Tsuyoshi Fukuzako

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.

Proton magnetic resonance spectroscopy of basal ganglia in chronic schizophrenia

Proton spectra in the regions of the right and left basal ganglia were studied in 14 medicated patients with chronic schizophrenia using proton magnetic resonance spectroscopy (1H MRS). Ratios of N-acetyl-aspartate (NAA) to choline-containing compounds (Cho) were significantly reduced in the bilateral basal ganglia regions compared to normal subjects. The relative level of Cho was increased in the left basal ganglia region in comparison to normal subjects. This finding suggests the presence of disturbances in phospholipid metabolism in the basal ganglia. The level of NAA was decreased in the bilateral basal ganglia regions, which may indicate neuronal dysfunction. The 1H MRS study demonstrated dysfunctions in the basal ganglia regions in medicated patients with chronic schizophrenia.

Phosphorus magnetic resonance spectroscopy in schizophrenia: Correlation between membrane phospholipid metabolism in the temporal lobe and positive symptoms

1. To determine any correlations between phosphorus metabolites in the temporal lobes and clinical symptoms in schizophrenic patients, the authors performed 31phosphorus magnetic resonance spectroscopy in 31 medicated patients and age- and sex- matched normal subjects. 2. Schizophrenic patients demonstrated an increased level of phosphodiesters (PDE) in the temporal lobes bilaterally and a decreased level of beta-adenosine triphosphate (beta-ATP) in the left temporal lobe. 3. A significant positive correlation was observed between the level of PDE in the left temporal lobe and the score of positive symptoms on the Brief Psychiatric Rating Scale. 4. These results suggest that altered membrane phospholipid metabolism in the left temporal lobe is associated with neuroleptic-resistant positive symptoms in schizophrenic patients.

Hippocampal volume asymmetry and age at illness onset in males with schizophrenia.

To determine whether there are disturbances of hippocampal volume asymmetry in schizophrenic patients, we obtained contiguous, I-mm-thick magnetic resonance images in 28 males with chronic schizophrenia and in 28 age-matched healthy males. The schizophrenic patients showed a bilateral reduction in volume of the hippocampal formation (HF; left 7.0%; right 8.7%). This reduction was significantly associated with the severity of disorganization syndrome (P < 0.0005). A significant asymmetry in the HF volume was found in the control subjects (P = 0.006), but not in the patients (P = 0.40). There was a significant positive correlation between the asymmetry index and the patient’s age at the onset of schizophrenia (r = 0.46,P = 0.01). Results indicate that a disturbance in the normal asymmetry of the HF may be a characteristic in schizophrenia, particularly in patients with an early onset of the illness.

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.

Subtype-associated metabolite differences in the temporal lobe in schizophrenia detected by proton magnetic resonance spectroscopy

Brain imaging studies have indicated that the medial temporal lobe functions aberrantly in schizophrenic patients. Both diagnostic subtype and gender may affect functional and morphologic abnormalities in this region. We investigated subtype- and gender-associated differences in metabolites in the left medial temporal lobe in 40 medicated schizophrenic patients by proton magnetic resonance spectroscopy and compared findings with those in 40 healthy control subjects. Peaks corresponding to N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine-phosphocreatine (Cr), and inositol were measured. Schizophrenic patients showed a decrease in the NAA/Cr ratio in the left medial temporal lobe, and patients with the disorganized subtype of illness showed significantly lower NAA/Cr and Cho/Cr ratios than those with paranoid schizophrenia. The NAA/Cr ratio in patients with the undifferentiated subtype also was significantly lower than in the paranoid subtype. No significant associations were observed between metabolite ratios and clinical symptom scores, age at onset of illness, or gender. These findings suggest that patients with the disorganized and undifferentiated subtypes have greater impairments in neuronal integrity or function in the left medial temporal lobe than patients with other subtypes of schizophrenia.

Correlation of third ventricular enlargement and EEG slow wave activity in schizophrenic patients

Twenty-eight schizophrenic patients and 22 normal control subjects underwent magnetic resonance imaging (MRI) and topographic electroencephalography (EEG) in a study attempting to correlate morphological and electrophysiological findings. Schizophrenic patients had larger anterior horns of the lateral ventricles and third ventricles than normal control subjects. Schizophrenic patients showed more delta wave activity in the right parietooccipital region than normal control subjects. Alpha 2 wave activity was reduced in the entire region in schizophrenic patients. In schizophrenic patients, a significant positive correlation was seen between the area of the third ventricle and delta wave activity in the right occipital region. These results suggest that schizophrenic patients may have a dysfunction of diencephalic structures associated with morphological abnormality.

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.