Search

Hiroyuki Karibe,1 Michihiko Koeda,2 Kyoko Aoyagi-Naka,1 Yuichi Kato,1 Amane Tateno,2 Hidenori Suzuki,3 Yoshiro Okubo21Department of Pediatric Dentistry, School of Life Dentistry at Tokyo, Nippon Dental University, Tokyo, Japan; 2Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; 3Department of Pharmacology, Nippon Medical School, Tokyo, JapanPurpose: The sound of dental treatments can evoke anxiety in some dental patients. While women have shown greater dental anxiety than men, little is known about the gender differences in the perception of dental sounds. The purpose of this preliminary study was to evaluate differences in the perception of dental sounds according to the level of dental fear and gender.Patients and methods: Based on the level of dental fear, 69 adults (39 women, 30 men; average age, 28.1±8.1 years) were categorized into four groups. Three types of sounds were presented to participants: two sounds associated with dental treatment and a neutral sound. All participants rated their emotional reaction to each sound on a visual analog scale.Results: Significant differences were observed for ratings of valence and disgust for a dental drilling sound among the four groups (p=0.007 and 0.004, respectively). Female participants in the dental fear group rated the dental drilling sound as more negative and disgusting than did female participants in the control group (p=0.002 for both ratings). However, no significant differences were found in ratings between males in the dental fear and control groups.Conclusion: Perception of dental sounds appears to differ by level of dental fear and by gender. Considering these differences may contribute to reducing fear in dental patients.Keywords: dental anxiety, adult, auditory stimuli, sound, visual analog scale

Atsuko Kawai,1,2 Masatake Kurita,1,3,4 Satoshi Nishino,3,4 Eishin Hirata,5 Tadahiro Sato,5 Yoshiro Okubo1 1Department of Psychiatry and Behavioral Science, Nippon Medical School, Bunkyo-ku, 2Total Health Clinic, Nanyo, 3Natori Station Front Clinic, Natori, 4Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 5Sato Hospital, Nanyo, Japan Abstract: Many smokers find it difficult to stop smoking without assistance. The antidepressants bupropion and nortriptyline can aid smoking cessation. The main aim of this study was to understand the pathophysiology of smoking cessation better based on biological backgrounds. We investigated the following biological markers for any alterations during smoking cessation in the absence of pharmacotherapy: the dopamine metabolite homovanillic acid (HVA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and brain-derived neurotrophic factor (BDNF). Assessment and blood sampling were performed at a baseline (the start) time point and at a critical time point during smoking cessation. Seven of 30 smokers quit during a 16-week follow-up period; these smokers were defined as remission group from tobacco dependence. The remaining 23 smokers were categorized as hardcore smokers. The smoking group was compared with 23 non-smokers matched for age and gender. We compared blood levels of biological markers in each of the three groups. The hardcore smoker group showed significant decreases in HVA and MHPG levels between baseline and the critical time point (p=0.018 and p=0.033, respectively). However, the remission from tobacco dependence group exhibited no significant changes in any of the biomarkers examined. They had lower scores on the Minnesota nicotine withdrawal scale than the hardcore smoker group (p=0.002). The hardcore smoker group had higher MHPG and BDNF levels than the non-smoker group (p=0.002 and p

Masatake Kurita,1–3 Takahiro Moriya,2 Satoshi Nishino,2,4 Eishin Hirata,4 Noriyasu Hirasawa,5 Yoshiro Okubo,3 Tadahiro Sato4 1Wakamiya Hospital, Koutokukai, Yoshihara, Yamagata, 2Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 3Department of Psychiatry and Behavioral Science, Graduate School of Medicine, Nippon Medical School, Sendagi, Tokyo, 4Sato Hospital, Koutokukai, Kunugizuka, Nanyo, Yamagata, 5Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan Abstract: A woman was diagnosed with non-24-hour sleep–wake syndrome and depressive symptoms. Her depressive symptoms did not respond to standard doses of several antidepressants or mood stabilizers. Furthermore, her sleep–wake cycle remained non-entrained despite treatment with a melatonin-related drug, vitamin B12, and phototherapy. Ultimately, her sleep–wake rhythm was restored to a 24-hour pattern with a low dose of valproic acid, and her depressive symptoms tended to improve as a result of synchronization without antidepressants. Low-dose valproic acid appears to be one of the effective means of entraining circadian rhythms in patients with non-24-hour sleep–wake syndrome, which in turn likely improves associated depressive symptoms. Keywords: circadian rhythm sleep disorder, mood stabilizers, vitamin B12, melatonin, phototherapy, antidepressants, depression

Kenji Takeyoshi,1,2 Masatake Kurita,1–3 Satoshi Nishino,2,3 Mika Teranishi,1 Yukio Numata,2 Tadahiro Sato,2 Yoshiro Okubo11Department of Psychiatry and Behavioral Science, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, 2Sato Hospital, Koutokukai, Nanyo, Yamagata, 3Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, JapanAbstract: Although three drugs, risperidone, yokukansan, and fluvoxamine, have shown equal efficacy in treating behavioral and psychological symptoms of dementia (BPSD) in our previous study, their mechanisms of action are different from one another. Monoamines have attracted attention for their key roles in mediating several behavioral symptoms or psychological symptoms through synaptic signaling. We aimed to clarify the monoamines changed by treatment with each drug in patients with BPSD. The main purpose of this study was to determine whether plasma levels of catecholamine metabolites are correlated with pharmacological treatments. This was an 8-week, rater-blinded, randomized, flexible-dose, triple-group trial. In total, 90 subjects were recruited and subsequently three different drugs were allocated to 82 inpatients with BPSD. We examined BPSD data from patients who completed 8 weeks of treatment. Eventually, we analyzed 42 patients (yokukansan: 17; risperidone: 9; fluvoxamine: 16). Homovanillic acid, a metabolite of dopamine, and 3-methoxy-4-hydroxyphenylglycol, a metabolite of noradrenaline, in their plasma were analyzed by high-performance liquid chromatography with electrochemical detection. All three drugs showed equal significant efficacy between baseline and study endpoint. By contrast, biomarkers showed mutually different changes. Patients in the yokukansan group had significantly decreased plasma homovanillic acid levels from baseline. Conversely, patients in the risperidone and fluvoxamine groups exhibited no significant changes in plasma homovanillic acid levels from baseline. Yokukansan contains geissoschizine methyl ether, which is known to have a partial agonist effect on dopamine D2 receptors. An improvement in BPSD condition with the intake of yokukansan is suggested to occur through a suppressed dopaminergic function, which is similar to the effect of aripiprazole.Keywords: herbal medicine, MHPG, homovanillic acid, HVA, noradrenaline, BPSD

Satoshi Ueda,1 Takeshi Sakayori,1 Ataru Omori,2 Hajime Fukuta,3 Takashi Kobayashi,3 Kousuke Ishizaka,1 Tomoyuki Saijo,4 Yoshiro Okubo1 1Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; 2Tamachuo Hospital, Tokyo, Japan; 3Kurumegaoka Hospital, Tokyo, Japan; 4Saijo Clinic, Tokyo, Japan Abstract: Neuroleptics can induce not only physical adverse effects but also mental effects that produce deficit status in thought, affect, cognition, and behavior. This condition is known as neuroleptic-induced deficit syndrome (NIDS), which includes apathy, lack of initiative, anhedonia, indifference, blunted affect, and reduced insight into disease. Although this old concept now appears almost forgotten, neuroleptics, whether typical or atypical, can make depression or bipolar disorder resemble other more refractory conditions, readily leading to mistaken diagnosis and inappropriate treatment. The authors describe three cases of NIDS superimposed on depressive phase in bipolar disorder with psychosis, where the attending psychiatrist’s failure to recognize NIDS prevented patients from receiving effective treatment and achieving remission. All cases achieved remission after reduction of neuroleptics and intensive therapy, including electroconvulsive therapy, for bipolar depression. The concept of NIDS was originally introduced for schizophrenia, and it has rarely been highlighted in other diseases. In recent years, however, atypical antipsychotics are being more often administered to patients with bipolar disorder. Psychiatrists, therefore, should also remember and exercise caution regarding NIDS in the pharmacotherapy of bipolar disorder with and without psychosis. The authors believe that the concept of NIDS needs to be reappraised in current psychiatry. Keywords: neuroleptic-induced deficit syndrome (NIDS), bipolar disorder, psychosis, atypical antipsychotics, electroconvulsive therapy

Masatake Kurita,1–3 Satoshi Nishino,1,2 Yukio Numata,1 Yoshiro Okubo,3 Tadahiro Sato11Sato Hospital, Koutokukai, Nanyo, Yamagata, Japan; 2Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan; 3Department of Psychiatry and Behavioral Science, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, JapanBackground: Treatment of the depressive and manic states in bipolar disorder I (BDI) is a challenge for psychiatrists. Despite the recognized importance of the switch phenomenon, the precise mechanisms underlying this process are yet to be shown. We conducted a naturalistic study in two BDI patients to determine whether biological markers (monoamine metabolites and brain-derived neurotrophic factor [BDNF]) are associated with the switch between depressive and manic states.Case presentation and methods: Blood sampling and mood assessments were performed at 2-week intervals over a period of 2 (Case 1, n=72) and 6 (Case 2, n=183) years. Plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography with electrochemical detection. Plasma BDNF was assayed by sandwich ELISA (enzyme-linked immunosorbent assay).Results: MHPG had the highest standardized coefficient (β) in the multiple regression analysis. We found a significant positive correlation between Young Mania Rating Scale scores and plasma MHPG levels (Case 1: р=0.429; Case 2: р=0.488), and a significant negative correlation between Montgomery–Asberg Depression Rating Scale scores and MHPG levels (Case 1: р=-0.542; Case 2: р=-0.465). Conversely, no significant correlation was found between the level of BDNF and the presence of a manic or depressive state, and although HVA had a slightly stronger correlation than MHPG, the levels of neither of these were found to significantly correlate with the symptoms.Conclusion: These data suggest that peripheral MHPG levels (which is related to noradrenaline levels in the brain) could be used as a biomarker of mood states in BDI. The noradrenaline level in the brain is likely to reflect the clinical characteristics of the switch process in BDI, and has prognostic significance for the treatment of both manic and depressive states.Keywords: brain-derived neurotrophic factor (BDNF), monoamine, dopamine, homovanilic acid (HVA), depression, pathophysiology, mood disorder

Jinichi Hirano,1,2 Koichiro Watanabe,3 Takefumi Suzuki,1,4 Hiroyuki Uchida,1 Ryosuke Den,5 Taishiro Kishimoto,1 Takashi Nagasawa,5 Yusuke Tomita,4 Koichiro Hara,6 Hiromi Ochi,7 Yoshimi Kobayashi,1 Mutsuko Ishii,1 Akane Fujita,1 Yoshihiko Kanai,1 Megumi Goto,1 Hiromi Hayashi,1 Kanako Inamura,1 Fumiko Ooshima,1 Mariko Sumida,1 Tomoko Ozawa,1 Kayoko Sekigawa,1 Maki Nagaoka,1 Kae Yoshimura,1 Mika Konishi,1 Ataru Inagaki,1 Takuya Saito,8 Nobutaka Motohashi,9 Masaru Mimura,1 Yoshiro Okubo,8 Motoichiro Kato,11Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 2Ohizumi Hospital, Tokyo, Japan; 3Department of Psychiatry School of Medicine, Kyorin University, Tokyo, Japan; 4Inokashira Hospital, Tokyo, Japan; 5Komagino Hospital, Tokyo, Japan; 6Asai Hospital, Chiba, Japan; 7Kurumegaoka Hospital, Tokyo, Japan; 8Department of Psychiatry School of Medicine, Nippon Medical School, Tokyo, Japan; 9Department of Psychiatry, School of Medicine, University of Yamanashi, Yamanashi, JapanObjective: The use of an algorithm may facilitate measurement-based treatment and result in more rational therapy. We conducted a 1-year, open-label study to compare various outcomes of algorithm-based treatment (ALGO) for schizophrenia versus treatment-as-usual (TAU), for which evidence has been very scarce.Methods: In ALGO, patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were treated with an algorithm consisting of a series of antipsychotic monotherapies that was guided by the total scores in the positive and negative syndrome scale (PANSS). When posttreatment PANSS total scores were above 70% of those at baseline in the first and second stages, or above 80% in the 3rd stage, patients proceeded to the next treatment stage with different antipsychotics. In contrast, TAU represented the best clinical judgment by treating psychiatrists.Results: Forty-two patients (21 females, 39.0 ± 10.9 years-old) participated in this study. The baseline PANSS total score indicated the presence of severe psychopathology and was significantly higher in the ALGO group (n = 25; 106.9 ± 20.0) than in the TAU group (n = 17; 92.2 ± 18.3) (P = 0.021). As a result of treatment, there were no significant differences in the PANSS reduction rates, premature attrition rates, as well as in a variety of other clinical measures between the groups. Despite an effort to make each group unique in pharmacologic treatment, it was found that pharmacotherapy in the TAU group eventually became similar in quality to that of the ALGO group.Conclusion: While the results need to be carefully interpreted in light of a hard-to-distinguish treatment manner between the two groups and more studies are necessary, algorithm-based antipsychotic treatments for schizophrenia compared well to treatment-as-usual in this study.Keywords: algorithm, open-label clinical trial, measurement-based treatment, schizophrenia, treatment-as-usual