Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

“…Particularly, ego-disorders (Rüm-mele and Gnirss 1961;Vollenweider et al 1997), affective changes (Rümmele and Gnirss 1961), loosened associations (Spitzer et al 1996) and perceptual alterations commonly seen in psilocybin-induced psychosis are also observed in incipient acute schizophrenic stages (Bowers and Freedman 1966;Heimann, 1986;Gouzoulis et al 1994). In support of these suggested clinical similarities, we recently found that psilocybin produced a marked prefrontal and anterior cingulate activation in normal subjects comparable to the hyperfrontal pattern observed in some (Cleghorn et al 1989;Ebmeier et al 1993Ebmeier et al , 1995Catafau et al 1994 1994;Ebmeier et al 1995;Sabri et al 1997) but not all (Andreasen et al 1992;Buchsbaum et al 1992;Liddle et al 1992;Siegel et al 1993) acute schizophrenic patients. A number of functional animal studies have suggested that indoleamine (psilocybin, LSD) and phenylethylamine (DOI, mescaline) hallucinogens produce their psychotomimetic effects primarily through excessive stimulation of 5-HT, and 5-HT 2A receptors in particular (McKenna et al 1989;Pierce and Peroutka 1989;Aghajanian 1994;Sipes and Geyer 1994;Padich et al 1996).…”

Clinical and Sensorimotor Gating Effects of Ketamine in Normals

“…However, this is not a consistent finding. In fact, studies in unmedicated acutely relapsed schizophrenics with robust positive symptoms have reported a hyperfrontal metabolic pattern (Volkow et al 1986;Wiesel et al 1987;Cleghorn et al 1989;Ebmeier et al 1993;Parellada et al 1994). The extent to which ketamine administration is an accurate model of brain metabolic changes in schizophrenia needs further clarification.…”

Mitochondrial Function is Differentially Altered in the Basal Ganglia of Chronic Schizophrenics

“…While the power of PET as a tool for understanding 'statedependent' brain function and receptor characteristics, as well as offering excellent patient control, is generally undisputed, the sheer bulk of data created by researchers in the field has generated a disconcertingly diffuse base of evidence for which regions may be involved in the disease. Although a general trend implicating reduced metabolism in cortical and sub-cortical regions has formed the foundation for assumptions about a possible defect in schizophrenics (Buchsbaum et al 1982(Buchsbaum et al , 1992Tamminga et al 1992;Siegel et al 1993), opposite findings have been made (Early et al 1987;Wiesel et al 1987;Cleghorn et al 1989).As a complement to imaging studies, our laboratory has applied a strategy involving the post-mortem measurement of the mitochondrial respiratory chain en- COX Activity and Schizophrenia 373 zyme cytochrome-c oxidase (COX) in an attempt to localize altered brain function in schizophrenia. This approach is based upon a strong body of evidence which indicates that neuronal COX is highly regulated by the energy demands of the cell and as such represents an endogenous marker of cellular energy metabolism over time (Wong-Riley 1989).…”