Eiji Suzuki

Elevated plasma nitrate levels in depressive states

BACKGROUNDnPrevious studies have shown that nitric oxide (NO) synthase inhibitors show preclinical antidepressant-like properties, suggesting that NO is involved in the pathogenesis of depression. The purpose of this study is to examine whether or not NO production increases in depressed patients.nnnMETHODSnPlasma nitrate concentrations, an index of NO production, were measured by high-performance liquid chromatography in depressed patients (n=17) and compared with patients suffering anxiety (n=6) and with healthy controls (n=12).nnnRESULTSnPlasma nitrate concentrations were significantly higher in depressed patients than in patients with an anxiety disorder (P<0.05) or in controls (P<0.01).nnnLIMITATIONSnThe study group was small. The source of the surplus production of NO in patients with major depressive episode remains unclear.nnnCONCLUSIONSnThese results suggest that NO production is increased in depression.

Serum interleukin-6 in schizophrenic patients

We examined serum interleukin-6 (IL-6) in 90 schizophrenic patients in remission and 90 normal controls using enzyme-linked immuno-sorbent assay (ELISA). We found a significant difference in variation between the schizophrenic and the control groups (F = 10.9, P less than .002). The difference in distribution was also statistically significant by Kolmogorov-Smirnov (chi-square = 45.0, P less than .001). Eight patients had aberrantly high serum levels of interleukin-6. Since the higher levels of IL-6 are characteristically found in several autoimmune disorders, our finding suggests a link between schizophrenia and immune response, which could be either autoimmune or a process induced by reactivation of viruses.

Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders

Disturbances in dopaminergic systems have been implicated in the etiology of mood disorders. Although genetic factors also play an important role, no major gene has been identified. We conducted an association study using the dopamine D2, D3 and D4 receptor, and transporter gene polymorphisms, comparing 101 mood-disorder patients (52 bipolar and 49 unipolar) and 100 controls. Our results suggest that there is a significant association between the dopamine D4 receptor gene and mood disorders, especially major depression, but no association between the other polymorphisms and mood disorders. Further investigations are needed to clarify the clinical significance of this association in the pathophysiology of mood disorders.

Induction of interleukin-1β and interleukin-1 receptor antagonist mRNA by chronic treatment with various psychotropics in widespread area of rat brain

We investigated whether psychotropics orally administered to rats affect levels of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra) mRNA in the hypothalamus, hippocampus, frontal cortex, and brain stem, using a reverse transcription-polymerase chain reaction method. The psychotropics tested were chlorpromazine, haloperidol, imipramine, maprotiline, fluvoxamine, and diazepam. Treatment for 28 days raised the levels of both mRNAs. The increase in IL-1Ra mRNA was 6-112 times larger than that of IL-1 beta mRNA in most brain regions examined. These results suggest that chronic treatment with psychotropics causes greater amplifying effects on IL-1Ra mRNA than IL-1 beta mRNA in the brain.

Immobilization Stress Increases mRNA Levels of Interleukin-1 Receptor Antagonist in Various Rat Brain Regions

Abstract1. Interleukin-1 receptor antagonist (IL-1Ra), as well as the interleukin-1β (IL-1β) gene response to immobilization stress (IMS), was examined in the rat brain. The reverse transcription–polymerase chain reaction was employed to determine mRNA levels.2. IL-1β and IL-1Ra mRNA levels peaked at approximately 0.5 and 2–4 hr, respectively. The maximum mRNA levels of IL-1β were 15-fold higher than pre-IMS levels, whereas those of IL-1Ra were 250-fold higher in the hypothalamus.3. After the biosynthesis of IL-1β has peaked, IL-1Ra may contribute to attenuation of the IL-1 activity which has been enhanced by IMS.

Monoamine oxidase genes polymorphisms and mood disorder

We investigated a genetic association between mood disorders (bipolar and unipolar) and the alleles of monoamine oxidase (MAO) A and B (MAOA and MAOB). One hundred and twelve unrelated Japanese patients (60 bipolar, 52 unipolar) and 100 controls were genotyped for three markers of MAOA and for one marker of MAOB. No statistically significant difference in the distribution of the alleles existed between cases and controls. Therefore, our results did not support the involvement of the alleles at MAOA and MAOB in the etiology of mood disorder.

Schizophrenic patients with deficit syndrome have higher plasma homovanillic acid concentrations and ventricular enlargement

In order to investigate the biological characteristics of deficit syndrome in schizophrenia (Carpenter et al 1988), we examined cerebroventricular ratios (CVRs) and plasma concentrations of homovanillic acid (HVA) in a group of schizophrenic inpatients with deficit syndrome (n = 20) and in a control group of age- and sex-matched schizophrenic inpatients without deficit syndrome (n = 20). Symptoms and intelligence levels were measured using the Brief Psychiatric Rating Scale (BPRS) and the Wechsler Adult Intelligence Scale (WAIS), respectively. Patients in the deficit group had significantly higher CVRs as well as significantly elevated plasma HVA concentrations when compared with patients in the nondeficit group. We also found that the mean total WAIS score in the deficit group was significantly lower than that in the nondeficit group. These findings suggest the biological heterogeneity of schizophrenia. Increased central dopaminergic turnover, as indicated by higher plasma HVA concentrations, may partially account for the pathogenesis of deficit syndrome.

Longitudinal changes in symptoms and plasma homovanillic acid levels in chronically medicated schizophrenic patients

A correlation has been noted between the changes in plasma homovanillic acid concentrations and changes in psychiatric symptoms induced by neuroleptic treatment. Our objective was to determine whether plasma homovanillic acid concentration changed in accordance with the changes in symptoms over time. Twenty-eight chronically medicated schizophrenic inpatients received the same treatment regimen for 1 year. Symptoms and plasma homovanillic acid concentrations were examined every month and whenever conditions deteriorated. Plasma homovanillic acid concentrations were significantly higher in the patients in the worst condition than in the patients in the best condition. Further, when comparing the best and worst conditions of both the positive and negative symptoms, the change in psychiatric rating of positive and negative symptoms was correlated significantly with the change in plasma homovanillic acid level. These results suggest that a change in plasma homovanillic acid concentration can be produced not only by neuroleptic-induced dopaminergic blocking but also by a change in positive and negative symptoms of schizophrenia.

Plasma homovanillic acid, plasma anti-D1 and -D2 dopamine-receptor activity, and negative symptoms in chronically medicated schizophrenia

We have investigated the relationship between the concentration of homovanillic acid in human plasma (pHVA) and plasma anti-D1 and anti-D2 dopamine receptor activity in chronic schizophrenic patients whose neuroleptic dosage was changed. The change in pHVA level correlated with that in anti-D1, not anti-D2 activity, thus suggesting that the neuroleptic-induced changes in pHVA concentration may be associated with the blocking of D1- as well as D2- receptors. The change of scores on the Scale for the Assessment of Negative Symptoms did not significantly correlate with changes in anti-D1 or anti-D2 activity, but did so correlated with the change in pHVA level.

Endothelium-independent and -dependent vasoactivity of 6-nitronorepinephrine

Vasoactivities of 6-nitronorepinephrine were investigated using rat aorta. 6-Nitronorepinephrine (> 100 microM) caused dose-dependent contraction in both endothelium-intact and -denuded aorta, although the latter showed greater contraction than the former. Prazosin (> 3 nM), an alpha1-adrenoceptor antagonist, attenuated significantly the 6-nitronorepinephrine-induced contractions, thereby suggesting the alpha1-adrenoceptor involvement. Aortic rings prepared from reserpine-pretreated rats showed the 6-nitronorepinephrine-induced a contraction to the extent similar to those from untreated rats, suggesting that endogenous norepinephrine does not play a role in the 6-nitronorepinephrine-induced contraction. 6-Nitronorepinephrine (> 10 microM) potentiated norepinephrine-induced contraction only in the presence of endothelium. The augmentation was attenuated by catalase (1200 U/ml). H2O2 (10-300 microM) augmented the norepinephrine-induced contraction only in the endothelium-intact rat aortic rings. 6-Nitronorepinephrine attenuated significantly acetylcholine-induced relaxation. Catalase prevented the 6-nitronorepinephrine-induced inhibition of the acetylcholine-induced relaxation. These results suggest that 6-nitronorepinephrine has a weak alpha1-adrenoceptor agonistic property and that the endothelium-dependent potentiation by 6-nitronorepinephrine of the norepinephrine-induced contraction is mediated through production of H2O2.