Jun Murashita

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.

Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders

Abstract Proton magnetic resonance spectra were recorded from a subcortical region containing the basal ganglia in 40 patients with affective disorders (18 with bipolar disorder and 22 with major depression) and in 20 normal controls. The absolute concentration of the choline-containing compounds (Cho) in the patients with bipolar disorder in the depressive state was significantly higher than that in the normal controls. The patients with bipolar disorder had significantly higher levels of the Cho/creatine + phosphocreatine (Cr) and Cho/N-acetly-l-aspartate (NAA) peak ratio compared with the normal controls in both the depressive and euthymic states, with a tendency to higher levels in the depressive state. The Cho/NAA peak ratio was also significantly higher in the patients with major depression compared with the normal controls. These results suggest that the membrane phospholipid metabolism in the basal ganglia is altered in affective 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.

Reduced intracellular pH in the basal ganglia and whole brain measured by 31P-MRS in bipolar disorder.

Abstract  The authors have previously reported that intracellular pH measured by phosphorus‐31 magnetic resonance spectroscopy (31P‐MRS) was decreased in the frontal lobes of patients with bipolar disorder. In the present study, phosphorus metabolism in the basal ganglia was examined in 13 patients with bipolar disorder and 10 matched controls by localized 31P‐MRS. While no significant alteration of peak area ratios was found for all phosphorus metabolites, intracellular pH was significantly reduced in the basal ganglia in patients with bipolar disorder (7.014 ± 0.045) compared with control subjects (7.066 ± 0.047, P < 0.05). Unexpectedly, non‐localized 31P‐MR spectra also showed significantly lower levels of intracellular pH (6.970 ± 0.025) than controls (6.986 ± 0.024, P < 0.05). These results suggest that decreased intracellular pH in the brain of patients with bipolar disorder is not caused by dysfunction of the frontal lobes but reflect altered metabolism at the cellular level.

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.

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.

Prevalence of cavum septum pellucidum detected by MRI in patients with bipolar disorder, major depression and schizophrenia

The incidence of cavum septum pellucidum (CSP), which has been widely regarded as a developmental anomaly of little clinical importance in neuropathology, was examined in 113 patients with affective disorders (69 with bipolar disorder and 44 with major depression), 40 schizophrenic patients, and 92 control subjects by magnetic resonance imaging (MRI). Significantly higher incidence of Grade 3-4 CSP (moderate to large) compared with the controls was found only in the schizophrenics. When a broader interpretation of CSP, including indeterminant (Grade 1) and small (Grade 2) CSP was used, three additional patients with bipolar disorder were found to have Grade 1-2 CSP, and the total prevalence of Grade 1-4 CSP in the patients with bipolar disorder was significantly higher than that in the control subjects but slightly lower than that in the schizophrenic patients. CSP was not observed in any patient with major depression. There were no differences between the patients with and without CSP in age, sex, education, or the duration of illness. These findings are consistent with the hypothesis that neurodevelopmental abnormality may be present in schizophrenia, and such an abnormality may also be present in some patients with bipolar disorder.

Altered brain energy metabolism in lithium-resistant bipolar disorder detected by photic stimulated 31P-MR spectroscopy.

BACKGROUND Previous 31P-MRS (magnetic resonance spectroscopy) studies suggested altered brain energy metabolism in bipolar disorder. This study characterized brain energy metabolism in lithium-resistant bipolar disorder using the photic-stimulation paradigm. METHODS Subjects were 19 patients with DSM-IV bipolar disorder (nine responders and 10 nonresponders, 13 with bipolar I and six with bipolar II) in the euthymic state and 25 healthy volunteers. Energy metabolism in the occipital region was examined by 31P-MRS during photic stimulation (PS). Six 31P-MR spectra were obtained, one was before PS (Pre), two during 12 min of PS (PS1, PS2), and three after the PS (Post 1, Post 2, Post 3). RESULTS Significant effect of diagnosis (lithium-responsive bipolar disorder, lithium-resistant bipolar disorder, and control) was found for the phosphocreatine peak area ratio during the course of the photic stimulation (P < 0.05 by repeated measures ANOVA). The phosphocreatine peak area ratio was significantly decreased at Post 1 and Post 2 compared with Pre in lithium-resistant bipolar patients (P = 0.01 and P = 0.01 by Dunnetts multiple comparison). CONCLUSIONS The finding that phosphocreatine decreased after photic stimulation may be compatible with mitochondrial dysfunction. It is possible that mitochondrial function is impaired in lithium-resistant bipolar disorder.