Left globus pallidus abnormality in never-medicated patients with schizophrenia.

Abstract

Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. We have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5 patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this frnding. No other abnormalities were found.Studies of cerebral blood flow (1-9) and metabolism (10-17, 41) have attempted to identify regional abnormalities in patients with schizophrenia. Unfortunately, at least two methodological problems have contributed to inconsistent findings. One important problem is the localization of specific anatomical regions within images of blood flow and metabolism. This problem is attributable to the lack of precise anatomical landmarks within these physiological images. One strategy for anatomical localization identifies regions based on visual inspection of the image; however, this strategy is imprecise, unreliable, and subject to observer bias. Another strategy identifies regions based on comparisons between tomographic images of blood flow and metabolism and an atlas of the brain, such that all planes are parallel to a standard reference plane (e.g., a horizontal plane through the canthomeatal line); however, this strategy may be inaccurate because of the variability in the relationship of the brain to standard craniofacial landmarks. A third strategy compares tomographic images of blood flow and metabolism to a computerized tomography or magnetic resonance image obtained in the same plane; however, this strategy cannot distinguish adjacent regions of gray matter and is uncertain in its ability to provide reliable comparisons among different subjects. (See ref. 18 for a review of these issues.)Another important problem is the physiological effect of antipsychotic medications on measurements of blood flow and metabolism. All but three previous studies (10,17,41) used patients with a history of antipsychotic drug use and withdrawal periods of less than a few weeks. Since the effects of antipsychotic drugs can last for many weeks [e.g., the inhibition of apomorphine-induced stereotopy (19)] or longer [e.g., tardive dyskinesia (20)], these studies cannot account for the possibility of persistent medication effects.We have now used positron emission tomography and a validated method of anatomical localization (18) to identify ...

The Brain Metabolic Patterns of Clozapine- and Fluphenazine-Treated Female Patients with Schizophrenia Evidence of a Sex Effect

“…That we observed changes that were larger on the right than on the left side of the basal ganglia in males (Cohen et al 1997) is consistent with a previous all-male PET study of neuroleptics (Buchsbaum et al 1992b). In contrast to the right-sided basal ganglia asymmetry in neuroleptictreated patients, our own study (Cohen et al 1998) and two other studies of either all-male or predominantly all-male patients (Buchsbaum et al 1987;Early et al 1987), not receiving neuroleptic medication, have suggested a left greater than right asymmetry in metabolic rates in the putamen. The basis of the underlying asymmetries in blood flow and metabolic rates in the basal ganglia of males may rest with asymmetries in the dopamine system.…”

“…In women, but not in men, clozapine is equally as effective in increasing basal ganglia metabolism as fluphenazine, and both clozapine and fluphenazine decrease cingulate metabolism. Because it is unlikely that the schizophrenic patients we have studied while performing CPT have abnormally low basal ganglia or abnormally elevated cingulate metabolism before treatment (see discussion in Cohen et al 1997 andCohen et al 1998;Kotrla and Weinberger 1995;Tamminga et al 1992;Early et al 1987), these sex differences would seem to strengthen the compensation hypothesis.…”

Increased resting perfusion of the hippocampus in high positive schizotypy: A pseudocontinuous arterial spin labeling study

“…To our knowledge, this is the first application of the ASL method to investigate differences in resting perfusion in a schizotypy group. Given that the study groups only differed on the presence of schizotypal traits, and that hippocampal hyperperfusion has been reported in patients with psychosis (Friston et al, 1992; Liddle et al, 1992; Malaspina et al, 2004; Pinkham et al, 2011; Schobel et al, 2013, 2009; Talati et al, 2014, 2015; although see Andreasen et al, 1997; Catafau et al, 1994; Early et al, 1987; Parellada et al, 1994), and in people at CHR of sychosis (Allen et al, 2017, 2016; Schobel et al, 2013), our study findings suggest that increased hippocampal activity (reflected in an elevation of regional perfusion) is also involved in the expression of subclinical psychotic‐like experiences.…”

“…Beyond the hippocampus, other brain regions of significantly elevated resting perfusion in schizophrenia patients compared with healthy controls have involved the basal ganglia and middle temporal lobes (Pinkham et al, 2011), cerebellum, brainstem, and thalamus (Scheef et al, 2010). Noteworthy, while not directly focusing on the hippocampus as a specific region, initial PET and SPECT studies did not find increased perfusion in medial temporal regions (Andreasen et al, 1997; Catafau et al, 1994; Early, Reiman, Raichle, & Spitznagel, 1987; Parellada et al, 1994). A possible source for the inconsistencies noted among individual studies is that resting perfusion research in patients with schizophrenia is complicated by antipsychotic exposure (Lahti et al, 2006; Lahti, Weiler, Holcomb, Tamminga, & Cropsey, 2009; Medoff, Holcomb, Lahti, & Tamminga, 2001).…”

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

“…The prefrontal cortex was examined based on our earlier findings (Cohen et al 1987) that the metabolic rates of prefrontal cortex regions of interest, but not regions of interest in the pre-motor or orbital frontal cortex were reduced in the schizophrenic patients. When the prefrontal cortex is referred to in the text in the comparison between groups, it is the mean of the left and right anterior and posterior ROIs of the frontal cortex in Planes B, C, and D. The basal ganglia was also examined for differences because of the reports of both abnormally high and abnormally low metabolic rates in schizophrenia (Buchsbaum et al 1992a;Early et al 1987;Resnick et al 1988;Wolkin et al 1985). When the multivariate analyses were significant, student t -tests were performed to localize the findings.…”