Nobutoshi Kawai

High-dose of multiple antipsychotics and cognitive function in schizophrenia: The effect of dose-reduction

We evaluated the effect of antipsychotic dose-reduction on the neurocognitive function of 17 schizophrenic patients (11 male and 6 female, mean age=42.4+/-11.3) who have been taking high-doses of multiple conventional antipsychotics. The mean (+/-SD) of total daily antipsychotic doses (in mg/day, chlorpromazine-equivalent) was 2,253 (+/-668) at baseline, which was reduced to 1,315 (+/-276). Possible changes in neurocognitive function were assessed using Wisconsin card sorting test (WCST) and continuous performance test (CPT). As controls, we examined WCST and CPT in 6 schizophrenic patients (4 male and 2 female, mean age=47.7+/-14.2) who had been taking high-doses of multiple antipsychotics (mean daily antipsychotic dose=1,753+/-165 mg) and declined to change their antipsychotic regimen. In WCST, the mean number of total correct answers significantly increased (53.2+/-16.3 vs. 63.8+/-19.6, P=0.035, Wilcoxon signed rank test); perseverative errors significantly decreased (54.4+/-27.3 vs. 35.4+/-20.1, P=0.013, Wilcoxon signed rank test) after the antipsychotic dose-reduction. In contrast, the control group showed no significant difference between the two WCST performances conducted with a three-month interval. The improvements in WCST performance significantly correlated with the decreases in PANSS negative syndrome score in the subject patients. No significant change was observed in CPT performances in either group. Our preliminary data shows that, in schizophrenic patients taking high-doses of multiple conventional antipsychotics, dose-reduction might lead to improvements in cognitive functions.

Risperidone failed to improve polydipsia-hyponatremia of the schizophrenic patients

Abstract The effect of risperidone on polydipsia‐hyponatremia was evaluated in six hospitalized schizophrenic patients. The normalized diurnal weight gain (NDWG), urine‐specific gravity (USG), urine and plasma osmolarity, and serum sodium were monitored during 9 months of risperidone treatment. The dose of risperidone (mean ± SD = 8.0 ± 1.0, range = 6–9 mg/day) was determined as approximately half of the haloperidol‐equivalent dose of previous neuroleptics. Before risperidone treatment, the mean (± SD) BPRS score was 23.5 ± 7.1; no significant improvement was observed after risperidone (22.0 ± 7.5). The subjects showed relatively high serum prolactin before risperidone treatment (mean ± SD = 16.5 ± 9.7 ng/mL), that was not significantly decreased by risperidone (14.2 ± 7.9 ng/mL). The monthly means (± SD) of NDWG and USG before risperidone were 5.5 ± 1.5 (%) and 1.002 ± 0.001, respectively. These and other indices did not significantly improve throughout the study period. Although the sample size is relatively small, our preliminary data showed that risperidone might not be effective on polydipsia‐hyponatremia of schizophrenic patients.

CT, MR, and spect findings in a general paresis

CNS changes in a case with general paresis were investigated by X-ray computed tomography (CT), Magnetic resonance (MR), and single photon emission computed tomography (SPECT). CT and MR showed a mild degree of diffuse cortical atrophy and the dilatation of lateral ventricles with no signs of ischemic lesions or inflammations. On the other hand, SPECT using 123I-N-isopropyl-p-iodoamphetamine (123I-IMP demonstrated marked reduction of the cerebral blood flow especially in the bilateral frontal and temporal cortices. Moreover, the reduction of the blood flow was significantly improved after the antisyphilitic therapy, correlated with the improvement of the mental disorders. These observations suggested that the SPECT is a useful method to evaluate the brain dysfunctions, and to assess the effect of antisyphilitic therapy in the patients with general paresis.

Autoradiographic localization of CCK-8 binding sites in the rat brain: Effects of chronic methamphetamine administration of these sites

The effects of chronic methamphetamine (MAP) administration (at a dose of 4 mg/kg for 14 days) on [3H]pCCK-8 binding sites in the rat brain were investigated by an in vitro quantitative receptor autoradiographic technique. The number of [3H]pCCK-8 binding sites was significantly reduced in layers III and IV of the medial frontal, anterior, and posterior cingulate cortices, in layers II-IV of the retrosplenial cortex, in layers III-VI of the dorsal insular cortex, and in the reticular nucleus of the thalamus, compared to these numbers in a control group of rats that received physiologic saline. Further, chronic methamphetamine administration led to a significant increase in the number of these binding sites in layer I of the entorhinal cortex. These findings indicate the CCK peptides in the limbic lobe may be closely related to the development of the behavioral changes associated with methamphetamine sensitization. In addition, these results provide supporting evidence for the involvement of the limbic system in the pathophysiology of schizophrenia.

CNS changes in neuro-Behçet's disease : CT, MR, and SPECT findings

CNS changes in three cases of neuro-Behçets disease were observed by computed tomography (CT), magnetic resonance (MR) and single photon emission computed tomography (SPECT). The present study illustrates the reversibility of lesions in the brain stem with MR, while CT failed to show any abnormal findings in the region of the disease. We conclude that MR is a quite useful method to detect lesions in the brain stem and to evaluate the effects of treatment in neuro-Behçets disease. SPECT is also an important method for the evaluation of dementia recognized in neuro-Behçets disease.

Chronic herpes simplex encephalitis with somnambulism : CT, MR and SPECT findings

Abstract: A 64‐year‐old male with herpes simplex encephalitis had shown somnambulism and memory disturbance for nine months before consciousness disturbance appeared. Brain CT, MR and SPECT revealed lesions in the right temporal lobe. The atypical clinical course of this patient, including chronkity and focal symptom, is discussed.

Behavioral effects of phencyclidine and its major metabolite, (trans)4-phenyl-4-(1-piperidinyl)cyclohexanol, in mice.

To elucidate the biological activity of natural metabolites of phencyclidine (PCP), we examined the behavioral effects of a major metabolite, the trans isomer of 4-phenyl-4-(1-piperidinyl)cyclohexanol [(trans)PPC], in mice, (Trans)PPC caused dose-related increase in locomotor activity and rearing in mice when injected intraperitoneally at the doses ranging from 10 to 30 mg/kg. (Trans)PPC at any dose tested failed to produce swaying and falling. On the other hand, PCP at the doses ranging from 1 to 10 mg/kg caused swaying and falling as well as hyperlocomotion in a dose-related manner. These indicate that unlike PCP, hyperlocomotion and rearing may be the predominant behavioral responses to (trans)PPC in the 10-30 mg/kg dose range. Furthermore, it is feasible to surmise that not only PCP but also its major metabolite (trans)PPC is involved in psychotic reactions produced by PCP.

Effect of methamphetamine and dopamine receptor antagonists on cholecystokininlike immunoreactivity in the rat medial prefrontal cortex

A single intraperitoneal administration of methamphetamine (MAP) reduces cholecystokininlike immunoreactivity (CCK-LI) in medial prefrontal cortex (mPFC) of the rat brain. This report examines the effects of various dopamine (DA) receptor antagonists [haloperidol (HAL), sulpiride (SUL), YM09151-2 (YM), and SCH23390 (SCH)] on MAP-induced abnormal behaviors and the changes of CCK-LI in the rat mPFC. A single subcutaneous administration of HAL (0.25 mg/kg), YM (0.1 mg/kg), or SUL (250 mg/kg) significantly reduced the basal CCK-LI in mPFC by 20-40%; a selective D1 antagonist, SCH (up to 1.0 mg/kg), had no effect on basal CCK-LI. However, the reduction of CCK-LI induced by MAP (20-40%) was abolished by the pretreatment with HAL (0.025 and 0.25 mg/kg), YM (0.01 and 0.1 mg/kg), or SCH (1.0 mg/kg), without being affected by SUL (up to 250 mg/kg). This effect of DA antagonists on MAP-induced change in CCK-LI was associated with an inhibition of MAP-induced stereotyped behaviors. These data suggest that the CCK-containing neurons in rat mPFC are functionally related to the mesocortical DA system and may participate in a development of abnormal behaviors induced by MAP.

A relationship between urine specific gravity and hyponatremia in hospitalized schizophrenic patients

The relationship between urine specific gravity (USG) and the incidence of polydipsia/hyponatremia in hospitalized schizophrenic patients was examined. On the basis of five independent USG values, we identified 49% (35 out of 72) of male and 22% (8 out of 37) of female patients with hyposthenuria (mean USG < or = 1.008). Review of 2 years of records of routine laboratory examinations identified 12 males with hyponatremia, 11 males with borderline hyponatremia, and 49 males with normal values; among female patients, only one patient with hyponatremia and three patients with borderline values were identified. A significantly lower mean USG (1.003 +/- 0.001) for the male patients with hyponatremia compared with the male patients with normal serum sodium data (1.011 +/- 0.005) was observed. All of the male patients with hyponatremia, as well as 18 of the 49 male patients with normal serum sodium values, exhibited hyposthenuria. The USG values of all the patients with hyponatremia were consistently quite low (< or = 1.005), whereas 14 of the 18 normonatremia/hyposthenuria patients had normal USG values (i.e. > or = 1.009) in at least one of five determinations; the mean USG values for most (16 of 18) of the normonatremia/hyposthenuria patients ranged from 1.006 to 1.008. Thus, many hospitalized schizophrenic patients exhibit hyposthenuria of varying degrees, but consistently low USG values are most suggestive of the risk of polydipsia/hyponatremia.