999;McCarley et al 1999;Gur et al 2000;Byne et al 2001;Ende et al 2001). There is also preliminary evidence in human subjects that, as in laboratory animals, these regions may respond to antipsychotic drugs (Lewis et al 1992;Bartlett et al 1994Bartlett et al , 1998Yurgelun-Todd et al 2000;Cohen and Yurgelun-Todd 2001). Thus the findings presented here are consistent with a larger body of data suggesting that cells of the nucleus accumbens, midline thalamus and Fig.…”

Treatment-Resistant Schizophrenia Patients Show Elevated Anterior Cingulate Cortex Glutamate Compared to Treatment-Responsive

“…1,9 Additionally, administration of the D2 antagonist haloperidol produced significant metabolic reductions in treatment-resistant patients compared to responsive patients, suggesting that resistant patients might have reduced presynaptic dopamine reserve compared to responsive patients. 10 Further support for the idea that treatment resistance is nondopaminergic comes from studies using drugs to deplete presynaptic dopamine stores. [11][12][13] These studies have found no benefit from dopamine depletion in treatment-resistant patients, in contrast to the reduction in psychotic symptoms that is seen in most patients.…”

Association of serum VEGF levels with prefrontal cortex volume in schizophrenia

“…4 A number of findings from functional brain imaging studies have reported alterations in regional cellular energy metabolism and blood flow in patients with schizophrenia. 5,6 Furthermore, various cognitive deficits and symptom dimensions observed in patients with schizophrenia are often associated with specific patterns of regional blood flow. [7][8][9] It is known that impairments in cellular metabolic activity will change the demand for oxygen and glucose, which could stimulate the compensatory changes in blood flow via angiogenesis.…”