Toshiki Shioiri

Alterations in brain phosphorous metabolism in bipolar disorder detected by in vivo 31P and 7Li magnetic resonance spectroscopy.

Phosphorus-31 magnetic resonance spectroscopy (MRS), able to detect membrane metabolism and intracellular pH as well as energy metabolism in vivo, was applied to 17 bipolar patients in the manic state and the euthymic state. In nine of these patients, brain lithium concentration was simultaneously determined by means of lithium-7 MRS in order to clarify the effect of treatment with lithium on brain phosphorous metabolism. Both phosphomonoester (PME) peak area and intracellular pH were found to be higher in the manic state than in the euthymic state. These values in the euthymic state were lower than those in normal controls whose ages and sexes were matched with the patients. However, PME and intracellular pH did not correlate to brain lithium concentration. These findings coincide with a hypothesis that patients with bipolar disorder may have membrane abnormality in their euthymic state and state-dependent alteration of catecholaminergic activity may be a secondary phenomenon.

Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy

Brain phosphorus metabolism was measured by 31P-MRS in 15 patients with bipolar II disorder (BP II) and 14 patients with bipolar I disorder (BP I). Phosphocreatine (PCr)levels were significantly lower in patients with BP II in all three psychiatric states compared to 59 normal controls (PCr (%) was 13.5 +/- 1.5 (mean +/- SD) for controls, and 12.2 +/- 1.7, 12.1 +/- 1.3, 12.0 +/- 1.9 for hypomanic, euthymic and depressed bipolar II patients respectively). High values of phosphomonoester (PME) were found in BP II patients in the hypomanic and depressive states, but PME values in the euthymic state did not differ significantly from controls. Intracellular pH of BP II patients in all three psychiatric phases was similar to control values, whereas euthymic BP I patients had lower pH values. These results suggest that brain high energy phosphate metabolism may be impaired in BP II and that there may be pathophysiological differences between BP I and BP II.

Brain phosphorous metabolism in depressive disorders detected by phosphorus-31 magnetic resonance spectroscopy

Brain phosphorus metabolism was measured in 22 patients with depressive disorders. Ten of them had DSM-III-R bipolar disorder, and 12 had major depression. In bipolar patients, phosphomonoester (PME) and intracellular pH were significantly increased in the depressive state than in the euthymic state, while those values in the euthymic state were significantly low as compared to age-matched normal controls. Phosphocreatine (PCr) was significantly decreased in severely depressed patients compared to mild depressives. These findings suggest that high energy phosphate metabolism, intracellular pH and membrane phospholipid metabolism are altered in depressive disorders.

Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded 31P-MRS

High energy phosphate metabolites were measured using phase-encoded in vivo phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in both the left and right frontal lobes of 25 patients with bipolar disorder. Eleven patients were examined in the depressive state, 12 in the manic state, and 21 in the euthymic state. Twenty-one age-matched normal volunteers were also examined. The phosphocreatine (PCr) peak area percentage in the left frontal lobe in the patients in the depressive state was decreased compared with that in the normal controls. It was significantly negatively correlated with the Hamilton Rating Scale for Depression score evaluated at the time of 31P-MRS examination. The PCr peak area percentage in the right frontal lobe in the patients in the manic and the euthymic states was decreased compared with that in the controls. These results are compatible with previous reports describing reduction of glucose metabolism in the left frontal lobe in depressive patients with bipolar disorder and trait-dependent right hemisphere dysfunction in bipolar disorder.

Phosphorus-31 magnetic resonance spectroscopy and ventricular enlargement in bipolar disorder

Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) was used to examine whether reduced levels of phosphomonoesters (PME) were correlated with ventricular enlargement in 40 patients with bipolar disorder and 60 age-matched normal control subjects. Ventricular enlargement was assessed by magnetic resonance imaging (1H-MRI) using the following three methods: Evans ratio (ER), Huckman number (HN), and minimum distance of caudate nuclei (MDCN). Although MDCN and ER were significantly larger in the patient group, no significant correlations were found between 31P-MRS and 1H-MRI. PME was negatively correlated with age in bipolar disorder. Decreased levels of PME were found only in bipolar I disorder. Intracellular pH was positively correlated with duration of lithium treatment. These results suggest that the observed PME reduction was not related to ventricular enlargement, but the issue should be further studied with volumetric MRI analysis.

Decreased brain intracellular pH measured by 31P-MRS in bipolar disorder: a confirmation in drug-free patients and correlation with white matter hyperintensity.

Abstract The authors have previously reported decreased intracellular pH (pHi) in the frontal lobes in euthymic bipolar patients treated with lithium using 31P-MRS. White matter hyperintensity (WMHI) is frequently seen in bipolar disorder. To examine a possible effect of lithium on pHi and the relationship between pHi and WMHI, seven drug-free euthymic bipolar patients were examined, and T2-weighted MRI were examined in 14 previously reported bipolar patients. Drug-free patients showed significantly lower pHi than controls. WMHI was associated with low pHi and increased phosphodiester peak. These results suggest that decrease of pHi is not an effect of lithium but is instead related to the pathophysiology of illness. Decrease of pHi and increase of the PDE peak may be the biochemical basis of WMHI in bipolar disorder.

Quantitative proton magnetic resonance spectroscopy of the bilateral frontal lobes in patients with bipolar disorder.

BACKGROUNDnUsing 31P and 1H magnetic resonance spectroscopy (MRS) we previously reported that phosphocreatine was decreased in the left frontal lobe and choline-containing compounds were increased in the basal ganglia in the depressive state in patients with bipolar disorder. We applied quantitative 1H-MRS for further characterization of biochemical alteration in the frontal lobes of bipolar patients.nnnMETHODSnTwenty-three bipolar patients and 20 normal controls were examined by 1H-MRS with a 1.5T MR system. All patients were examined in the euthymic state, and eight patients were also examined in the depressive state. Volumes of interest of 2.5 x 2.5 x 2.5 cm were selected in the left and right frontal lobes. Absolute concentrations of N-acetyl-1-aspartate, creatine plus phosphocreatine, and choline-containing compounds were calculated from each metabolite peak.nnnRESULTSnCreatine concentration in the left frontal lobe in bipolar patients in the depressive state was significantly lower than that in the euthymic state. Creatine concentration in the right frontal lobe in the male patients was significantly higher than that in the female patients and a similar trend was also found in the control subjects.nnnCONCLUSIONSnWe found a state-dependent change of creatine metabolism in the left frontal lobe of bipolar patients. The present results are compatible with our previous report of decreased phosphocreatine measured by 31P-MRS in the left frontal lobe in bipolar disorder. We also found an effect of gender on the creatine concentration. There may be a gender difference in creatine transport function into the brain.

Correlations of phosphomonoesters measured by phosphorus-31 magnetic resonance spectroscopy in the frontal lobes and negative symptoms in schizophrenia

Frontal lobe dysfunction has been linked to negative symptoms of schizophrenia. We used phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to examine phosphorous metabolism in frontal brain regions in 26 schizophrenic patients compared with 26 sex- and age-matched control subjects. The relative signal intensities of phosphorous metabolites in frontal regions did not differ significantly between schizophrenic patients and control subjects. However, phosphomonoester levels were significantly decreased in frontal regions of 12 schizophrenic patients who had high scores on negative symptom subscales from the Brief Psychiatric Rating Scale (i.e., emotional withdrawal, motor retardation, and blunted affect) compared with 14 patients with low negative symptom scores on the same subscales and control subjects. The correlations between negative symptoms and phosphorous metabolism in the frontal lobes support the hypofrontality hypothesis in schizophrenia.

Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia

Magnetic resonance spectroscopy (one-dimensional chemical shift imaging) was used to measure membrane phospholipid metabolism and high-energy phosphate metabolism in the left and right frontal lobes of 27 schizophrenic patients. In the schizophrenic patients, the phosphomonoester peak area was decreased in bilateral frontal lobes compared with that in age-matched normal subjects. On the other hand, the peak area of beta-adenosine triphosphate was increased in the left frontal lobe in the schizophrenic group. The phosphocreatine peak area was increased in the left frontal lobe of schizophrenic patients with high scores on the Scale for the Assessment of Negative Symptoms (SANS).

The symptom structure of panic disorder : a trial using factor and cluster analysis

Using cluster analysis of 207 patients with panic disorder (PD), we investigated the relationships between several panic symptoms at the time of panic attacks, which included anticipatory anxiety, agoraphobia, and 13 clinical symptoms based on the Diagnostic and Statistics Manual‐III‐Revised. Cluster analysis revealed three panic symptom clusters: cluster A (dyspnea, choking, sweating, nausea, flushes/chills); cluster B (dizziness, palpitations, trembling or shaking, depersonalization, agoraphobia, and anticipatory anxiety); and cluster C (fear of dying, fear of going crazy, paresthesias, and chest pain or discomfort). Generally, cluster A was comprised exclusively of physiological symptoms, among which respiratory symptoms were prominent, cluster B included both panic and non‐panic symptoms such as agoraphobia and anticipatory anxiety, and cluster C was comprised chiefly of fear symptoms.