Validation of the sleep related items of the Non-motor Symptoms Questionnaire for Parkinson's disease (NMSQuest)

BackgroundThe Non-motor Symptoms Questionnaire (NMSQuest) is a recently developed questionnaire for the evaluation of non-motor symptoms in Parkinson's disease (PD) patients, which includes sleep disorders evaluation. The clinical validity of the questionnaire has not been explored.ObjectiveTo assess the performance of the sleep/fatigue domain of the NMSQuest against other sleep measures.MethodsSeventy PD patients were instructed to wear an actigraph and to fill in a sleep log over seven consecutive days in addition to the Parkinson's Disease Sleep Scale (PDSS) and the NMSQuest.ResultsPD patients who reported daytime sleepiness on NMSQuest obtained a significantly worse score on the PDSS sleepiness domain than PD patients who did not (12.0 ± 4.7 vs. 14.7 ± 3.4, p < 0.009). Patients reporting difficulty getting to sleep or staying asleep at night, showed lower scores on PDSS sleep quality domain than those without difficulties (15.8 ± 5.4 vs. 22.3 ± 4.6, p < 0.001). The presence of vivid dreams, acting out dreams and restlessness on NMSQuest correlated with PDSS and sleep log scores. Increased nocturnal activity was noted in subjects reporting acting out dreams. Furthermore, the number of positive answers to the sleep-fatigue questions of the NMSQuest correlated significantly with PDSS total score, sleep log total score and nocturnal activity measured by actigraphy.ConclusionNMSQuest sleep-fatigue domain identified appropriately sleep disturbances indicating its usefulness as a screening tool for sleep disorders in PD patients.     

Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep

ObjectiveTo examine the validity of a novel caffeine intake questionnaire and to examine the effects of caffeine on sleep in college students.MethodsOne-week, ad libitum behavior of 50 university students (28 female, 22 male; aged 20.9 ± 1.78 years) was examined with sleep logs, wrist actigraphy, and a novel daily questionnaire assessing caffeine intake at different times of day. Saliva samples were collected for caffeine assessment (questionnaire validation) and DNA extraction, and for analysis of a single nucleotide polymorphism in the adenosine receptor 2A (ADORA2A) gene.ResultsThe caffeine questionnaire was able to accurately predict salivary concentrations of caffeine (R² = 0.41, P < 0.001). Estimations of integrated salivary caffeine concentration during sleep were correlated with wake after sleep onset (WASO) most strongly in morning-type individuals (R² = 0.49; P < 0.001, ANOVA), less so in intermediate chronotypes (R² = 0.16; P < 0.001, ANOVA), and not significantly in evening-types (R² = 0.00098; P = 0.13, ANOVA). Using multivariate modeling methods we found that the ADORA2A genotype did not moderate the effects of caffeine on WASO, but did independently alter WASO such that those with the CC genotype had nearly three-times as much WASO as those with CT or TT.ConclusionsOur questionnaire was able to accurately predict salivary caffeine concentrations and helped to describe a novel relationship between the effects of caffeine on sleep and genotype and chronotype.     

Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy

Objectives: To compare subjective sleep perception, sleep architecture, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (PSP) to patients with Parkinson’s disease (PD).Methods: A comparative sleep study using the Parkinson’s Disease Sleep Scale (PDSS), the Mini-Mental State Examination (MMSE), and cardiorespiratory polysomnography on two consecutive nights with synchronized video recording. The study was undertaken in a sleep laboratory in a movement disorder center. Forty patients matched for age and cognition with probable PSP (n = 20, aged 71 ± 8 years, MMSE ? 24 in n = 7) and PD (n = 20, aged 69 ± 5 years, MMSE ? 24 in n = 8).Results: PDSS sum scores showed no difference between PSP and PD. PSP patients had significantly lower sleep efficiency (43.0 ± 15.0%) compared to PD patients (62.8 ± 19.1%) (p < 0.0008). Seventeen PSP patients and 19 PD patients had REM without atonia (RWA). Seven PSP patients and 13 PD patients had clinical RBD. The amount of RWA was lower in PSP (14.5 ± 17.3%) than in PD (44.6 ± 31.3%) (p < 0.0007). Eleven PSP and 11 PD patients were newly identified with sleep-disordered breathing (SDB).Conclusions: Polysomnographically recorded sleep is more severely impaired in PSP than in PD. PDSS ratings do not reflect the poorer sleep quality in PSP, possibly pointing to a specific neuropsychological profile. RWA and RBD are present in both neurodegenerative diseases. So far undetected SDB affects more than half of all patients in this study.     

Sleep disturbances in Malaysian patients with Parkinson's disease using polysomnography and PDSS

BackgroundSleep disturbances such as sleep fragmentation, sleep disordered breathing (SDB), periodic limb movements (PLM), excessive daytime somnolence (EDS) and insomnia are prevalent in Parkinson's disease (PD). However, studies in the Asian population are limited.MethodsThis was a cross-sectional study involving 46 Malaysians with PD using polysomnography (PSG) and standardized translated Parkinson's disease sleep scale (PDSS). Overnight PSG recordings, UPDRS and PDSS scores, and baseline demographic data were obtained.ResultsData from 44 patients were analysed. Thirty-six patients (81.8%) had PSG-quantified sleep disorders. Twenty-three (52.3%) had sleep fragmentation, 24 (54.6%) had SDB and 14 (32%) had PLM. EDS was present in 9.1%. Insomnia was reported by 31.8%. Patients with sleep fragmentation had significantly higher UPDRS scores and lower PDSS insomnia sub-scores. The UPDRS scores correlated negatively with the TST and sleep efficiency. All patients with EDS had SDB (p = 0.056). The PDSS insomnia sub-items correlated with sleep fragmentation on PSG.Conclusion: The prevalence of sleep disorders based on PSG and PDSS in our PD patients was high, the commonest being sleep fragmentation and SDB, while EDS was the least prevalent. Problem specific sub-items of the PDSS were more accurate in predicting the relevant PSG-related changes compared to the PDSS as a whole.     

Effects of nasal continuous positive airway pressure on panic disorder comorbid with obstructive sleep apnea syndrome

BackgroundsBoth obstructive sleep apnea syndrome (OSAS) and panic disorder (PD) are common disorders that often coexist. Continuous positive airway pressure (CPAP) has been established as the first-line treatment for OSAS. In this study, we examined the efficacy of CPAP on PD comorbid with OSAS by conducting a randomized crossover study using sham CPAP as control.MethodsPD patients (n = 12) with an apnea hypopnea index (AHI) of 20/h or higher completed the study. At baseline, the subjects were asked to write their own records pertaining to the frequency of attacks and their score on the panic disorder severity scale (PDSS), and then they participated in the randomized crossover trial period, which measured optimal CPAP and sham CPAP set at 4 cmH₂O during nighttime sleep for each 4-week assignment.ResultsThe frequency of panic attacks, total PDSS score, and the frequency of alprazolam use for alleviating the attack symptoms were significantly decreased during the optimal CPAP period than during the baseline period and the sham CPAP period. Among the PDSS subitems, the frequency of attacks, panic distress, work impairment, and social impairment showed significant improvements during the optimal pressure period.ConclusionOur results suggest that OSAS contributes to PD aggravation, and a combination of pharmaceutical treatment for PD and OSAS-specific treatments such as CPAP could be recommended for patients with PD comorbid with OSAS.     

Microsubthalamotomy improves sleep in patients affected by advanced Parkinson’s disease

BackgroundDeep brain stimulation of the subthalamic nucleus (STN-DBS) improves sleep in patients affected by Parkinson’s disease (PD). Since microsubthalamotomy (mSTN) shows positive effects on motor symptoms, it could improve sleep in PD patients. Our goals were: to assess the effects of mSTN on sleep in patients affected by advanced PD; and to look for a correlation between sleep and motor features after the neurosurgical procedure.MethodsFifteen patients who underwent bilateral STN-DBS were enrolled. Subjective sleep evaluation was assessed using the Parkinson’s Disease Sleep Scale (PDSS). Data on sleep schedule and presence of restless legs syndrome (RLS) were obtained. Objective sleep features were investigated by polysomnography (PSG). To evaluate the mSTN effect, we compared motor state and sleep features before and after the neurosurgical procedure, before the programmable pulse generator was switched on.ResultsmSTN had beneficial effects on motor state and sleep features. After the surgery, the mean total PDSS score increased from 84.0 ± 25.2 to 115.2 ± 16.6 (P < 0.001). PD patients reported longer total sleep time duration, decreased daytime sleepiness, and improvement in RLS symptoms. PSG data showed an increase in total sleep time and sleep efficiency with a decrease in wakefulness after sleep onset and arousal index. No correlation between motor improvements and sleep features modifications was observed after mSTN.ConclusionsmSTN improves sleep quality and ameliorates several sleep complaints, as well as motor symptoms, in advanced PD patients who have undergone STN-DBS.     

Sleep in essential tremor: a comparison with normal controls and Parkinson's disease patients

BackgroundRecent studies have shed light on non-motor features of ET, such as depressive symptoms and cognitive changes, which might be attributed to pathophysiological changes in the brains of ET patients. Given these brain changes, we explored sleep abnormalities in ET patients.MethodsSleep was assessed using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) in 120 ET cases, 120 normal controls, and 40 PD cases.ResultsThe mean ± SD (median) ESS score increased from normal controls (5.7 ± 3.7 (5.0)), to ET cases (6.8 ± 4.6 (6.0)), to PD cases (7.8 ± 4.9 (7.0)), test for trend p = 0.03. An ESS score >10 (an indicator of greater than normal levels of daytime sleepiness) was observed in 11 (9.2%) normal controls, compared to 27 (22.5%) ET cases and 10 (25.0%) PD cases (p = 0.008 when comparing all three groups, and p = 0.005 when comparing ET to normal controls). The global PSQI score was 7.8 ± 2.8 (7.5) in controls, 8.0 ± 3.3 (8.0) in ET cases, and 9.9 ± 3.9 (10.0) in PD cases. The ET case–control difference was not significant (p = 0.8), yet in a test for trend, PD cases had the highest PSQI score (most daytime sleepiness), followed by ET (intermediate), and lowest scores in controls (p = 0.02).ConclusionsSome sleep scores in ET were intermediate between those of PD cases and normal controls, suggesting that a mild form of sleep dysregulation could be present in ET.     

Sleep parameters associated with long-term outcome following subthalamic deep brain stimulation in Parkinson's disease

IntroductionWe aimed to investigate the effects of changes in sleep architecture on long-term clinical outcome in patients with Parkinson's disease (PD) who underwent deep brain stimulation of subthalamic nuclei (STN DBS).MethodsWe followed up eight PD patients before and three years after STN DBS surgery. In addition to clinical assessments, polysomnography (PSG) followed by multiple sleep latency tests was performed before and after STN DBS, while stimulator was ON and OFF.ResultsSubjective sleep latency was significantly decreased (P = 0.033) and sleep duration was increased (P = 0.041), as measured by Pittsburgh sleep quality index. Latency to REM sleep stage was shortened after surgery with STN DBS ON (P = 0.002). Index of central type of abnormal respiratory events was significantly increased while stimulator was ON (P = 0.034). Total number of major body movements was found to be increased when stimulator was turned OFF (P = 0.012). Among PSG data obtained during STN DBS ON, it was observed that duration of N3 sleep was negatively correlated with UPDRS scores at 1st (P = 0.038) and 3rd (P = 0.045) post-operative years. Among PSG variables during STN DBS OFF, durations of N3 sleep (P = 0.017) and REM sleep (P = 0.041) were negatively correlated with UPDRS scores at post-operative 1st year.ConclusionDisturbances in sleep architecture are associated with higher UPDRS scores and worse prognosis at 1st and 3rd post-operative years. Similar results obtained while stimulator was OFF at the end of 1st year support the presence of microlesion effect after STN DBS, which is probably not long lasting.     

Rapid eye movement sleep behaviour disorder in young- and older-onset Parkinson disease: a questionnaire-based study

BackgroundRapid eye movement sleep behavior disorder (RBD) is common in Parkinson disease (PD).ObjectivesTo determine the frequency of clinically probable RBD (cpRBD) in young-onset (21 to ⩽40 years; YOPD) and older-onset PD (>40 years; OOPD) and characterize its pattern.MethodsA total of 156 patients with PD (YOPD-51, OOPD-105) were clinically examined and the presence of RBD was diagnosed using the minimal criteria for diagnosis of RBD (International Classification of Sleep Disorders, ICSD-1). RBD screening questionnaire based on the minimal criteria was used. The bed-partners were also interviewed with Mayo sleep questionnaire. Other scales included Unified Parkinson Disease Rating Scale part III (UPDRS III), Hoehn & Yahr stage, Mini Mental Status Examination, Pittsburgh Sleep Quality Index, Parkinson Disease Sleep Scale, Epworth Sleep Scale, Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale.ResultscpRBD was diagnosed in 30 (19.2%) patients, majority being OOPD rather than YOPD (86.7% vs 13.3%; P = 0.01). The frequency of RBD was significantly higher (P = 0.016) in OOPD (24.8%) compared to those with YOPD (7.8%). Most often (72.4%) RBD occurred after the onset of parkinsonian symptoms. RBD was independently associated with higher global PSQI scores, total ESS scores and total PDSS scores after adjusting for the effects of age, gender, Hoehn & Yahr stage and duration of illness.ConclusionsPatients with RBD were older with later-onset motor symptoms, a more advanced stage, poorer sleep quality, and more frequent daytime sleepiness. Older-onset PD had a higher frequency of RBD than young-onset PD.     

rs2070424 of the SOD1 gene is associated with risk of Alzheimer's disease

ObjectiveOxidative stress plays an important role in Alzheimer's disease (AD) etiopathogenesis. There were several studies that showed impaired antioxidant defense system (ADS) enzymes expression or activity in AD patients. There are only few studies evaluating the importance of ADS gene single nucleotide polymorphisms (SNPs) as risk factors of AD. We evaluated association between chosen SNPs of the enzymes of the ADS and risk of AD.MethodsWe included 400 AD patients and 402 healthy controls. We studied rs1041740, rs4998557 and rs2070424 of the SOD1 gene, rs2855116, rs5746136 and rs4880 of the SOD2 gene and rs3448, rs1050450 and rs1800668 of the GPx-1 gene (real time PCR). To determine the APOE gene common polymorphism, two single-nucleotide polymorphisms (SNPs; NCBI SNPs rs429358 and rs7412) were genotyped (TaqMan assays, Applied Biosystems [ABI], Foster City, CA, USA). The genotype and gender frequencies were compared between the studied groups by the χ² test and mean age by the t-Student test.ResultsAmong all studied SNPs only rs2070424 of the SOD1 gene was a protective factor for AD in an additive (OR = 0.47; 95% CI = 0.30–0.74, p = 0.001) and recessive (OR = 0.47; 95% CI = 0.30–0.75, p = 0.002) models including age, gender and APOE gene status.Conclusionsrs2070424 polymorphism of the SOD1 gene is a risk factor for AD in Polish population. Allel G and genotype AG and GG are protective factors for AD.     

Risk factors of stroke and −717A > G (rs2794521) CRP gene polymorphism among stroke patients in West Pomerania province of Poland

Background and purposeSome of the risk factors of ischaemic stroke influence the development of atherosclerosis, which is a significant cause of vascular incidents. An inflammatory component plays a role in pathogenesis of both atherosclerosis and atrial fibrillation, the most important risk factor of embolic strokes. C-reactive protein (CRP) concentration in blood reflects the inflammatory process. Concentration of this protein depends on the CRP gene polymorphism. The aim of the study was to assess the relationship between selected risk factors of stroke and variant of −717A > G (rs2794521) CRP gene polymorphism in population of West Pomerania Province of Poland.Materials and methodsThere were 125 consecutive patients with ischaemic stroke analysed, who met the inclusion and exclusion criteria. In all patients, −717A > G CRP gene polymorphism was genotyped and analysed in relation to selected stroke risk factors.ResultsPrevalence of type 2 diabetes was lower in patients with AA genotype of −717A > G CRP gene polymorphism than in patients with other alleles (p = 0.017). Subjects with GG genotype had significantly higher concentration of CRP comparing to AG genotype (p = 0.023). No correlation was found between −717A > G CRP gene polymorphism and the lipid profile and other selected risk factors of stroke.ConclusionsIn patients with ischaemic stroke in West Pomerania Province, the GG genotype of −717A > G CRP gene polymorphism is associated with significantly higher CRP concentration in relation to AG genotype. Patients with AA genotype may be characterised by lower prevalence of type 2 diabetes.     

The relation between abnormal behaviors and REM sleep microstructure in patients with REM sleep behavior disorder

ObjectiveTo investigate the temporal relation between rapid eye movement (REM) sleep microstructure (REMs, EMG activity) and motor events in REM sleep behavior disorder (RBD).MethodsPolysomnographic records of eight patients with RBD were analyzed and compared with those of eight sex- and age-matched controls. We examined sleep microstructure for REM sleep with and without REMs and phasic chin EMG activity and their temporal relation to motor events on video.ResultsAll types of motor events were either more frequent in RBD patients than in controls (P ? 0.007) or present solely in RBD patients. In RBD, major motor events were significantly more frequent during REM sleep with REMs than during REM sleep without REMs (violent, 84.0% vs. 16.0%, P < 0.001; complex/scenic behavior, 78.1% vs. 23.2%, P < 0.001; major jerks, 77.5% vs. 20.3%, P < 0.001), whereas minor motor activity was evenly distributed (54.1% vs. 45.9%, P = 0.889). Controls showed predominantly minor motor activity with rare myoclonic body jerks. The distribution of motor events did not differ between REM sleep with and without REMs (40.9% vs. 59.1%, P = 0.262).ConclusionsIn RBD, major motor activity is closely associated with REM sleep with REMs, whereas minor jerks occur throughout REM sleep. This finding further supports the concept of a dual nature of REM sleep with REMs and REM sleep without REMs and implies a potential gate control mechanism of REM sleep with REMs for the manifestation of elaborate or violent behaviors in RBD.     

Detecting health disparities among Caucasians and African-Americans with epilepsy

ObjectiveThe aim of the study was to determine whether African-Americans and Caucasians who receive care at a tertiary epilepsy center can be distinguished on a variety of demographic, clinical, and psychosocial variables.MethodsWe surveyed 111 consecutive patients followed at a tertiary epilepsy center.ResultsOn univariate analysis, African-Americans had significantly more seizures (P = 0.03), lower scores on the Beliefs About Medicines Questionnaire—Specific (Necessity minus Concerns) (BMQ-S) (P = 0.01), and higher scores on the BMQ—General (BMQ-G) (P = 0.02). In binary logistic regression with race as the target variable, higher seizure frequency remained significantly associated with being African-American (P = 0.04). After ordinal regression with seizure frequency as the target variable, being African-American (P = 0.04) and higher BMQ-G scores (P = 0.02) remained significantly associated with increased seizure frequency.ConclusionCompared with Caucasians, African-Americans have higher seizure frequency and scores on the BMQ indicating a higher mistrust of medications. Aside from race, attitudes toward medications are also independently associated with seizure control.     

Degree of pineal calcification (DOC) is associated with polysomnographic sleep measures in primary insomnia patients

ObjectiveMelatonin plays a key role in the proper functioning of the circadian timing system (CTS), and exogenous melatonin has been shown to be beneficial in cases of CTS and sleep disturbances. Nevertheless, the concept of “melatonin deficit” has yet to be defined. The aim of our study was, therefore, to determine the relationship between the degree of pineal calcification (DOC) and a range of sleep parameters measured objectively using polysomnography (PSG).MethodsA total of 31 outpatients (17 women, 14 men, mean age 45.9 years; SD 14.4) with primary insomnia were included in our study. Following an adaptation night, a PSG recording night was performed in the sleep laboratory. Urine samples were collected at predefined intervals over a 32-h period that included both PSG nights. The measurement of 6-sulphatoxymelatonin (aMT6s) levels was determined using ELISA. DOC and volume of calcified pineal tissue (CPT) and uncalcified pineal tissue (UPT) were estimated by means of cranial computed tomography.ResultsUPT was positively associated with 24-h aMT6s excretion (r = 0.569; P = 0.002), but CPT was not. After controlling for age, aMT6s parameters, CPT, and UPT did not correlate with any of the PSG parameters evaluated. In contrast, DOC was negatively associated with REM sleep percentage (r = ?0.567, P = 0.001), total sleep time (r = ?0.463, P = 0.010), and sleep efficiency (r = ?0.422, P = 0.020).ConclusionDOC appears to be a superior indicator of melatonin deficit compared to the absolute amount of melatonin in the circulation. High DOC values indicate changes predominantly in the PSG parameters governed by the circadian timing system. DOC may thus serve as a marker of CTS instability.     

The SNP rs1625579 in miR-137 gene and risk of schizophrenia in Chinese population: A meta-analysis

BackgroundSchizophrenia is a severe psychiatric disorder with a high heritability. A single nucleotide polymorphism (SNP) rs1625579 (G/T; T is the common and presumed risk allele) within an intron of miR-137 gene has been recently suggested to contribute to the susceptibility to schizophrenia by a large-scale genome-wide association study (GWAS) in a sample of predominantly European ancestry. However, subsequent genetic association studies in Chinese population yielded inconsistent results.MethodsA meta-analysis reporting the association between rs1625579 and schizophrenia in Chinese population was carried out, pooling 4 eligible case–control studies involving 2847 patients and 3018 controls.ResultsThis meta-analysis demonstrated a significant association between rs1625579 and schizophrenia under the allele model [T versus G, odds ratio (OR):1.20, 95% confidence interval (CI): 1.06–1.36] and the recessive model (TT versus GT + GG; OR: 1.19; 95% CI: 1.04–1.37). Additionally, a marginal significant association under the additive model (TT versus GG; OR: 1.64; 95% CI: 1.00–2.69) was observed. However, no significant association was observed under the dominant model (TT + GT versus GG; OR: 1.58; 95% CI: 0.97–2.59).ConclusionsThis meta-analysis suggested that the SNP rs1625579 in miR-137 gene might be involved in schizophrenia susceptibility in Chinese Han population.     

Clinical significance of night-to-night sleep variability in insomnia

ObjectivesTo evaluate the clinical relevance of night-to-night variability of sleep schedules and insomnia symptoms.MethodsThe sample consisted of 455 patients (193 men, mean age = 48) seeking treatment for insomnia in a sleep medicine clinic. All participants received group cognitive behavioral therapy for insomnia (CBTI). Variability in sleep parameters was assessed using sleep diary data. Two composite scores were computed, a behavioral schedule composite score (BCS) and insomnia symptom composite score (ICS). The Insomnia Severity Index, the Beck Depression Inventory, and the Morningness–Eveningness Composite Scale were administered at baseline and post-treatment.ResultsResults revealed that greater BCS scores were significantly associated with younger age, eveningness chronotype, and greater depression severity (p < 0.001). Both depression severity and eveningness chronotype independently predicted variability in sleep schedules (p < 0.001). Finally, CBTI resulted in reduced sleep variability for all sleep diary variables except bedtime. Post-treatment symptom reductions in depression severity were greater among those with high versus low baseline BCS scores (p < 0.001).ConclusionsResults suggest that variability in sleep schedules predict reduction in insomnia and depressive severity following group CBTI. Schedule variability may be particularly important to assess and address among patients with high depression symptoms and those with the evening chronotype.     

The effects of ramelteon in a first-night model of transient insomnia

ObjectiveTo evaluate the efficacy and safety of ramelteon, a highly selective MT₁/MT₂ melatonin receptor agonist, for the treatment of transient insomnia in adults.MethodsIn a randomized, double-blind, placebo-controlled, multi-center study, 289 adults naive to a sleep laboratory environment were randomized to receive a single nighttime dose of ramelteon 8 mg, 16 mg, or placebo. The primary variable was latency to persistent sleep measured by polysomnography. Additional objective and subjective sleep parameters as well as next-morning residual effects were assessed.ResultsRamelteon 8 mg treatment significantly reduced latency to persistent sleep compared with placebo (12.2 min vs. 19.7 min, P = 0.004). Total sleep time was significantly increased with both ramelteon 8 mg (436.8 min, P = 0.009) and ramelteon 16 mg (433.1 min, P = 0.043) compared with placebo (419.7 min). Ramelteon did not alter sleep architecture, and no significant next-morning residual effects were detected. The incidence of adverse events was similar for the ramelteon and placebo groups and most were considered mild or moderate.ConclusionRamelteon 8 mg significantly decreased latency to persistent sleep and increased total sleep time, with no significant next-morning psychomotor, memory, or cognitive effects in this first-night model of transient insomnia.     

Genetic and serum biomarker evidence for a relationship between TNFα and PTSD in Vietnam war combat veterans

BackgroundPosttraumatic stress disorder (PTSD) is associated with increased inflammation and comorbid medical conditions. However, study findings for individual inflammatory marker levels have been inconsistent. Some research suggests that resilience may play a role in decreased inflammation. A polymorphism in the promoter region of the tumor necrosis factor α gene (TNFα), TNFA −308 (rs1800629) is associated with psychiatric illness but its role in PTSD is yet to be elucidated.ObjectiveThis study investigates a key inflammatory marker, TNFα, for its role in PTSD severity.MethodIn a cohort of trauma-exposed Vietnam War veterans (n = 299; 159 cases, 140 controls) TNF α serum levels and TNFα polymorphism rs1800629 were correlated with PTSD severity and resilience scores.ResultsThe polymorphism was associated with PTSD severity (p = 0.045). There were significant group differences between cases and controls with regards to serum TNFα levels (p = 0.036). Significant correlations were found between PTSD severity and elevated TNFα levels (r = 0.153; p = 0.009), and between resilience and decreased TNFα levels at a trend level (p = 0.08) across the entire cohort. These relationships were non-significant after controlling for covariates. In the PTSD diagnostic group, a correlation of TNFα and PTSD severity was observed on a trend level (p = 0.06), the relationship between TNFα and resilience remained non-significant.ConclusionsTo our knowledge, this is the first time rs1800629 has been investigated in PTSD contributing to a growing body of literature that identifies the GG as a risk genotype for psychiatric disorders in Caucasian cohorts. However, more research is needed to replicate our results in larger, equally well-characterized cohorts. The relationship between serum TNFα levels and PTSD severity and resilience requires further investigation.     

GABRG2 rs211037 polymorphism and epilepsy: A systematic review and meta-analysis

PurposeThe gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene encodes the GABRγ2 protein, which has been implicated in susceptibility to epilepsy. Several studies have examined a possible link between the exonic GABRG2 rs211037 locus and susceptibility to febrile seizure (FS) and idiopathic generalized epilepsy (IGE), however results have been inconclusive. We therefore performed a systematic review and meta-analysis to examine whether this polymorphism is associated with FS or IGE.MethodsEight studies comprising 1871 epilepsy patients and 1387 controls, which evaluated association of the GABRG2 rs211037 polymorphism with susceptibility to epilepsy, were included in this meta-analysis. Meta-analysis was carried out separately for FS and IGE.ResultsMeta-analysis showed a significant association between this polymorphism and susceptibility to FS in a codominant (TT vs. CC, OR 0.47, 95% CI 0.30–0.73, p = 0.0008 and TT vs. CT, OR 0.59, 95% CI 0.42–0.83, p = 0.003) and dominant (OR 0.54, 95% CI 0.39–0.75, p = 0.0002) genetic models, influenced by two studies with small sample size. Neither allele nor genotype association was observed with IGE.ConclusionThis study showed significant association of GABRG2 rs211037 with susceptibility to FS, caused by two studies with small sample sizes, however the possibility of false positive results due to the effect of significant studies for FS cannot be excluded. Future studies with larger sample sizes of these patients are suggested to verify the results.     

Double-blind,randomized, placebo controlled trial on the effect of 10 days low-frequency rTMS over the vertex on sleep in Parkinson’s disease

ObjectiveA recent report indicates repetitive transcranial magnetic stimulation (rTMS) improves sleep in Parkinson’s disease (PD). The aim of this work is to evaluate the effect of 10 days rTMS on sleep parameters in PD patients.MethodsDouble-blind, placebo-controlled design. Eighteen idiopathic PD patients completed the study. Sleep parameters were evaluated through actigraphy and the Parkinson’s Disease Sleep Scale (PDSS), along with depression (Hamilton Depression Rating Scale, HDS), and the Unified Parkinson’s Disease Rating Scale (UPDRS). Evaluations were carried out before treatment with rTMS (pre-evaluation, PRE), after the rTMS treatment programme (post-evaluation, POST), and one week after POST (POST-2). Nine PD patients received real rTMS and the other 9 received sham rTMS daily for 10 days, (100 pulses at 1 Hz) applied with a large circular coil over the vertex.ResultsStimulation had no effect over actigraphic variables. Conversely PDSS, HDS, and UPDRS were significantly improved by the stimulation. Notably, however, these changes were found equally in groups receiving real or sham stimulation.ConclusionsrTMS, using our protocol, has no therapeutic value on the sleep of PD patients, when compared to appropriate sham controls. Future works assessing the possible therapeutic role of rTMS on sleep in PD should control the effect of placebo.