Jun Nakamura

Lithium and dementia: A preliminary study

Recent studies have shown that lithium may block the accumulation of amyloid-beta (Abeta) peptides and to inhibit the hyperphosphorylation of tau via the inhibition of GSK-3alpha in the brain of mice. The purpose of the present study is to examine whether lithium could potentially be effective for the prevention of Alzheimers disease. We investigated the clinical records of 1,423 outpatients at a university psychiatric outpatient clinic and classified patients according to the following criteria: (a) absence of a diagnosis of dementia, (b) age 60 years or older, and (c) lithium had been prescribed and/or was currently prescribed. We compared these patients with randomly selected age and gender matched control group who had never been prescribed lithium. Despite no significant difference in MMSE scores between the lithium group, which consisted of patients receiving lithium treatment, and the control group, those who had previously received lithium and/or were currently prescribed lithium had significantly better MMSE scores than the control patients. The findings provide partial evidence to support the contention that lithium could offer hope as a preventive treatment for Alzheimers disease. Further prospective studies with a large number of patients are warranted to investigate this potentially important effect.

Does plasma free-3-methoxy-4-hydroxyphenyl (ethylene) glycol increase in the delirious state? A comparison of the effects of mianserin and haloperidol on delirium

Sixty-six patients (47 men, 19 women, mean age 65 years) with delirium were treated with mianserin (10–60 mg/day) or haloperidol (2–6 mg/day) at Kurume University Hospital. The clinical effects of these drugs were compared before and after treatment using the Delirium Rating Scale. At the same time, blood was sampled to analyse plasma mianserin, free-3-methoxy-4-hydroxyphenyl (ethylene) glycol (MHPG) and homovanillic acid concentrations. Marked improvement after 1 week was observed in 69.4% of patients undergoing mianserin treatment, and in 70.6% of those receiving haloperidol. A statistically significant difference in the clinical effects of these drugs was not observed. Although improvement in the delirious state and a decrease in the plasma free-MHPG concentration were observed after drug administration, the plasma free-homovanillic acid concentration showed no significant change. The higher plasma free-MHPG concentration in the delirious state suggests the existence of a preparatory state whereby noradrenaline metabolism is involved in the appearance of the abnormal behaviour associated with delirium. These data suggest that free-MHPG concentrations could potentially be used as a predictor of delirium.

Circadian rhythms of hormone concentrations in alcohol withdrawal.

Abstract We investigated the circadian rhythm of hormones (Cortisol, melatonin) in alcoholic patients during and 1 month after alcohol withdrawal. Patients with delirium tremens had irregular serum hormone concentration rhythms during withdrawal, which normalized after the withdrawal period. Patients without delirium tremens had normal circadian rhythms even during the withdrawal period. We speculated that the disturbance of the biological oscillator, in terms of the decline of synchronizing function or the decrease in synchronizing factors, caused abnormal circadian rhythms of hormone release during delirium tremens.

Effects of caffeine on event-related potentials: Comparison of oddball with single-tone paradigms

We investigated the acute effects of caffeine (500 mg) on event‐related potentials (ERP) in 10 healthy subjects using standard oddball and single‐tone paradigms. Event‐related potentials were recorded before oral ingestion of caffeine or placebo and 30 min and 210 min after. The oddball paradigm, but not the single‐tone paradigm, showed that the P300 amplitude and the area were significantly increased 30 min after ingestion of caffeine and significantly decreased 30 min after ingestion of placebo. The effects of caffeine disappeared at 210 min. Neither the P300 latency nor the reaction time changed significantly with the oddball paradigm. However, the reaction time was shortened 30 min after ingestion of caffeine with the single‐tone paradigm. These findings suggest that the caffeine‐induced increase in the P300 amplitude may have resulted from the increased allocation of attentional resources to the discriminating process which was not, however, accompanied by facilitation of the process and that caffeine may specifically stimulate the discriminating process involved in the oddball paradigm. In addition, the simple psychomotor performance of button‐pressing in response to a tone signal was accelerated by caffeine.

Risperidone in the treatment of psychotic depression.

In the preset study, the authors investigated that effects of the antipsychotic drug risperidone on psychotic depression and examined the mechanism of risperidone to ameliorate psychotic depression. Fifteen patients met the DSM-IV criteria for major depressive disorder with psychotic features and the remaining five patients met those for bipolar I disorder (most recent episode depressed) with psychotic features (M/F: 8/12, age: 54+/-18). All patients were evaluated regarding their clinical improvement using the Hamilton Rating Scale for Depression (Ham-D), and Positive and Negative Syndrome Scale (PANSS). In addition, plasma concentrations of HVA and MHPG were analyzed by HPLC. Patients with a 50% or more improvement in Ham-D score were defined as responders. Three were prescribed risperidone alone, and the other 17 were administered risperidone as an addition to preexisting antidepressants or mood stabilizers. The preexisting antidepressants or mood stabilizers were as follows: paroxetine (6), lithium (3), valproic acid (3), clomipramine (2), fluvoxamine (1), amitriptyline (1), amoxapine (1). The average dose of risperidone was 1.8+/-0.5 mg/day. Eleven of twenty patients (55%) turned out to be responders 4 weeks after initiation of risperidone administration. No differences were observed between responders and nonresponders with respect to age, sex, Ham-D score before risperidone treatment, dose and plasma level of risperidone or its active metabolite, 9-hydroxyrisperidone. Plasma HVA levels before risperidone administration in responders were significantly higher than those in nonresponders. In addition, a significant correlation was observed between changes in plasma HVA level and the percentage improvement on Ham-D score. These results indicate that treatment with risperidone is effective to ameliorate psychotic depression, and the influence of risperidone on dopaminergic activity is associated with its efficacy.

Smoking motivation in normal subjects using event-related potentials

The goal of the present study was to evaluate the effects of acute nicotine administration following 18 h of abstinence from cigarette smoking. Event‐related potentials (ERPs) were measured in 13 male volunteers for five successive sessions. The peak amplitude and the area of the P300 significantly increased during acute withdrawal. An increase in P300 values also was observed following resumption of smoking. However, in subjects pretreated with nicotine gum, no increase in P300 values was observed following resumption of smoking. The increase in P300 values persisted for several weeks and returned to control values following 1 month of routine daily smoking. The P300 amplitude was negatively correlated with the daily dose of nicotine. These results suggest that attention and/or arousal may be enhanced by the withdrawal and the resumption of smoking. The mechanisms involved in CNS hypersensitivity to motivate the subject to smoke may persist in the presence of an increased P300 value, even following resumption of routine daily smoking.

Frontal midline theta activity and platelet MAO in human subjects

The distinctive theta rhythm that appears at the frontal midline during the performance of mental tasks has been designated as frontal midline theta (Fm theta). Fm theta shows individual differences and seems to be related to certain personality traits. In several studies, it has been indicated that low platelet monoamine oxidase (MAO) activity is also associated with certain personality traits. In the present study, we found a negative correlation between the appearance of Fm theta and platelet MAO activity. Subjects with marked extroversion show a high amount of Fm theta and low MAO activity. It is therefore suggested that Fm theta, an electrophysiological marker, may be useful in the investigation of monoamine functions in the central nervous system (CNS) by way of platelet MAO activity, a biochemical marker.

Platelet monoamine oxidase activity and personality traits in alcoholics and methamphetamine dependents

Personality traits of alcoholics and methamphetamine dependents were examined by Karolinska scales of personality (KSP). The two groups differed with respect to Aggression, but, they were basically same in Impulsiveness. The biological marker platelet monoamine oxidase (MAO) activity showed a significant difference between the two groups. The low platelet MAO activity in alcoholics may suggest a certain biological basis to be involved in the etiology of dependence whereas the higher platelet MAO activity observed in methamphetamine dependents may reflect the prolonged use of methamphetamine and/or treatment with neuroleptics, or some biological basis.

No association between a functional NAD(P)H

Several lines of evidence have indicated that free radicals may play a role in the pathophysiology of tardive dyskinesia (TD) (reviewed in Andreassen and Jorgensen, 2000). NAD(P)H: quinone oxidoreductase (NQO1) is an important enzyme in the human body that counteracts the oxidative stress-induced neuronal injury caused by the toxic free radicals such as dopamine-semiquinones. Taking the possible genetic predisposition to TD into account (Yassa and Ananth, 1981), the NQO1 gene is a good candidate gene that may confer increased susceptibility to TD. Based on this hypothesis, Pae et al. (2004) reported a significant association between the Pro187Ser polymorphism in the NQO1 gene and TD. In the present study, we attempted to replicate the findings of Pae et al. (2004) with the same polymorphism in 222 Japanese patients with schizophrenia. No significant difference was detected between patients with and without TD in the allelic distribution (χ2=0.070, d.f.=1,p=0.795) and in the genotypic distribution (χ2=0.910,d.f.=2,p=0.657). In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the three genotype groups (p=0.49). Our results suggest that the NQO1 gene polymorphism does not confer an increased risk of TD.

Reliability of the task‐related component (P3b) of P3 event‐related potentials

Abstract Within session and between session reliabilities of the task‐related component (P3b) of the P3 measures (amplitude, area and latency) and their habituation across eight sessions separated by 7–10 days, except for an interval of 1 month between the 6th and 7th sessions, were studied based on the difference waves, which were obtained by subtracting the ignored infrequent event‐related potentials (ERP) from the target ERP elicited by a standard auditory oddball paradigm with eyes‐open or eyes‐closed conditions in 10 normal subjects. The within session reliabilities represented as Pearson correlation coefficients (r) were 0.57‐0.66 for the three measures except for those for the latency and amplitude under the eyes‐closed condition. The between session reliabilities expressed as intraclass correlation coefficients (R) ranged from 0.54 to 0.60 except for that for latency under eyes‐closed conditions. Long‐term habituation occurred within the first six sessions for the P3b amplitude and area, and dishabituation took place in the 7th session after an interval of 1 month, whereas no such phenomenon was observed for the P3b latency. Implications of the present results are discussed in terms of the clinical application of the P3 measures.