R. Rzanny

Brain activation during cognitive stimulation with the Wisconsin Card Sorting Test--a functional MRI study on healthy volunteers and schizophrenics.

It has been demonstrated by single photon emission computed tomography (SPECT) and positron emission tomography (PET) that frontal brain regions are stimulated during performance of the Wisconsin Card Sorting Test (WCST). The WCST is also regarded as one of the standard tests for the assessment of frontal activity in brain imaging studies of schizophrenia. In this study cerebral activation was assessed by means of functional magnetic resonance imaging (fMRI). In healthy volunteers WCST stimulation resulted in a right lateralized frontal activation. In 13 chronic schizophrenics on stable neuroleptic medication, a lack of activation in the right prefrontal cortex and--as a trend--an increased left temporal activity during execution of the WCST was noted compared to controls. Since a one-slice technique was used, no information about the activation pattern in adjacent brain regions was obtained. However, as fMRI possesses a superior spatial resolution compared to SPECT and PET, the anatomical localization of the activation effect in the measured slice can be defined more precisely. Beside these methodological considerations, the results are discussed in relation to prior findings of a reduced ability of schizophrenics to coordinate cerebral function.

Metabolic mapping using 2D 31P-MR spectroscopy reveals frontal and thalamic metabolic abnormalities in schizophrenia

(31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS) allows in vivo investigation of cerebral phospholipid and energy metabolism. Using 2D chemical shift imaging, this method can be applied to study multiple brain areas and to assess concentrations of both phospholipids and high-energy phosphates. The purpose of our study was to assess multiregional metabolic profiles in schizophrenia using a 2D-resolved MRS technique, and to assess the intercorrelation of findings. We applied (31)P-MRS chemical shift imaging in 31 schizophrenia patients (12 antipsychotic-naïve first-episode and 19 antipsychotic-free multi-episode patients) and 31 healthy age- and sex-matched controls. Spatially resolved maps were compared for the main metabolites of the (31)P spectrum. Metabolites of phospholipid (PME and PDE) and energy (PCr and Pi) metabolism were significantly reduced in bilateral prefrontal and medial temporal (including hippocampal) brain regions, caudate nucleus, thalamus and anterior cerebellum as compared to controls. Moreover, factor analysis of these changes showed a characteristic spatial pattern of changes, which demonstrates significant associations between alterations of phospholipid and energy metabolism, and between metabolic alterations and severity of symptoms (BPRS total score, but not SANS or SAPS scores). This suggests a pattern of intercorrelated changes of these metabolic markers. Results support the notion of disturbed phospholipid turnover in schizophrenia, probably unrelated to prior pharmacological treatment, and associated with increased energy demand.

31P magnetic resonance spectroscopy in the dorsolateral prefrontal cortex of schizophrenics with a volume selective technique—preliminary findings

Pettegrew et al (Arch Gen Psychiatry 48:563-568, 1991) were the first to determine abnormalities concerning phospholipids and high energy metabolites in the dorsolateral prefrontal cortex of drug-naive schizophrenics with 31P magnetic resonance spectroscopy (MRS). Other investigations could not replicate these findings. We included in our study 13 schizophrenic inpatients and 14 age-matched controls. Whereas Pettegrew et al found increased levels of phosphodiesters and decreased levels of phosphomonoesters we measured decreased levels of phosphodiesters in the schizophrenics as compared to controls. One possible explanation for the contradictory findings of the both trials might be the different localization techniques used.

Antipsychotic drug effects on left prefrontal phospholipid metabolism: A follow-up 31P-2D-CSI study of haloperidol and risperidone in acutely ill chronic schizophrenia patients

INTRODUCTION ³¹Phosphorous magnetic resonance spectroscopy (2D chemical shift imaging, CSI) allows multiregional study of membrane phospholipids and high-energy phosphates in vivo. Increased membrane lipid turnover and impaired energy supply have repeatedly been shown in first-episode schizophrenia patients, and might be a target of drug actions other than dopamine receptors. Here, we explored differential metabolic effects of a typical vs. an atypical antipsychotic on brain phospholipids. METHODS We applied 2D-CSI MR spectroscopy in 17 recurrent-episode schizophrenia patients off antipsychotics at baseline and at follow-up after 6 weeks, during which 7 patients were treated with haloperidol (10-16 mg/d) and 10 with risperidone (4-6 mg/d). Psychopathology changes were assessed using PANSS, BPRS and CGI scores. RESULTS Follow-up analysis using repeated measure ANOVA revealed different effects of both antipsychotic agents: while risperidone generally increased metabolite levels, haloperidol showed a tendency to decrease them. This diverging effect was significant for ATP levels in the left lateral frontal cortex. Furthermore, risperidone increased ATP in the left dorsolateral prefrontal cortex, left anterior temporal cortex and left insular cortex, basal ganglia, and anterior cerebellum, along with left frontal and prefrontal increase of PCr, PDE and PME in these brain regions. CONCLUSION Risperidone seems to stimulate neuronal and synaptic phospholipid remodeling in left frontal and prefrontal regions, and to a lesser extent also in temporal and insular cortices. We discuss these effects with respect to clinical effects on negative and cognitive symptoms, as well as interaction of phospholipid metabolism with glutamatergic neurotransmission.

Decreased frontal activation of schizophrenics during stimulation with the continuous performance test—A functional magnetic resonance imaging study

The Continuous Performance Test (CPT) has become an essential constituent of the neuropsychological investigation of schizophrenia. Also, a vast number of brain imaging studies, mostly PET investigations, have employed the CPT as a cognitive challenge and established a relative hypofrontality in schizophrenics compared to controls. The aim of the present investigation was to clarify whether this predescribed hypofrontality could also be verified using functional magnetic resonance imaging (fMRI). 20 healthy volunteers and 14 schizophrenics on stable neuroleptic medication were included. Imaging was performed using the CPT-double-T-version and a clinical 1.5 T MRI-scanner with a single slice technique and a T(2)*-weighted gradient-echo-sequence. The schizophrenics exhibited a decreased activation in the right mesial prefrontal cortex, the right cingulate and the left thalamus compared to controls. These results obtained by fMRI are discussed in relation to published findings using PET.

Neuropsychological and NMR-volumetric findinds in positive and negative schizophrenic patients

Schizophrenic patients treated with seroquel (n = 4; 700-750 mg/d) and haloperidol (n = 5; 10-20 mg/d) were investigated by means of IBZM-SPECT. Two striatal ROts and two frontal ROts were each pooled together and the average counts/pixel were calculated. The S / F ratio was calculated between average count-rates in the striatum and the frontal cortex. Under treatment with haloperidol a low S / F ratio (1.08 _+ 0.04) could be shown, which suggests a high occupancy of striatal D2 receptors (88_+ 6%). Under therapy with the new antipsychotic substance seroquel, the S / F ratios were high (1.59 ± 0.10), indicating only a minor striatal D2 blockade (17 ± 10%). These results are in line with the lower incidence of EPMS in patients treated with seroquel.