Effects of lithium on brain glucose metabolism in healthy men.

Lithium is clinically available for the treatment of mood disorders. However, it has remained unclear how lithium acts on the brain to produce its effects. The aim of this study was to evaluate the effects of chronic lithium on human brain activity using positron emission tomography and clarify the correlation between brain activity changes and cognitive functional changes as induced by chronic lithium administration. A total of 20 healthy male subjects (mean age, 32 +/- 6 years) underwent positron emission tomographic scans with F-fluorodeoxyglucose and a battery of neuropsychological tests at baseline condition and after 4 weeks of lithium administration. Brain metabolic data were analyzed using statistical parametric mapping. Lithium increased relative regional cerebral glucose metabolism (rCMRglc) in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased rCMRglc in the right cerebellum and left lingual gyrus/cuneus. There was no difference in any of the variables of cognitive functions between the baseline condition and after chronic lithium administration. There was no correlation between rCMRglc changes in any of the brain regions and individual variable changes in any of the neuropsychological tests. The results suggest that the effects of chronic lithium are associated with increased activity in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased activity in the right cerebellum and left lingual gyrus/cuneus.

Left temporal perfusion associated with suspiciousness score on the Brief Psychiatric Rating Scale in schizophrenia.

We evaluated the relationship between regional cerebral blood flow (rCBF) and clinical symptoms in patients with schizophrenia. Single photon emission computed tomography with N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was used to study 29 patients with schizophrenia. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). We examined the correlation between rCBF and each BPRS item score using Statistical Parametric Mapping software. Corrected P-values < 0.05 were considered as statistically significant. The suspiciousness score on the BPRS was positively correlated with rCBF in the left inferior temporal gyrus. There was no significant correlation between rCBF and any other items of the BPRS. There was no significant correlation between rCBF and chlorpromazine-equivalent dosage. This analysis permits the quantitative assessment of the severity of persecutory delusions in relation to left temporal perfusion in patients with schizophrenia.

Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic brain injury without MRI abnormality in the chronic stage.

PURPOSE: Traumatic brain injury (TBI) causes brain dysfunction in many patients. However, some patients have severe brain dysfunction but display no abnormalities on magnetic resonance imaging (MRI). There have been some reports of hypometabolism even in such patients. The purpose of this study was to investigate the relationship between metabolic abnormality and loss of neuronal integrity in TBI patients with some symptoms but without MRI abnormalities. METHODS: The study population comprised ten patients with TBI and ten normal volunteers. All of the patients were examined at least 1 year after the injury. ( 15)O-labelled gas PET and [(11)C]flumazenil (FMZ) positron emission tomography (PET) were carried out. The cerebral metabolic rate of oxygen (CMRO(2)) and binding potential (BP) images of FMZ were calculated. Axial T2WI, T2*WI and FLAIR images were obtained. Coronal images were added in some cases. RESULTS: All of the patients had normal MRI findings, and all showed areas with abnormally low CMRO(2). Low uptake on BP images was observed in six patients (60%). No lesions that showed low uptake on BP images were without low CMRO(2). On the other hand, there were 14 lesions with low CMRO(2) but without BP abnormalities. CONCLUSION: These results indicate that there are metabolic abnormalities in TBI patients with some symptoms after brain injury but without abnormalities on MRI. Some of the hypometabolic lesions showed low BP, indicating a loss of neuronal integrity. Thus, FMZ PET may have potential to distinguish hypometabolism caused by neuronal loss from that caused by other factors.

[Treatment of "the premonitory state of schizophrenia" with atypical antipsychotics].

"Premonitory symptoms and signs" before the full-blown stage of schizophrenia are recognized as abnormal expressions (signs) and symptoms of "early schizophrenia", as described by Nakayasu (1990). The following conclusions were derived from my examination of the effects of atypical antipsychotics on six patients suffering from 'the premonitory symptoms and signs' in 'the premonitory state of schizophrenia'. 1) Even though hyperventilation, fatigue and a depressive state existed in the foreground at the first medical examination, we suspected 'the premonitory state of schizophrenia', and investigated symptoms of 'early schizophrenia' as described by Nakayasu, in cases in which abnormal expressions such as stiff facial expression and specific tense and perplexed attitude were observed. 2) In cases in which 'the premonitory symptoms and signs' were observed, we introduced treatment with atypical antipsychotics as soon as possible. Hyperventilation and a depressive state, which were considered to be induced by 'the premonitory state of schizophrenia', disappeared as a result of the improvement of 'the premonitory symptoms and signs' by the atypical antipsychotics. 3) Risperidone, perospirone, and olanzapine were effective for so-called "positive early symptoms". Risperidone, which is expected to have an acute effect, was effective in cases in which early intervention was necessary. When a depressive state was secondarily induced by risperidone, a change to perospirone was useful. Furthermore, when risperidone and perospirone were not sufficiently effective, olanzapine improved 'the premonitory symptoms and signs'. 4) In cases in which so-called "negative early symptoms" and a decrease in the energy-potential, such as emotional blunting, were observed, olanzapine induced improvement. 5) In 'the premonitory state of schizophrenia', treatment with atypical antipsychotics should be maintained, for both the improvement of 'the premonitory symptoms and signs' and the prevention of progression to the full-blown stage. The dose and duration of the treatment with antipsychotics should be carefully modified, with consideration for the specificity of the life cycle and life events for each patient. In conclusion, treatment with atypical antipsychotics was useful for both the improvement of 'the premonitory symptoms and signs of schizophrenia' and the prevention of the development of pathogenesis.

A prospective, open-label, flexible-dose study of quetiapine in the treatment of delirium.

BACKGROUND: Delirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impaired cognitive functioning. High-potency typical neuroleptics have traditionally been used as first-line drugs in the treatment of delirium. However, these drugs are frequently associated with undesirable adverse events including extrapyramidal symptoms (EPS). The purpose of the present open-label, flexible-dose study was to provide preliminary data on the usefulness and safety of quetiapine for patients with delirium. METHOD: Twelve patients with DSM-IV delirium were treated with flexible doses of open-label quetiapine (mean +/- SD dosage = 44.9 +/- 31.0 mg/day). To evaluate the usefulness and safety of quetiapine, scores from the Delirium Rating Scale, Japanese version, were assessed every day (for 1 outpatient, at least twice per week), and scores from the Mini-Mental State Examination, Japanese version, and the Drug-Induced Extrapyramidal Symptom Scale were assessed at baseline and after remission of delirium. Data were gathered from April to October 2001. RESULTS: All patients achieved remission of delirium several days after starting quetiapine (mean +/- SD duration until remission = 4.8 +/- 3.5 days). Quetiapine treatment was well tolerated, and no clinically relevant change in EPS was detected. CONCLUSION: Quetiapine may be a useful alternative to conventional neuroleptics in the treatment of delirium due to its rapid onset and relative lack of adverse events. Further double-blind, placebo-controlled studies are warranted.