Masahiro Asai

Elevated plasma nitrate levels in depressive states

BACKGROUND Previous 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. METHODS Plasma 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). RESULTS Plasma nitrate concentrations were significantly higher in depressed patients than in patients with an anxiety disorder (P<0.05) or in controls (P<0.01). LIMITATIONS The study group was small. The source of the surplus production of NO in patients with major depressive episode remains unclear. CONCLUSIONS These results suggest that NO production is increased in depression.

Association between dopamine D4 receptor (D4DR) Exon III polymorphism and novelty seeking in Japanese subjects

This study was designed to assess the association between novelty seeking and D4DR gene polymorphism in the Japanese population. The 48 bp repeat polymorphism in the third exon of the dopamine D4 receptor gene of 153 normal female students was correlated with personality feature results from the Japanese version of Cloningers Temperament and Character Inventory. The Novelty Seeking subscale of Exploratory Excitability had a significant association with long alleles of the polymorphic exon III repeat sequence of D4DR. Our results suggest that there is an association between long alleles of the polymorphic exon III repeat sequence of D4DR and the personality traits of the Novelty Seeking subscale of Exploratory Excitability, regardless of racial differences in the frequencies of D4DR exon III repeat polymorphism.

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.

Role of interleukin-1 in stress responses. A putative neurotransmitter.

Recently, the central roles of interleukin-1 (IL-1) in physical stress responses have been attracting attention. Stress responses have been characterized as central neurohormonal changes, as well as behavioral and physiological changes. Administration of IL-1 has been shown to induce effects comparable to stress-induced changes. IL-1 acts on the brain, especially the hypothalamus, to enhance release of monoamines, such as norepinephrine, dopamine, and serotonin, as well as secretion of corticotropin-releasing hormone (CRH). IL-1-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis in vivo depends on secretion of CRH, an intact pituitary, and the ventral noradrenergic bundle that innervates the CRH-containing neurons in the paraventricular nucleus of the hypothalamus. Recent studies have shown that IL-1 is present within neurons in the brain, suggesting that IL-1 functions in neuronal transmission. We showed that IL-1 in the brain is involved in the stress response, and that stress-induced activation of monoamine release and the HPA axis were inhibited by IL-1 receptor antagonist (IL-1Ra) administration directly into the rat hypothalamus. IL-1Ra has been known to exert a blocking effect on IL-1 by competitively inhibiting the binding of IL-1 to IL-1 receptors. In the latter part of this review, we will attempt to describe the relationship between central nervous system diseases, including psychological disorders, and the functions of IL-1 as a putative neurotransmitter.

The genetic structure of Cloninger's seven-factor model of temperament and character in a Japanese sample

Theoretical assumptions regarding the genetic and environmental structure of personality proposed in Cloningers seven-factor model of temperament and character were verified in a Japanese sample by using the twin method. The Temperament and Character Inventory (TCI) was administered to 296 twin pairs ranging in age from 14 to 28 years old. Among four temperament dimensions (novelty seeking [NS], harm avoidance [HA], reward dependence [RD], and persistence [PS]), HA and PS showed significant additive genetic contributions and no shared environmental effect, supporting the original theoretical assumption. NS and RD could be explained by either genetic or shared environmental factors with nonshared environment. All three character dimensions (cooperativeness [CO], self-directedness [SD], and self-transcendence [ST]) could be explained exclusively by additive contributions and no shared environmental effect. Multivariate genetic analysis indicated that there were no significant associations between NS, HA, and RD, as the theory predicts, and the genetic components of PS, SD, and CO were derived from those of the temperament dimensions. The fourth genetic component, which had a substantial load specifically on ST and overlapped with PS, was identified. Although most of the nonshared environmental effects were trait-specific, the phenotypic correlation between NS and HA could be explained by nonshared environmental overlap.

Serum interleukin-18 levels are elevated in schizophrenia

Interleukin-18 (IL-18) is a recently discovered proinflammatory cytokine which plays a pivotal role in T helper 1 (Th1) responses. IL-18 is produced by macrophage-like cells, and inappropriate IL-18 production has been known to be involved in immunological disturbances. Schizophrenia is a common disease whose pathogenesis is still unclear; however, an activation of the inflammatory response system, including the Th1 cytokine response, may be related to the pathophysiology of schizophrenia. We measured the serum IL-18 levels of 66 schizophrenics and age- and sex-matched control subjects by using an ELISA assay. We found significantly increased serum IL-18 levels in the schizophrenic patients (P=0.0002). This finding supports the hypothesis that immune activation is involved in the pathophysiology of schizophrenia.

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.

Depression and ventricular enlargement.

ABSTRACT– Compared with controls, 46 depressed patients showed increased ventricular‐brain ratio (VER). Patients with poor outcome, single episode, onset at 50 years or over, or without melancholia were found to have greater VBR than controls.

Use of herbal medicine for treating psychiatric disorders in Japan

Alongside the Western pharmacotherapy that is now the major medical modality in Japan, we continue to offer a number of traditional remedies. We prefer to allow patients to choose between these two approaches, after explaining the advantages and potential adverse effects of each. Research into the traditional treatments continues, and we now have a number of studies available concerning the efficacy of oriental herbal medicine (Kampo medicine) in Japan. There are about 120 different prescriptions available for treatment. Herbs are believed to affect both the psyche and soma, and Kampo medicine does not differentiate between them. Improvement brought about by herbal medicine is usually mild and slow, but sometimes very drastic. Side effects are rare. Those that do occur are mostly allergic reactions to natural substances. Therefore, herbal medicine is especially useful for elderly patients and patients with physical complications. Prescription is traditionally selected by judging Sho of a patient. Sho is equivalent to a syndrome, but comprises psycho and somatic symptoms and signs obtained by traditional physical examination that focuses constitution, general physical condition, pulse, abdominal signs, and examination of the tang. However, currently modern diagnoses are also applied to deciding upon the prescription. Western physicians can select the appropriate preparation without having a special knowledge of Oriental medicine.

Impact of sociodemographic and diabetes‐related characteristics on depressive state among non‐insulin‐dependent diabetic patients

Abstract  One hundred and fifty‐one non‐insulin‐dependent diabetic patients were assessed to detect sociodemographic, psychological and disease‐related characteristics that were related to depressive state among diabetic patients. Depressive state in the patients was correlated with poor social support and low economic status, premorbid neurotic personality and the presence of complications, retinopathy in particular. However, depressive state did not correlate with age, gender, education, serum level of HbA1C or duration of diabetes. The severity of the depressive state in diabetic patients may vary with the cultural background of the patient and/or the country in which he or she is living. In treating diabetic patients, doctors need to pay special attention to these factors.