Shiro Totsuka

Clinical Evaluation of Attention-Deficit Hyperactivity Disorder by Objective Quantitative Measures

This study assessed the diagnostic potential of the actigraph, the Continuous Performance Test, and the Matching Familiar Figures Test in diagnosing attention-deficit hyperactivity disorder (ADHD). Twenty boys previously diagnosed with ADHD and 52 controls were examined. By these measures the boys with ADHD were differentiated from the controls with sensitivity and specificity above 75%. We were able to classify ADHD into eight subtypes by combining the scores of the actigraph and the CPT: “hyperactive-impulsive”, “hyperactive-inattentive”, “impulsive-inattentive”, “hyperactive”, “impulsive”, “inattentive”, “mixed”, and “unspecified” type. These classifications may be useful in diagnosing ADHD.

Correlation of regional cerebral blood flow with performance on neuropsychological tests in schizophrenic patients

Regional cerebral blood flow (rCBF) was determined by the 133Xe inhalation technique (Headtome II: ring detection SPECT) in 53 DSM-III schizophrenic patients. The rCBF values were corrected by using end-tidal carbon dioxide concentration values (PECO2). After rCBF measurement, neuropsychological tests--Word Fluency Test, Maze Test and Wisconsin Card Sorting Test--were performed. There were significant correlations between frontal rCBF and scores on each neuropsychological test. In particular, a moderate correlations between the frontal rCBF and the performance on the Wisconsin Card Sorting Test was noted. It seems likely that decrease of rCBF in prefrontal regions at rest reflects a disturbance of frontal lobe function in schizophrenic patients.

Changes in regional brain activity in major depression after successful treatment with antidepressant drugs

Relative regional cerebral blood flow was measured with single photon emission computed tomography (SPECT) using 99mTc‐hexamethyl‐propyleneamine oxime (99mTc‐HMPAO) in 16 patients with major depression while they were in the depressed state as well as in remission. All patients were closely matched with regard to medication status. In the depressed state, significant reductions in tracer uptake were found in the left superior frontal, bilateral parietal and right lateral temporal cortex. During remission, significant increases in uptake were found in the left superior frontal, right parietal and right lateral temporal cortex. There were no significant differences in tracer uptake between patients in remission and controls. These findings suggest that the regional decreases in tracer uptake observed in the depressed state might be a state‐related abnormality.

The binding of basic fibroblast growth factor to Alzheimer's neurofibrillary tangles and senile plaques

Brain sections from Alzheimers disease (AD) patients and controls were treated with basic fibroblast growth factor (bFGF) and then immunostained with anti-bFGF. Additional sections were treated with biotinylated bFGF without using the anti-bFGF. Labelling was visualized by the ABC method. Both protocols above intensely labelled neurofibrillary tangles, senile plaques and amyloidotic vessels in AD brains. Omission of the bFGF treatment abolished the staining of the AD lesions. The pretreatment of sections with heparitinase also reduced their staining. These results indicate that AD lesions contain bFGF-binding sites and that the chemical substrate for bFGF binding to AD lesions was heparan sulfate.

Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy

Abstract  The relationship between the genetic polymorphism of S‐mephenytoin 4′‐hydroxylation catalyzed by CYP2C19 and the N‐demethylation of imipramine was examined in 10 Japanese depressed patients. Five patients, who were poor metabolizers of S‐mephenytoin, were determined to be either homozygous for a mutation in exon 5 or heterozygous for mutations in exon 4 and exon 5 of the CYP2C19 gene. In contrast, five patients, who were extensive metabolizers, had no mutations. The demethylation index (the desipramine/imipramine ratio) was significantly lower in patients with genetic defects. Plasma levels of imipramine and 2‐hydroxyimipramine normalized by the daily dose (mg) per weight (kg) were significantly higher in patients with genetic defects. This suggests that the N‐demethylation of imipramine is impaired in patients with genetic defects in the CYP2C19 gene, and that genotype determination may be useful in preventing side effects induced by unexpectedly elevated levels of imipramine.

An epidemiological study of eating disorders in a northern area of Japan

Nadaoka T, Oiji A, Takahashi S, Morioka Y, Kashiwakura M, Totsuka S. An epidemiological study of eating disorders in a northern area of Japan.

Acetylcholinesterase activities and monoamine metabolite levels in the cerebrospinal fluid of patients with alzheimer's disease

We measured cholinesterase (ChE) activity and monoamine metabolite levels in the cerebrospinal fluid (CSF) of 22 patients with early-onset Alzheimer type dementia (Alzheimers disease; AD) and of 32 controls. Acetylcholinesterase (AChE) activity, 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels were significantly lower in AD patients than in controls. However, there was an overlap in values of each CSF parameter. The measurement of various CSF parameters rather than one alone was more useful as a diagnostic aid. CSF ChE activities correlated with scores on the GBS rating scale, Hasegawa dementia scale, and Wechsler Adult Intelligence Scale, but the monoamine metabolite levels did not. Although cholinergic and monoaminergic deficits may coexist in AD patients, cholinergic deficits tend to be more often associated with cognitive decline than the monoaminergic deficits.

Stress and psychiatric disorders in local government officials in Japan, in relation to their employment level

In order to explore an association between psychiatric disorders and employment level, 283 local government officials in Japan were asked to complete a questionnaire consisting of a series of psychometric scales. The Daily Hassles Scale, General Health Questionnaire and Burnout Scale were used to measure stress, psychiatric disorders and burnout syndrome, respectively. As a result of canonical correlation analysis, the first canonical correlation indicated that the higher the level of stress under poorer support systems, the greater the likelihood of burnout syndrome. The second canonical correlation indicated that the stronger the support system, the smaller the tendency toward depression. Officials in higher levels of employment were supported less and were more severely depressed than officials at lower levels of employment.

Enhancement of 5-hydroxytryptamine-stimulated phosphoinositide hydrolysis in the rat cerebral cortex by repeated immobilization stress.

The present study was undertaken to investigate the influence of repeated immobilization stress on phosphoinositide hydrolysis induced by 5-hydroxytryptamine (5-HT) and noradrenaline in the rat cerebral cortex. Three groups of rats subjected to stress intervention were immobilized for 2 h per day for 3, 7, and 14 days. The stress intervention of any duration did not alter noradrenaline-stimulated phosphoinositide hydrolysis. The 3- and 7-day repeated immobilization enhanced 5-HT-stimulated phosphoinositide hydrolysis, whereas the characteristics of 5-HT2 receptor binding did not change. Chronic treatment with imipramine partially, but significantly, suppressed the increase in 5-HT-stimulated phosphoinositide hydrolysis, induced by the 3-day repeated immobilization. These findings imply that modulation of 5-HT-stimulated phosphoinositide hydrolysis occurs in stressful situations and that the therapeutic effects of tricyclic antidepressant drugs might be related to the modulation of phosphoinositide hydrolysis mediated by 5-HT receptors.