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We describe a case of parasomnia overlap disorder (POD) caused by paroxetine. Some reports have associated antidepressants such as selective serotonin reuptake inhibitors (SSRI) with rapid eye movement sleep behavior disorder. However, to the best of our knowledge, there have been no reports of POD caused by paroxetine. We diagnosed POD in a patient taking paroxetine using video-polysomnography (v-PSG) and then confirmed the improvement of POD symptoms by v-PSG after discontinuing the drug. [ABSTRACT FROM AUTHOR]

The clock gene ( CLOCK) is considered to be a good candidate gene for the pathophysiology of mood disorders, including bipolar disorder (BP) and major depressive disorder (MDD). rs1801260 (T3111C) has been detected at position 3111 in the CLOCK mRNA 3' untranslated region, and was reported to be associated with a substantial delay in preferred timing for activity and sleep in a human study. As for function, rs1801260 has been speculated to affect mRNA. Therefore, the authors investigated the association between the three tagging single-nucleotide polymorphisms (SNPs) (rs3736544, rs1801260, and rs3749474) in CLOCK and risk of BP (n == 867) and MDD (n == 139) compared to controls (n == 889) in the Japanese population. In addition, we also performed an updated meta-analysis of nine published, genetic association studies investigating the relationship between rs1801260 and mood disorder risk, comprising 3321 mood disorders cases and 3574 controls. We did not detect any associations between tagging SNPs in CLOCK and BP or MDD in the allele, genotype, or haplotype analysis (global pBP == .605 and global pMDD == .211). Moreover, rs1801260 was also not associated with BP, MDD, or any mood disorders in the meta-analysis. In conclusion, these data suggest that CLOCK does not play a major role in the pathophysiology of mood disorders. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

Several recent investigations reported that the serotonin 2A receptor gene ( HTR2A) was associated with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder. There have also been two reported association analyses of HTR2A with SSRI response in Japanese MDD patients, but the results were rather inconsistent and both studies had the problem of small sample sizes. Therefore, we conducted a replication association study using a sample larger than those in the two original Japanese studies (265 MDD patients), and found that four SNPs, two functional SNPs (-A1438G: rs6311 and T102C: rs6313) and two SNPs (rs7997012 and rs1928040) in HTR2A, were associated with the therapeutic response to SSRIs. HTR2A was associated with the therapeutic response SSRIs in Japanese MDD patients in a haplotype-wise analysis ( P = 0.0136), and a significant association between rs1928040 in HTR2A and SSRI response was detected in MDD ( P = 0.0252). However, this significance disappeared after Bonferroni correction ( P = 0.101). In conclusion, we suggest that HTR2A may play an important role in the pathophysiology of the therapeutic response to SSRIs in Japanese MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples. [ABSTRACT FROM AUTHOR]

Background/Aim: Nitric oxide has been reported to play a role in neural transmitter release and N-methyl-D-aspartate receptor activation, as well as to be related to oxidative stress. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BP). In addition, several lines of evidence support an association between abnormalities in neuronal nitric oxide synthases (nNOS) and mood disorders. Therefore, we studied the association of nNOS gene (NOS1) and mood disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients. Materials and Methods: Using a single nucleotide polymorphism (SNP; rs41279104, also called ex1c), we conducted a genetic association analysis of case-control samples (325 MDD patients, 154 BP patients and 807 controls) in the Japanese population. In addition, we performed an association analysis between NOS1 and the efficacy of fluvoxamine treatment in 117 MDD patients. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D (Structured Interview Guide for the Hamilton Rating Scale for Depression) score within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Results: We did not detect a significant association between NOS1 and MDD, BP or the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis. Conclusions: We did not detect an association between only one marker (rs41279104) in NOS1 and Japanese mood disorder patients and fluvoxamine response, but sample sizes were probably too small to allow a meaningful test. Moreover, because we did not perform an association analysis based on linkage disequilibrium and a mutation scan of NOS1, a replication of the study using a larger sample and based on linkage disequilibrium may be required for conclusive results. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Several lines of evidence suggest that abnormalities in the serotonin system may be related to the pathophysiology of schizophrenia. The 5-HT7 receptor is considered to be a possible schizophrenia-susceptibility factor, based on findings from binding, animal, postmortem, and genomewide linkage studies. In this study, we conducted linkage disequilibrium (LD) mapping of the human 5-HT7 receptor gene (HTR7) and selected four ‘haplotype-tagging (ht) SNPs’. Using these four htSNPs, we then conducted an LD case-control association analysis in 383 Japanese schizophrenia patients and 351 controls. Two htSNPs (SNP2 and SNP5) and haplotypes were found to be associated with schizophrenia. A promoter SNP (SNP2) was further assessed in a dual-luciferase reporter assay, but it was not found to have any functional relevance. Although we failed to find an actual susceptibility variant that could modify the function of HTR7, our results support the supposition that HTR7 is a susceptibility gene for schizophrenia in this ethnic group.Neuropsychopharmacology (2006) 31, 866–871. doi:10.1038/sj.npp.1300901; published online 28 September 2005 [ABSTRACT FROM AUTHOR]

Procrastination behavior has been reportedly associated with the evening preference. This study aimed to evaluate its difference between patients with circadian rhythm sleep–wake disorders with phase delay (CRSWDswPD) and healthy controls in terms of evening preference and comorbid psychiatric disorders. Thirty patients with CRSWDswPD and 29 healthy participants were included. In both groups, the general procrastination scale (GPS), Beck Depression Inventory (BDI), and Morningness–Eveningness Questionnaire (MEQ) were administered. Additionally, Adult ADHD Self-Report Scale (ASRS) and autism spectrum quotient (AQ) were also assessed in the patient group. Unexpectedly, GPS was not statistically different between patients with CRSWDswPD and healthy controls. GPS was significantly higher with lower MEQ in the healthy group, whereas the opposite tendency was observed in the patient group. Higher AQ, ASRS, and BDI tended to be associated with higher GPS in the patient group, with the first two being statistically significant. The results suggest that general procrastination is not significantly associated with CRSWDswPD, although it is associated with evening preference in healthy participants. Procrastination in the patient group may be associated with developmental disorders or depression tendencies. Future studies should include simultaneous measurement of circadian markers, other behavioral assessments, a larger population, and untreated patients. [ABSTRACT FROM AUTHOR]

The relationship between daytime napping and depression remains debatable. Thus, we investigated whether daytime napping is associated with depressive symptoms in patients with bipolar disorder. In a cross-sectional study, we enrolled 204 outpatients with bipolar disorder who were participants in the Association between Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. Each participant's daytime napping was measured using an actigraph over 7 consecutive days. Depressive symptoms were evaluated using the Montgomery–Åsberg Depression Rating Scale, and scores of ≥8 points were considered indicative of a depressed state. One-hundred and ten (53.9 %) participants were depressed. In multivariable logistic regression analysis, as the number of nap days, number of naps per day, and nap duration increased, the odds ratio (OR) for depressed state significantly increased. Additionally, compared to the participants who did not nap, the participants who napped on five or more days a week or who had an average nap duration over 60 min had more than three times higher ORs in the depressed state (number of nap days: OR, 3.66; 95 % confidence interval [CI], 1.32–10.17; nap duration: OR, 3.14; 95 % CI, 1.12–8.81). We found a significant and independent association between daytime napping and depressive symptoms in patients with bipolar disorder. Further studies are warranted to identify the effect of short napping on depressive symptoms in patients with bipolar disorder. • Over 80 % patients with bipolar disorder took at least one nap per week. • Daytime napping was significantly associated with increased depressed state. • The association was independent of several potential confounding factors. [ABSTRACT FROM AUTHOR]

Aim: Sleep disturbance, a core feature of bipolar disorder, is closely associated with mood symptoms. We examined the association between actigraphy sleep parameters and mood episode relapses in patients with bipolar disorder. Methods: This prospective cohort study analyzed 193 outpatients with bipolar disorder who participated in the Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. The participants' sleep was objectively evaluated via actigraphy over seven consecutive days for the baseline assessment and then at the 2‐year follow‐up appointment for mood episode relapses. The actigraphy sleep parameters were presented using the mean and variability (standard deviation) of each sleep parameter for 7 days. Results: Of the 193 participants, 110 (57%) experienced mood episodes during follow‐up. The participants with higher variability in total sleep time had a significantly shorter mean estimated time to mood episode relapses than those with lower variability (12.5 vs. 16.8 months; P < 0.001). The Cox proportional hazards model, when adjusted for potential confounders, demonstrated that variability in total sleep time was significantly associated with an increase in the mood episode relapses (per hour; hazard ratio [HR], 1.407; 95% confidence interval (CI), 1.057–1.873), mainly in the depressive episodes (per hour; HR, 1.477; 95% CI, 1.088–2.006). Conclusions: Our findings suggest that consistency in sleep time might be useful, as an adjunct therapy, in preventing the recurrence or relapse of mood episodes in bipolar disorder. [ABSTRACT FROM AUTHOR]

Circadian activity rhythm disruption is a core feature in bipolar disorder. We investigated whether light exposure in daily life is associated with circadian activity rhythms in patients with bipolar disorder. In a cross-sectional study, we enrolled 194 outpatients with bipolar disorder who were participants of the Association between Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. The participants' physical activity and daytime illuminance were measured using an actigraph over 7 consecutive days. Nighttime illuminance in the bedroom was measured using a portable photometer. Circadian activity rhythm parameters were calculated using cosinor analysis and a nonparametric circadian rhythm analysis. The median daytime illuminance and nighttime illuminance were 224.5 lx (interquartile range, 154.5–307.5 lx) and 2.3 lx (0.3–9.4 lx), respectively. Multivariable linear regression analysis, adjusted for potential confounding factors, showed that higher daytime illuminance was significantly associated with higher amplitude and most active continuous 10-hour period, advanced acrophase, higher interdaily stability, and lower intradaily variability. Higher nighttime illuminance was significantly associated with lower relative amplitude, delayed onset of the least active continuous 5-hour period, and higher intradaily variability. As this was a cross-sectional study, the results do not necessarily imply that light exposure alters circadian activity rhythms. Daytime light exposure was associated with a positive effect and nighttime light exposure with a negative effect on circadian activity rhythms in bipolar disorder. • Circadian disruption is a core feature of bipolar disorder. • Daytime light was associated with a positive effect on circadian activity rhythms. • Nighttime light was associated with a negative effect on circadian activity rhythms. • The associations was independent of several potential confounding factors. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Recently, we detected that the prokineticin 2 receptor gene was associated with not only major depressive disorder (MDD) but also methamphetamine dependence. Therefore, it is possible that mood disorders and drug addiction have shared susceptibility genes. The translin-associated factor X gene (TSNAX)/disrupted-in-schizophrenia-1 gene (DISC1) has been associated with psychiatric disorders, including schizophrenia, MDD and bipolar disorder. TSNAX is located immediately upstream of DISC1 and has been shown to undergo intergenic splicing with DISC1. Based on this evidence, we hypothesized that TSNAX might be a good candidate gene for methamphetamine dependence. Methods: We conducted a case-control study of Japanese individuals (215 with methamphetamine dependence and 318 age- and sex-matched controls) with three tagging SNPs (rs1630250, rs766288 and rs6662926) selected by HapMap database. Results: rs1630250 was associated in males with methamphetamine dependence in the allele analysis (P-value: 0.0253). However, these results did not remain significant after Bonferroni correction to adjust for multiple comparisons (corrected P-value: 0.152). Conclusion: Our findings suggest that TSNAX does not play a role in methamphetamine dependence in the Japanese population. A replication study using larger samples needs to be conducted to obtain conclusive results. [Copyright &y& Elsevier]

Sleep disturbance is a core feature of bipolar disorder; hence, sleep must be accurately assessed in patients with bipolar disorder. Subjective sleep assessment tools such as sleep diary and questionnaires are often used clinically for assessing sleep in these patients. However, the insight into whether these tools are as accurate as objective tools, such as actigraphy, remains controversial. This cross-sectional study included 164 outpatients with a diagnosis of bipolar disorder, including patients who had euthymic and residual symptomatic periods. Objective sleep assessment was conducted prospectively using actigraphy for 7 consecutive days, whereas subjective sleep assessment was conducted prospectively using a sleep diary. The correlations were high and moderate between sleep diary and actigraphy when assessing the total sleep time and sleep onset latency, respectively (r = 0.81 and 0.47). These correlations remained significant after correction for multiple testing (both p < 0.001) and in both euthymic and residual symptomatic states (total sleep time: r = 0.86 and 0.77; sleep onset latency: r = 0.51 and 0.40, respectively). The median (interquartile ranges) of the percentage difference (sleep diary parameters minus actigraphy parameters divided by actigraphy parameter) in the total sleep time was relatively small (6.2% [−0.2% to 13.6%]). Total sleep time assessment using a sleep diary could be clinically useful in the absence of actigraphy or polysomnography. • Sleep disturbance is a core feature of bipolar disorder. • The total sleep time assessed by diary highly correlated with that by actigraphy. • Such correlation remained regardless of having a euthymic or symptomatic period. • The correlations between the questionnaire and actigraphy were low or non-existent. [ABSTRACT FROM AUTHOR]

• Self-harm was associated with the evening chronotype in bipolar disorder patients. • Of 205 patients with bipolar disorder, 36 (18%) had self-harmed in the past year. • Self-harm was most frequently via use of a sharp object or self-poisoning. Patients with bipolar disorder (BD) frequently self-harm, and this is strongly associated with subsequent suicide. This study investigated the association between chronotype and intentional self-harm in patients with BD. Two-hundred and five outpatients with BD participated in this cross-sectional study. Each participant's chronotype was evaluated using the Morningness-Eveningness Questionnaire, dividing the scores into three types: evening, 16–41 points; intermediate, 42–58 points; and morning, 59–86 points. Intentional self-harm over the past year were self-reported by questionnaire. Propensity score for evening chronotype was estimated from age, sex, socioeconomic factors, mood symptoms, total sleep time, age at the onset of BD, psychiatric inpatient history, family history of suicide, psychiatric comorbidity, and use of lithium. Thirty-six (18%) of the 205 participants reported self-harm. A substantially higher proportion of the evening chronotype group self-harmed compared to the other groups (evening, 37%; intermediate, 13%; morning 10%). In multivariable analysis adjusted for propensity score, the odds ratio (OR) for self-harming significantly increased from morning to intermediate to evening chronotype (ORs: morning, 1.00; intermediate, 1.56; evening, 3.61; P for trend = 0.038). This study was a cross-sectional and small sample size. Although a third factors, such as personality disorder or disrupted circadian rhythm, may have influenced, these findings suggest association between chronotype and intentional self-harm in BD patients. [ABSTRACT FROM AUTHOR]

Background: The minimum narcolepsy criteria "mean sleep latency (MSL) ≤8 min and ≥2 sleep onset rapid eye movement (REM) periods (SOREMPs) on polysomnography (PSG) and the multiple sleep latency test (MSLT)," according to The International Classification of Sleep Disorders, Third Edition (ICSD-3), are not specific to narcolepsy. Recently, the characteristic sleep stage sequences preceding SOREMPs in narcolepsy have received attention, but their diagnostic utility remains unclear.Methods: We retrospectively reviewed PSG/MSLT records and chart data for 102 Japanese patients with hypersomnia and at least one SOREMP. We examined the sporadic rates of two sleep stage sequences preceding the SOREMPs-wakefulness or stage 1 to REM (W/S1→R) and stage 2 to REM (S2→R)-comparing these between patient groups with narcolepsy type 1 (N = 28), narcolepsy type 2 (N = 19), and other hypersomnia (N = 55). We also examined the utility of three simple indices using the occurrence of W/S1→R SOREMPs for distinguishing between narcolepsy and other hypersomnia in patients who satisfied the minimum narcolepsy criteria.Results: W/S1→R SOREMPs were significantly more frequent in narcolepsy than in other hypersomnia, and this tendency was also observed even in the patients who satisfied the minimum narcolepsy criteria. The three indices had moderate sensitivities and specificities for distinguishing between narcolepsy and other hypersomnia in patients satisfying the minimum narcolepsy criteria.Conclusions: The W/S1→R pattern was observed significantly more frequently in narcolepsy than in other hypersomnia, suggesting it may help with differentiating narcolepsy from other hypersomnia in patients demonstrating the narcolepsy criteria, although its ability to do so may be modest. [ABSTRACT FROM AUTHOR]

Highlights: [•] The ESS and PSQI do not predict the diagnosis of OSA, PLMD, RBD, and narcolepsy. [•] The meta-analysis confirmed that the ESS has no value in identifying OSA. [•] The PSQI and ESS are more influenced by subjective rather than objective measures. [ABSTRACT FROM AUTHOR]

Abstract: Background: Several investigations have reported that abnormalities in circadian rhythms might be related to the pathophysiology of major depressive disorder (MDD) and the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). Recently, ubiquitin-specific peptidase 46 (USP46), a new molecule related to the circadian clock system, has been described. We conducted a case control study between seven tagging SNPs (rs10517263, rs17675844, rs6554557, rs12646800, rs2244291, rs10034164, rs346005) in the USP46 gene, MDD, and the SSRI therapeutic response in MDD in the Japanese population. Method: We recruited 432 MDD patients (202 males and 230 females) and 792 healthy controls (319 males and 473 females). Two hundred sixty-one of 432 MDD patients were treated with SSRIs (fluvoxamine, sertraline or paroxetine). Result: We detected an association between the USP46 gene and MDD in a haplotype analysis (rs2244291–rs10034164–rs346005 and rs12646800–rs2244291–rs10034164–rs346005). However, we did not find any association between the USP46 gene and SSRI response or remission in MDD in the Japanese population. Limitations: A replication study using larger samples may be required for conclusive results, since our sample size was small. Conclusions: Our results suggest that the USP46 gene might play a role in the pathophysiology of MDD in the Japanese population. [Copyright &y& Elsevier]

• Prevalence of obesity in 200 patients with bipolar disorders (BD) was 44%. • Night light was significantly associated with increased obesity in BD patients. • This association was independent of several potential confounding factors. Obesity and overweight are highly prevalent in individuals with bipolar disorder and are associated with a risk of developing not only physical but also mental problems. The current study aimed to determine the association between bedroom light exposure at night and obesity in individuals with bipolar disorder. This cross-sectional study enrolled 200 outpatients with bipolar disorder. The light intensity in the bedroom between bedtime and rising time was measured for seven consecutive nights using a portable photometer. Body mass index (BMI) was determined using self-reported height and weight, and obesity was defined as a BMI ≥ 25 kg/m2. The overall prevalence of obesity was 44%. In the multivariable logistic regression analysis adjusted for age, gender, use of psychiatric medications, sleep parameters, and physical activity, the odds ratio (OR) for obesity was significantly higher in the group exposed to an average light intensity ≥ 3 lux (n = 112) than in the group exposed to an average light intensity < 3 lux (n = 88) (OR, 2.13; 95% confidence interval, 1.19–4.21; P = 0.01). Furthermore, individuals exposed to an average light intensity ≥ 3 lux were significantly higher body weight (adjusted mean, 68.7 vs. 64.4 kg; P = 0.03) and BMI (adjusted mean, 25.6 vs. 24.2 kg/m2; P = 0.04) than those exposed to an average light intensity < 3 lux. A significant association was observed between bedroom light exposure at night and obesity in patients with bipolar disorder. Further longitudinal investigations are necessary to clarify this association. [ABSTRACT FROM AUTHOR]