Frontostriatal Disorder of Cerebral Metabolism in Never-Medicated Schizophrenics

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).…”

Putamen Mitochondrial Energy Metabolism Is Highly Correlated to Emotional and Intellectual Impairment in Schizophrenics

“…The field has primarily benefited from such brain imaging techniques as PET and MRI and, from these, several cohesive themes have emerged. In this regard, the concept of "hypofrontality" has played a central role in our understanding of the disease (Siegel et al 1993;Buchsbaum et al 1992). However, assumptions about complex patterns of altered brain function are giving way to theories that attempt to define schizophrenia based upon alterations in a fundamental cognitive process (Sabri et al 1997;Andreasen et al 1997;Andreasen 1997).…”

Abnormalities in the Distributed Network of Sustained Attention Predict Neuroleptic Treatment Response in Schizophrenia

“…The new findings were consistent with earlier animal and human studies of basal ganglia involvement in attentional processes (see Mesulam, 1981 andCohen et al, 1992 for references). The importance of this finding for understanding the phenotypic expression of schizophrenia attained greater significance as a result of the findings of Buchsbaum and his colleagues (Buchsbaum et al 1992a). These investigators not only found diminished basal ganglia metabolism in addition to diminished frontal cortex metabolism in patients never medicated before with neuroleptics, but also that lower subcortical metabolic rates, prior to neuroleptic treatment, predicted a favorable clinical response to haloperidol (Buchsbaum et al 1992c) and clozapine (Buchsbaum et al 1992b).…”

“…Sustained attention on continuous performance tasks (CPT) has served as a laboratory model of this failure in positron emission tomography (PET) studies of regional glucose metabolic rates (Cohen et al 1988a). In PET studies (Buchsbaum et al 1990(Buchsbaum et al , 1992aCohen et al 1987), medication-withdrawn and neuroleptic-naive patients with schizophrenia performing CPT, and in our study, regardless of performance and medication status, were found to have abnormally low functional activity of the midprefrontal cortex area that served as the biological determinant of this task in normal controls (Cohen et al 1987(Cohen et al , 1988c(Cohen et al , 1992. These studies, although consistent with earlier data from a variety of methods on the importance of the right prefrontal cortex in attentional processes (Mesulam 1981), and subsequent and concurrent other PET studies utilizing cerebral blood flow as a measure of activation (Posner and Petersen 1990), were all performed at low resolutions and most, if not all, with calculated attenuation corrections.…”