Tomo Hashiguchi

Proton magnetic resonance spectroscopy of the left medial temporal and frontal lobes in chronic schizophrenia: preliminary report

Proton magnetic resonance spectroscopy (MRS) was performed in 30 medicated schizophrenic patients and 30 normal subjects. Two groups, each containing 15 schizophrenic patients and 15 age-and sex-matched normal subjects, received MRS examinations for different volumes of interest, either the frontal lobe or the medial temporal lobe. Schizophrenic patients showed a decrease in the ratios of N-acetylaspartate (NAA)/choline-containing compounds (Cho) and NAA/creatine-phosphocreatine (Cr). The patients also showed an increase in the ratio of Cho/Cr in the left medial temporal lobe but not in the left frontal lobe. The age at onset of illness correlated positively with the ratios of NAA/Cho and NAA/Cr in the medial temporal lobe. No significant correlation was observed between the ratios of NAA/Cho, NAA/Cr, or Cho/Cr in the left medial temporal and frontal lobes and clinical symptomatology as assessed by the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scale.

Reduction in hippocampal formation volume is caused mainly by its shortening in chronic schizophrenia: Assessment by MRI

We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 18 men with chronic schizophrenia and in 18 age-matched healthy subjects to test in living patients the findings of a previous postmortem study. The schizophrenic patients showed bilaterally shortening (left, -6%; right, -9%) and volume reduction (left, -9%; right, -11%) of the hippocampal formation (HF). Volumes of HF correlated positively with HF length in the schizophrenic patients. The reduction in bilateral HF volumes was small after controlling for HF lengths (left, -3%; right, -3%). In schizophrenic patients, significant negative correlations were found bilaterally between the length of HFs and the scores for attention, bizarre behavior, and positive formal thought disorder. The results suggest that the volume reduction seen in the HFs of schizophrenic patients was caused mainly by a shortening of the HF and that these clinical symptoms may be associated with shorter HF length.

Metabolite changes with age measured by proton magnetic resonance spectroscopy in normal subjects.

Abstract  To determine whether there are metabolite changes in the left medial temporal and frontal lobes with aging, we performed proton magnetic resonance spectroscopy in 36 normal subjects. The N‐acetylaspartate/creatine‐phosphocreatine ratio in the medial temporal lobe tended to be decreased in subjects over 60 years of age. The ratio decrease in the frontal lobe related to aging was lower than that in the medial temporal lobe. There were no significant differences in the metabolite ratios between males and females. These findings suggest that structures in the medial temporal lobe may be more susceptible to neuronal dysfunction associated with aging than those in the frontal lobe.

Haloperidol Improves Membrane Phospholipid Abnormalities in Temporal Lobes of Schizophrenic Patients

Using 31P magnetic resonance spectroscopy, we examined changes in the levels of phosphorus metabolites in the temporal lobes of 13 schizophrenic patients before and 12 weeks after initiating haloperidol treatment. Spectra were obtained from a volume of interest positioned in each temporal lobe. Findings were compared with those in 13 age- and gender-matched healthy subjects. Prior to treatment the patients showed higher levels of phosphodiesters (PDE) in both temporal lobes than healthy subjects. Haloperidol administration significantly reduced the excess of PDE in the left temporal lobe, although the PDE concentration remained somewhat higher bilaterally than in controls. Treatment was associated with a decline in the total symptom score according to the Brief Psychiatric Rating Scale and the score for positive symptoms showed a relatively high correlation with reduction in PDE level in the left temporal lobe. These preliminary results suggest that haloperidol may partially normalize disturbed metabolism or abnormalities in components of membrane phospholipids in the left temporal lobe of untreated schizophrenic patients, paralleling symptom alleviation.

31P magnetic resonance spectroscopy of the medial temporal lobe of schizophrenic patients with neuroleptic-resistant marked positive symptoms

Abstract31P magnetic resonance spectroscopy was performed in 16 medicated schizophrenic patients with neuroleptic-resistant marked positive symptoms and in 16 healthy volunteers matched for age and sex in order to determine what changes in phosphorus metabolites are detected in such patients as compared to the controls. The schizophrenic patients showed an increased level of phosphodiesters in the bilateral medial temporal lobes. They also showed a decrease in the level of β-ATP in the left medial temporal lobe. These findings suggest that schizophrenic patients with prominent positive symptoms refractory to neuroleptics may have a disturbance of bilateral membrane phospholipid and left-sided high-energy phosphate metabolism in the medial temporal lobe.

Cavum septum pellucidum in schizophrenia: a magnetic resonance imaging study.

Abstract In order to determine if cavum septum pellucidum (CSP) is more prevalent in schizophrenic patients, we studied 72 Japanese patients who fulfilled the DSM‐III‐R criteria for schizophrenia and 41 normal controls. Sagittal, 1 mm thick magnetic resonance imaging slices of the entire cranium were obtained using a gradient‐echo pulse sequence, and coronal and axial images were reconstructed for assessment. A CSP was observed in 34 patients (47.2%) and in 16 controls (38.0%). Although the CSP appeared to be more prevalent in schizophrenic patients, this difference was not statistically significant. However, schizophrenic patients with a history of long‐term institutionalization had a higher incidence of CSP compared with patients who had not been admitted to hospital for more than 3 years (68.2 vs 38.0%). These results suggest that the CSP may be a pathophysiology that characterizes schizophrenic patients with poor prognoses.

Shortening of the hippocampal formation in first‐episode schizophrenic patients

Abstract Shortening of hippocampal formation (HF) in chronic schizophrenic patients have been demonstrated in our previous study. The purpose of the present study is to test if shortening of the HF occurs in schizophrenic patients suffering their initial psychotic episode. We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 20 first‐episode schizophrenic patients, 21 chronic schizophrenic patients, and 25 healthy subjects. Both groups of schizophrenic patients demonstrated significant shortening of the HF compared with normal controls (first‐episode schizophrenia, 5.3%; chronic schizophrenia, 8.0%). However, the HF length was not significantly different between the first‐episode and chronic schizophrenic patients. No significant correlation was seen between the HF length and the duration of illness in chronic schizophrenic patients. These results suggest that the HF shortening observed in schizophrenic patients may be genetic and/or developmental in origin.

Distribution of nifedipine- and ω-conotoxin GVIA-sensitive Ca2+ channels in cultured rat neocortical neurons

L- and N-type voltage-dependent calcium channels are widely distributed in neurons of the CNS. To investigate their subcellular distributions on CNS neurons, intracellular calcium concentration ([Ca2+]i) increase in response to high potassium ([K+]) solution was detected in primary cultured rat neocortical neurons using the calcium indicator dye Oregon Green with a confocal laser scanning microscope. Extracellular application of 90 mM [K+] solution induced fluorescence increase in a manner dependent on extracellular [Ca2+]. The increase was partially blocked by 10 microM nifedipine, and the reduction was higher in cell bodies compared to dendritic processes. In contrast, omega-conotoxin GVIA reduced the 90 mM [K+] induced fluorescence increase more in the dendritic processes. The results demonstrated the heterogeneous distribution of nifedipine- and omega-conotoxin GVIA-sensitive calcium channels, which may suggest a functional difference in nifedipine- and omega-conotoxin GVIA-sensitive channels in cultured neocortical neurons.

122 Different distribution of L- and N-type Ca2+ channel in rat neocortical neurons

Naoshi FUJIWARA, Ren-Zhi ZHAN, Koki Shimoji To elucidate the mechanism of pHi changes induced by membrane depolarization, changes in pHi and [Ca2+]i induced by high K+, veratridine, NMDA were investigated in rat hippocampal slices using BCECF or fura-2. All these agents elicited a decrease in pHi and an elevation of [Ca2+]i in the CA1 pyramidal cell layer. Although the [Ca2+]i increase was completely suppressed in Ca 2+ free media, a major part of each pHi acid shift remained unchanged. Glucose-deprivation reduced pHi acid shifts induced by high K+ or NMDA by twothird. Anthermore, lactate contents significantly increased in slices exposed to the depolarizing agents. The results suggest that pHi acid shifts produced by the depolarizing agents are mainly due to lactate accumulation. A Ca2+-dependent process may partially cause pHi acid shifts. Since an increase in [H+] enables to attenuate neuronal activity, glycolytic acid production promoted by depolarization may contribute to prevent excessive neuronal excitation.

Metabolite changes with age measured by proton magnetic resonance spectroscopy in normal subjects

To determine whether there are metabolite changes in the left medial temporal and frontal lobes with aging, we performed proton magnetic resonance spectroscopy in 36 normal subjects. The N-acetylaspartate/creatine-phosphocreatine ratio in the medial temporal lobe tended to be decreased in subjects over 60 years of age. The ratio decrease in the frontal lobe related to aging was lower than that in the medial temporal lobe. There were no significant differences in the metabolite ratios between males and females. These findings suggest that structures in the medial temporal lobe may be more susceptible to neuronal dysfunction associated with aging than those in the frontal lobe.