Mitsumoto Sato

A Lasting Vulnerability to Psychosis in Patients with Previous Methamphetamine Psychosis

Chronic MAP abuse may produce a lasting vulnerability of the brain which leads to a paranoid delusional psychosis with hallucinations similar to schizophrenia. This view is based on the clinical observations that duration of the psychotic episodes could last quite long after excretion of MAP in the urine, and that reuse of MAP, alcohol ingestion and nonspecific psychological stressors lead to acute recurrence of psychotic episodes whose clinical features are almost identical to the initial episode in patients with prior MAP psychosis. The experimental studies indicate that a lasting change at the nerve terminal membranes, namely transporters of MAP and dopamine at the uptake sites, in the striatum and nucleus accumbens may be a cause for induction and expression of stimulant-induced sensitization, which may relate to vulnerability to schizophrenia-like psychotic episodes in MAP psychosis.

Regional cerebral blood flow abnormalities in late‐life depression:Relation to refractoriness and chronification

Abstract We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and (99mTc‐hexamethyl‐propylenamine oxime (99mTc‐HMPAO). Compared with 13 age‐matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non‐refractory subgroup. In the non‐refractory subgroup, rCBF decreased significandy in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late‐life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression.

Centrally acting histamine H1 antagonists promote the development of amygdala kindling in rats

We studied the effect of histamine H1 antagonists on the development of amygdala kindling, an experimental model of epilepsy, in rats. The centrally acting histamine H1 antagonists including pyrilamine (mepyramine) and ketotifen showed an acceleration in the rate of electrical stimulation to develop fully kindled convulsive seizures. On the contrary, epinastine, a histamine H1 antagonist which scarcely enters the brain, showed no acceleration. These findings suggest that the central histaminergic neuron system plays an inhibitory role on the seizure development through central histamine H1 receptors.

Effects of histamine agents on methamphetamine-induced stereotyped behavior and behavioral sensitization in rats

Abstract In this study, effects of histamine (HA) agents on methamphetamine (METH)-induced stereotyped behavior and behavioral sensitization were examined in rats. Pretreatment with a precursor of HA, L-histidine (750 mg/kg), significantly inhibited the METH (3 mg/kg)-induced stereotyped behavior, whereas pretreatment with an inhibitor of HA synthesis, α-fluoromethylhistidine (FMH) (100 mg/kg), an H1 antagonist pyrilamine (5 mg/kg) or an H2 antagonist zolantidine (5 mg/kg) enhanced it. The inhibitory effect of L-histidine on METH-induced stereotyped behavior was significantly blocked by coadministration of pyrilamine and zolantidine, indicating that the effect is mediated through H1 and H2 receptors. Moreover, chronic treatment with METH (3 mg/kg) significantly enhanced stereotyped behavior at the rechallenge with METH (1 mg/kg). Chronic treatment with L-histidine (750 mg/kg) plus METH inhibited the METH-induced argumentation of stereotyped behavior, while that with FMH (100 mg/kg), pyrilamine (5 mg/kg) or zolantidine (5 mg/kg) potentiated it. These findings suggest that the HA neuron system has an inhibitory role in METH-induced stereotyped behavior and behavioral sensitization.

Changes in regional cerebral blood flow abnormalities in late‐life depression following response to electroconvulsive therapy

Abstract The impact of electroconvulsive therapy (ECT) on the regional cerebral blood flow (rCBF) abnormalities in late‐life depression is still unknown and the clinical significance of these findings in late‐life depression has not been fully discussed. Using single photon emission computed tomography (SPECT) with 99mTc‐hexamethylpropylene amine oxime (99mTc‐HMPAO), we examined the changes of rCBF patterns in nine late‐life patients with major depressive episodes before and following response to ECT compared with nine age‐ and sex‐matched healthy volunteers. Statistical comparisons were made on both region‐of‐interest (ROI) and voxel‐by‐voxel bases. In ROI‐based analyses, a mean rCBF was significantly decreased in the patients before ECT compared with the control, significantly increased (normalized) in the patients 2 weeks after ECT compared with that before ECT, and still increased in the patients 12 weeks after ECT compared with that before ECT. In voxel‐by‐voxel analyses, a significant rCBF reduction was found in the bilateral pre‐ and subcallosal anterior cingulate cortex, the bilateral caudal orbitofrontal cortex, the right insular cortex and the right posterior middle frontal gyrus in patients before ECT compared with the control, and similar rCBF patterns were shown at 2 weeks and 12 weeks after ECT. We propose the hypothesis that a mean rCBF reduction may have a state‐related property while persistent anterior paralimbic hypoperfusion may have a trait‐like property, which relates to the relapse vulnerability as well as a tendency toward medication failure and illness chronicity in late‐life depression.

Effects of the acute and chronic restraint stresses on the central histaminergic neuron system of Fischer rat.

The effects of acute and chronic restraint stresses on the brain histamine level and histamine N-methyltransferase activity in Fischer rat brain were studied. The acute restraint stress increased the histamine levels in the diencephalon and nucleus accumbens, and increased the histamine N-methyltransferase activities in the nucleus accumbens and striatum. The chronic restraint stress also increased histamine N-methyltransferase activities in the nucleus accumbens and striatum. These results indicate that the acute and chronic restraint stresses increase the brain histamine turnover, which may partly relate to the vulnerability for stress-induced anxiety and depression.

Name Change for Schizophrenia

Psychiatric disorders carry a stigma that usually leads to discrimination and resulting problems in many walks of life. People with mental illness thus have difficulties getting a job, finding housing, and making (or keeping) friends or partners. The stigma adds misery to the life of persons with a mental disorder. It affects their families as well as professionals and others who provide them with care.

Tc-99m HMPAO SPECT in the evaluation of Alzheimer’s disease: correlation between neuropsychiatric evaluation and CBF images

The purpose of this study was to evaluate the effects of various covariants on the distribution pattern of Tc-99m HMPAO in patients with Alzheimer’s disease by correlation analysis. Twenty patients with Alzheimer’s disease and 15 age matched normal subjects participated. Tc-99m HMPAO brain SPECT and xray computed tomography (CT) were acquired for each subject. SPECT images were transformed to a standard size and shape by automated image registration (AIR) and were used for group comparison by means of SPM96. Voxel based covariance analysis was performed on standardised images taking the age of patients, severity of disease (clinical dementia rating scale, mini mental state examination, physical self maintenance scale), and atrophy indices as variables. There was significantly decreased regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal regions in the patient group (p<0.001), more marked in those patients having severe dementia. Covariance analysis disclosed that aging and severity of disease have a pronounced effect on rCBF, especially that of the left parietal region.

Smooth pursuit eye movements and express saccades in schizophrenic patients

Abnormalities of saccades such as disinhibition have been hypothesized as one cause of smooth pursuit eye movement (SPEM) dysfunctions in schizophrenia. Thus, we studied saccadic eye movements in schizophrenics with SPEM dysfunction. Subjects were divided into three groups: 10 normal control subjects, 10 schizophrenic subjects without SPEM dysfunction and 10 schizophrenic subjects with SPEM dysfunction characterized by a cogwheel appearance. Visually guided saccades in gap and overlap paradigms (Saslow, 1967) were examined and saccadic reaction times (SRTs) were measured in all subjects. Only schizophrenics with SPEM dysfunctions tended to manifest excessive reflexive saccades, named express saccades (Fischer, 1987), in the gap paradigm. Moreover, most of them were also found to have express saccades in the overlap paradigm, whereas normal subjects and schizophrenic subjects without SPEM dysfunction did not show such phenomena under the same conditions. In particular, most express saccades in the overlap paradigm in schizophrenics with SPEM dysfunction, were found in movements to the right.

Smooth Pursuit Eye Movements and Voluntary Control of Saccades in the Antisaccade Task in Schizophrenic Patients

Abstract: It has been hypothesized that a saccade control dysfunction is one cause of a smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. We studied the voluntary control of saccades in schizophrenic patients with the SPEM dysfunction using an antisaccade task. The mean error rate in the antisaccade task was significantly higher in the two schizophrenic groups with and without a SPEM dysfunction than in the normal control group. Furthermore, the schizophrenic group with the SPEM dysfunction showed significantly more errors than the schizophrenic group without the SPEM dysfunction. These findings seem to suggest a close relationship between the SPEM dysfunction and the appearance of errors which indicates an inability to inhibit reflexive saccades voluntarily in the antisaccade task. However, 4 of 10 subjects with the SPEM dysfunction showed an error rate less than the mean error rate of the schizophrenic group without the SPEM dysfunction. So, a voluntary control disorder of saccades as the main cause of the SPEM dysfunction appeared to be unlikely. An interesting finding of this study was that many schizophrenic subjects with the SPEM dysfunction showed errors with the latencies similar to those in express saccades2, particularly in the rightward direction. This finding may suggest a close relationship between the SPEM dysfunction in schizophrenic patients and some pathological conditions of express saccades such as disinhibition of express saccades.