A placebo controlled trial of remoxipride in the prevention of relapse in chronic schizophrenia

Sixty-two DSM III chronic schizophrenic inpatients were selected for a double-blind, placebo controlled, multi-centre, relapse prevention study of remoxipride, a selective dopamine (D₂)-receptor antagonist. After a 1 month placebo washout, 23 patients had relapsed and were withdrawn. Of the remaining patients 19 were randomised to remoxipride (150–300 mg daily) and 20 to placebo. Their median age was 58 years, 26 were male, and the median duration of illness was 33 years. After 24 weeks a further total of 8 remoxipride and 17 placebo patients had been withdrawn. Excluding three patients withdrawn for reasons other than relapse, the comparative relapse rates were 37% and 75%, respectively (P=0.015). Efficacy analyses using clinical global impression (P=0.04) and change in BPRS scores (P=0.016) were in favour of remoxipride. Extrapyramidal symptoms were minimal in both groups. Treatment emergent adverse events were similar in the two groups. Remoxipride is therefore of potential value as a safe drug which is both effective and well tolerated in the long term management of chronic schizophrenic patients.     

Ventricular enlargement, clinical correlates and treatment outcome in chronic schizophrenic inpatients.

The ventricle-brain ratio (VBR) of 42 chronic schizophrenic patients was compared with that of 42 age-matched medical controls. For the schizophrenics, the relationship of various clinical parameters to the VBR was assessed, and the outcome of 12 weeks of double-blind treatment with either risperidone or haloperidol. The results confirm that schizophrenic patients have slightly enlarged lateral ventricles compared with medical controls. Only for schizophrenics, an effect of age, but not of duration of illness, was noticed. This study does not support the validity of a clinical subdivision of chronic schizophrenic patients on the basis of the VBR. Neither negative, positive nor general psychopathological symptoms, as measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), were related to the VBR, nor were abnormal involuntary movements or extrapyramidal symptoms. No association between season of birth or a family history of major mental disorder and VBR could be demonstrated. Treatment response was predicted by the total PANSS score and the PANSS general psychopathology subscale score at baseline. There was a trend for patients with higher VBR to have a more or haloperidol). or haloperidol).     

Endogenous kynurenic acid disrupts prepulse inhibition.

BACKGROUND: Recent studies show that endogenous levels of kynurenic acid (KYNA) are increased in the cerebrospinal fluid of schizophrenic patients. Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating that is reduced in neuropsychiatric disorders, such as schizophrenia. Previous studies show that administration of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine or MK-801, leads to deficits in sensorimotor gating that mimic those observed in schizophrenic patients. METHODS: The present study examined the effects of the endogenous NMDA receptor antagonist KYNA on startle and PPI in rats. Elevation of endogenous brain levels of KYNA was achieved through intraperitoneal (IP) administration of kynurenine (100 mg/kg), the precursor of KYNA, or by intravenous administration of PNU 156561A (10 mg/kg). RESULTS: A fourfold increase in brain KYNA levels, as induced by kynurenine or PNU 156561A, significantly reduced PPI. There were no differences in startle magnitudes between control rats and drug-treated rats. The disruption of PPI was restored by administration of the antipsychotic drugs haloperidol (.2 mg/kg, IP) or clozapine (7.5 mg/kg, IP). CONCLUSIONS: The present results suggest that brain KYNA serves as an endogenous modulator of PPI and are consistent with the hypothesis that KYNA contributes to the pathophysiology of schizophrenia.     

Fertility in schizophrenia: results from a contemporary US cohort

To investigate procreation in schizophrenia, as well as gender-related differences, female patients with schizophrenia (n= 79, DSM-III-R criteria) were compared with screened female controls (n= 124) and subsequently with male patients (n=86). Two outcomes were investigated: (i) the proportion of subjects with one or more children (an index of fertility) and (ii) the number of children per subject among those with one or more children (an index of fecundity). Multivariate analysis was used to control for confounding variables. No significant differences in fertility between female patients and controls were detected, but reduced fecundity was noted among female patients past the reproductive period. Male patients showed a significant reduction in both fertility and fecundity compared to female patients. These results suggest that there is a relatively small impairment of fecundity among female patients compared with controls, but that there are more significant gender-related differences in both fertility and fecundity. The latter have important implications for the genetics of schizophrenia.     

Neurochemical Findings in the Cerebrospinal Fluid of Schizophrenic Patients with Tardive Dyskinesia and Neuroleptic-Induced Parkinsonism

Abstract: Monoamine and their acid metabolites were determined in the CSF of 18 drug-treated chronic schizophrenic patients with the symptoms of tardive dyskinesia and neuroleptic-induced Parkinsonism (Parkinsonism). Six healthy volunteers were used as the control group.
The norepinephrine (NE) levels were found to be significantly higher in the patients with tardive dyskinesia than in the controls. Furthermore, elevated CSF NE levels were also observed in the patients with Parkinsonism. Epinephrine (E) and Dopamine (DA) were not present in the CSF of the control group, whereas measurable levels of DA could be detected in 4 out of 9 and E was found in 8 out of 9 patients with tardive dyskinesia. The mean concentration of HVA was slightly but not significantly elevated in the patients with tardive dyskinesia and Parkinsonism. The mean values of CSF 5-HIAA were all within the normal range in both patient groups. From the above results, it was suggested that abnormal adrenergic activity rather than abnormal dopaminergic activity may play an important role as a mechanism in the etiopathogenesis of extrapyramidal disorders. Furthermore, in the patients with Parkinsonism, CSF neurochemical observations were similar to those of the patients with tardive dyskinesia in this study. It may help to explain the clinical coexistence of tardive dyskinesia and neuroleptic-induced Parkinsonism.     

Inositol 6 g daily may be effective in depression but not in schizophrenia

Inositol is an important precursor for second messenger synthesis and has been reported to be reduced by lithium treatment in rat brain and in human CSF in depression. An open trial of 6 g/day in 11 depressed patients resistant to previous treatment led to major improvement in nine patients. The enzyme synthesizing inositol has been reported to be elevated in schizophrenia, suggesting an attempted compensation for possible inositol deficiency. A controlled double-blind crossover trial in 10 chronic schizophrenic patients of 6 g/day of inositol for 30 days did not reveal any benefit.     

Sex difference in age at onset of schizophrenia: discrepant findings from India

Consecutive male (n=100) and female (n= 100) DSM-IV schizophrenics newly registered for treatment in a large psychiatric hospital were examined with regard to age at onset of the first psychotic symptom. Age at onset of the first psychotic symptom did not differ between the sexes regardless of whether schizophrenia was diagnosed by DSM-IV or by several alternative systems. Age at onset defined by other criteria, namely age at first contact with a physician, and age at first admission for psychiatric care, also did not show any differences between the sexes. Survival analysis of subjects having a documented date of birth revealed a female preponderance at younger ages. A higher positive symptom score predicted older age at onset of the first psychotic symptom in the total sample. These findings call into question the universality of the traditional view of a younger age at onset of schizophrenia among males. Tentative neurodevelopmental and cultural explanations are presented to explain why there is no sex difference in age at onset of schizophrenia in India.     

舒血宁治疗脑衰弱综合征的双盲对照研究

１４３例脑衰弱综合征患者随机分成舒血宁组和对照组，进行双盲的前瞻性研究。通过脑衰弱量表，打洞试验，连线实验的回查，结果表明：应用舒血宁治疗脑衰弱综合征，整体疗效明显优于对照组，脑衰弱量表的总评分显著优于对照组，而且对脑衰弱量表各个症状都有显著改善，易激惹，烦恼两项症状降分幅度较大，打洞、连线试验表明舒血宁治疗后患者的注意力、记忆力都有明显的改善，而且没有发现明显副作用。作者认为舒血宁治疗脑衰弱综合征有显著的作用，作为一种治疗脑血管疾患伴发精神症状和早期预防脑血管痴呆的新药是可行的。     

住院精神分裂症患者自杀危险因素调查

对全国９省市９所医院１０年间住院精神分裂症自杀死亡资料分析，自杀率占住院病人总数的０．６３％，占精神分裂症总数的０．７８％，占慢性精神分裂症的０，５０％。偏执型占６５．６·％。自杀原因受幻觉妄想支配２３．８％，悲观厌世２８．６％；精神症状好转（５９．５％）和自知力恢复期（４７．６％）易自杀。自杀方式自缢（５７．１％）和服药（２３．８％）居首。男性自杀多于女性。     

Human slow-wave sleep and the cerebral cortex

SUMMARY  Recent hypotheses about the roles of human slow-wave sleep (hSWS—delta EEG activity) are appraised. The possible linkage between hSWS and the functions of the prefrontal cortex (PFC) are explored with respect to normal subjects and to disorders involving PFC deficits.