Naohisa Uchimura

Hyperpolarizing and depolarizing actions of dopamine via D-1 and D-2 receptors on nucleus accumbens neurons

The effect of dopamine (DA) on the nucleus accumbens neurons in guinea-pig brain slices was studied by intracellular recordings. DA caused a hyperpolarization in 28% of the neurons tested, a depolarization in 11%, and a hyperpolarization followed by a depolarization in 53%. The remaining neurons were unaffected. Analyses of the responses revealed that the DA hyperpolarization was produced by activation of the D-1 receptor and associated with an increase in potassium conductance, whereas the DA depolarization was generated by activation of the D-2 receptor and accompanied by a decrease in potassium conductance. DA uptake inhibitors augmented both the hyperpolarizing and depolarizing responses, while cyclic adenosine monophosphate selectively enhanced the former.

Melatonin therapy for REM sleep behavior disorder

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia with clinical symptoms that include punching, kicking, yelling and leaping out of bed in sleep. Polysomnographic (PSG) finding showed REM sleep without muscle atonia. Clonazepam is generally used for treating RBD symptoms but melatonin was reported to be effective so we reconfirmed the effect of melatonin on RBD patients in the present study. We used melatonin (3–9 mg/day) which could ameliorate problem sleep behaviors remarkably, as well as %tonic activity in PSG variables. In the present study, melatonin was reconfirmed to be effective in RBD symptoms, especially for patients with low melatonin secretion, while its mechanism was not clearly known in the present study.

Sleep Findings in Young Adult Patients with Posttraumatic Stress Disorder

BACKGROUND Laboratory sleep studies in posttraumatic stress disorder (PTSD) have not provided consistent evidence of sleep disturbance, despite apparent sleep complaints. Most of these studies have investigated middle-aged chronic PTSD subjects with a high prevalence of comorbidities such as substance dependence and/or personality disorder. METHODS Ten young adult PTSD patients (aged 23.4 +/- 6.1 years) without comorbidities of substance dependence and/or personality disorder underwent 2-night polysomnographic recordings. These sleep measures were compared with those of normal control subjects and were correlated with PTSD symptoms. RESULTS Posttraumatic stress disorder patients demonstrated significantly poorer sleep, reduced sleep efficiency caused by increased wake time after sleep onset, and increased awakening from rapid eye movement (REM) sleep (REM interruption). We found significant positive correlations between the severity of trauma-related nightmare complaints and the percentage of REM interruption, as well as wake time after sleep onset. CONCLUSIONS The results indicate that trauma-related nightmares are an important factor resulting in increased REM interruptions and wake time after sleep onset in PTSD.

Study of image findings in rapid eye movement sleep behavioural disorder

Abstract To elucidate the cause of idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), magnetic resonance imaging and single‐photon emission computed tomography of the brain were conducted on 20 patients with RBD. Blood flow in the upper portion of both sides of the frontal lobe and pons was significantly lower in patients with RBD than in the normal elderly group. Among the patients with RBD, decreased blood flow in the frontal lobe showed no correlation with the extent of frontal lobe atrophy. Decreased blood flow in the upper portion of the frontal lobe and pons might be associated with the pathogenesis of idiopathic RBD.

GABRB2 Association with Schizophrenia: Commonalities and Differences Between Ethnic Groups and Clinical Subtypes

BACKGROUND Single nucleotide polymorphisms (SNPs) and haplotypes in intron 8 of type A gamma-aminobutyric acid (GABA(A)) receptor beta2 subunit gene (GABRB2) were initially found to be associated with schizophrenia in Chinese. This finding was subjected to cross-validation in this study with Japanese (JP) and German Caucasian (GE) subjects. METHODS Single nucleotide polymorphisms discovery and genotyping were carried out through resequencing of a 1839 base pair (bp) region in GABRB2. Tagging SNPs (tSNPs) were selected based on linkage disequilibrium (LD), combinations of which were analyzed with Bonferroni correction and permutation for disease association. Random resampling was applied to generate size- and gender-balanced cases and control subjects. RESULTS Out of the 17 SNPs (9.2/kilobase [kb]) revealed, 6 were population-specific. Population variations in LD were observable, and at least two low LD points were identified in both populations. Although disease association at single SNP level was only shown in GE, strong association was demonstrated in both JP (p = .0002 - .0191) and GE (p = .0033 - .0410) subjects, centering on haplotypes containing rs1816072 and rs1816071. Among different clinical subtypes, the most significant association was exhibited by systematic schizophrenia. CONCLUSIONS Cross-population validation of GABRB2 association with schizophrenia has been obtained with JP and GE subjects, with the genotype-disease correlations being strongest in systematic schizophrenia, the most severe subtype of the disease.

Stigma associated with schizophrenia: Cultural comparison of social distance in Japan and China

Aims:  The aim of the present study was to investigate social attitudes toward schizophrenia in Japan and China in view of social distance and knowledge of psychiatry, as well as sociocultural aspects.

Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: Contribution of daytime sleepiness to residual depressive symptoms

BACKGROUND Although extensive studies have indicated a relationship between obstructive sleep apnea (OSA) and depressive symptoms, the effect of continuous positive airway pressure (CPAP) treatment on residual depressive symptoms in patients with both major depressive disorder (MDD) and coexisting OSA has not been examined. METHODS Seventeen patients with continued MDD despite pharmacotherapy such as antidepressants and/or benzodiazepines, who also had comorbid OSA, were required to complete the Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HRSD), and Epworth sleepiness scale (ESS) at the commencement of the study and then again after 2 months of CPAP treatment. RESULTS BDI and HRSD scores decreased from 19.7 to 10.8 and 16.7 to 8.0 after 2 months of CPAP treatment (both p<0.01). We also found significant correlations among the improvement rates in BDI, HRSD and ESS scores (R=0.86 and 0.75, both p<0.01). The mixed effect model demonstrated a significant ESS effect on BDI and HRSD. CONCLUSIONS The results suggest that MDD patients with residual depressive symptoms despite pharmacotherapy who also have symptoms of suspected OSA, such as loud snoring, obesity, and daytime sleepiness, should be evaluated for sleep apnea by polysomnography and treated with an appropriate treatment such as CPAP. CPAP treatment may result in a significant improvement of residual depressive symptoms due to the improvement of daytime sleepiness in these patients.

Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study.

Attention to risk of antipsychotics for older patients with delirium has been paid. A clinical question was whether risk of antipsychotics for older patients with delirium would exceed efficacy of those even in the general hospital setting.

Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis

D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, -141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and -521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p=0.04, odds ratio (OR)=0.42, 95% CI; 0.27-0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p=0.014, OR=0.34, 95% CI; 0.22-0.54). The genotype of -141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p=0.00037, OR=3.62, 95% CI 2.48-5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.

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.