S.P. Lam

Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK)☆

OBJECTIVES There are limited screening instruments for diagnosis of REM sleep behavior disorder (RBD) and none for quantifying the severity of disease. We aimed to validate a 13-item self-reported RBD questionnaire (RBDQ-HK) for diagnostic and monitoring purposes. METHODS Based on ICSD-II and our previous clinical and empirical work, the RBDQ-HK questionnaire was designed and administered in patients attending university-affiliated sleep clinic and psychiatric out-patient clinic, and subjects from the general population. ROC curve and exploratory factor analysis were employed to evaluate the scale, which had a score ranging from 0 to 100. RESULTS One hundred and seven RBD patients [mean age 62.6 (15.5) years; male 70.1%] and 107 control subjects [mean age 55.3 (9.0) years, male 57.9%] completed the questionnaire. The diagnoses of all the study subjects were independently ascertained by clinical interview and PSG. RBD patients had a significantly higher total RBDQ-HK score [mean (s.d.): 32.1 (16.1), range 3-71] than the control group [9.5 (10.2), range 0-55] (p<0.005). The RBDQ-HK demonstrated robust psychometric properties with moderate sensitivity (82.2%), specificity (86.9%), positive predictive value (PPV; 86.3%), and negative predictive value (NPV; 83.0%), high internal consistency and test-retest reliability. Exploratory factor analysis revealed two components (dream-related and behavioral factors) that corresponded to the essential clinical features of RBD. The best cut-off for total score (range 0-100) was at 18/19 and the best cut-off for factor 2 (behavioral factors including sleep talking, shouting, limb movements and sleep-related injuries, range 0-70) was at 7/8. CONCLUSIONS The RBDQ-HK has satisfactory validity and reliability as a measure of clinical RBD symptoms and severity. It may serve as an effective tool for diagnosis and evaluation of the disease course to facilitate future clinical and research studies.

Long-term outcomes and predictors of chronic insomnia: A prospective study in Hong Kong Chinese adults

OBJECTIVES We aimed to determine the longitudinal course and outcome of chronic insomnia in a five-year prospective study in Hong Kong Chinese adults. METHODS Two thousand three hundred and sixteen middle-aged adults (53.3% females, 46.3 ± 5.1 years old at follow-up) were recruited at baseline and follow-up. Participants were divided into three groups: non-insomnia, insomnia symptoms, and insomnia syndrome (insomnia symptoms plus daytime symptoms). Upper airway inflammatory diseases, mental problems, and medical problems were additionally assessed at follow up. RESULTS The incidence of insomnia (symptoms and syndrome) was 5.9%. The persistence rate of insomnia syndrome was 42.7% for insomnia syndrome and 28.2% for insomnia symptoms. New incidence of insomnia was associated with younger age, unemployment, and daytime symptoms, while persistence of insomnia was associated with female sex, lower education level, and daytime symptoms at the baseline (p<0.05). Baseline insomnia syndrome was significantly associated with upper airway inflammatory diseases (including asthma and laryngopharyngitis; adjusted OR=1.97-17.9), mental problems, and medical conditions (including arthritis, psychiatric disorders, chronic pain, and gastroesophageal reflux disease; AOR=2.29-3.77), whereas baseline insomnia symptoms were associated with poor mental health (AOR=2.43), psychiatric disorders (AOR=2.39), and chronic pain (AOR=2.95). CONCLUSIONS Chronic insomnia is a common problem with considerable persistence and incidence rates among middle-aged Chinese adults. Insomnia syndrome has a higher persistence rate with more mental and medical comorbidities when compared with insomnia symptoms without daytime consequences.

Familial aggregation of narcolepsy.

OBJECTIVES To determine the familial aggregation of narcolepsy from perspectives of clinical symptomatology, polysomnographic data, and human leukocyte antigen (HLA) typing. METHODS This was a Family study at the University-affiliated hospital. The participants were narcolepsy probands and their first degree relatives, and, also, age and sex matched unrelated healthy controls. Interventions were not applicable. MEASUREMENTS AND RESULTS All study subjects underwent structured interviews, overnight polysomnography followed by a multiple sleep latency test (MSLT), and HLA typing. Altogether, 33 probands and 81 first degree relatives (response rate 65%) were recruited. Among the relatives, 12.3% were diagnosed with narcolepsy and 39.5% had narcolepsy spectrum as defined by unexplained abnormal MSLT (shortened MSL and SOREMP) results. The relative risk of narcolepsy in first degree relatives was 361.8. Familial aggregation of narcolepsy symptoms, excessive daytime sleepiness, HLA status, abnormal MSLT, and nocturnal polysomnographic findings were observed. CONCLUSIONS The familial risk of narcolepsy among first degree relatives is much higher than previously reported. There exists a spectrum of narcolepsy features among relatives, ranging from full clinical tetrads to asymptomatic abnormal MSLT findings.

Noncontinuous use of antidepressant in adults with major depressive disorders – a retrospective cohort study

Noncontinuous antidepressant use is frequently observed in clinical practice despite the standard recommendation of at least 6–9 months of continuous treatment. The problem may be more serious in Chinese populations where stigmatization is common. This retrospective cohort study investigated the rate of noncontinuous antidepressant use and subsequent rate of relapse and recurrence in psychiatric Chinese outpatients by examining the prescription records, electronic medical records, and written medical records. Factors associated with noncontinuous antidepressant use were also identified.

Family conflict and lower morning cortisol in adolescents and adults: modulation of puberty.

We aimed to explore the association between family conflict and HPA axis activity, especially with respect to the potential modulating effect of puberty. A total of 205 adolescents and 244 adult parents were recruited. Family conflict was assessed by the family conflict subscale of the Family Environmental Scale and serial salivary cortisol was measured in all participants. A marginally lower AUCg at 30 minutes after wake up in the morning and a significant lower AUCg at 60 minutes and 90 minutes in adult parents with high family conflict was found when compared to those with low family conflict. In adolescents, there were significant interaction effects between pubertal status and family conflict on AUCg (interaction p values <0.05). Among the adolescents with low family conflict, those at late/post pubertal status had higher AUCg than their pre/early pubertal counterparts but this difference was not observed in the adolescents with high family conflict. Adverse family environment is associated with HPA axis dysfunction in adults and late/post pubertal adolescents and pubertal maturation plays a critical role in modulating the association between family environment and HPA axis function.

Identification of a Novel Serum Peptide Associated with Narcolepsy.

Narcolepsy is a crippling sleep disorder with a prevalence rate of 0.03–0.16% in the general population across the world [1]. It has serious impacts on academic, family, mental, and social functioning [2,3]. Apart from the hallmark clinical symptoms of daytime sleepiness and cataplexy, overnight polysomnography (PSG) followed by multiple sleep latency test (MSLT) and the measurement of hypocretin level in cerebrospinal fluid (CSF) have been included in the international diagnostic criteria of narcolepsy [4]. However, PSG is a costly and timely procedure with long waiting queues in some part of the world. In addition, CSF hypocretin level involves invasive lumbar puncture at which a number of Chinese subjects refuse [1,3]. Other serum tests, such as HLA-typing for DQB1*0602, are neither specific nor sensitive enough for diagnosing narcolepsy. In this study, we aimed at looking into the serum analysis of patients with narcolepsy to explore a potential biomarker which may help in diagnosis and further understanding of other possible etiological contribution of narcolepsy. This is a cross-sectional study conducted in the university-affiliated sleep clinic, and the study was approved by the Institutional Ethics Committee. In this study, 35 patients with narcolepsy were recruited (Table 1). Among all, 18 of them (51%) had cataplexy (NC). The diagnosis of narcolepsy was made according to the clinical and polysomnographic criteria as listed in the ICSD-2 [4]. Among all patients with narcolepsy, 26 of them completed HLA DQB1*0602 typing. Patients with idiopathic hypersomnia, IH, (N = 3) and other sleep disorders (include obstructive sleep apnea syndrome, N = 35, and parasomnia, N = 11) were also recruited. All these subjects underwent overnight PSG and MSLT, and completed the Epworth sleepiness scale (ESS). Healthy controls (N = 35) were recruited from the community, they underwent clinical interviews by sleep specialists to screen out sleep, physical, and psychiatric disorders. Albumin and IgG-depleted serum with ProteoPrep Blue Albumin and IgG Depletion kit (Sigma-Aldrich, St. Louis, MO, USA) was analyzed by Agilent 1100 high-performance liquid chromatography (HPLC) system with Diode Array (DAD) (California City, CA, USA) with Zorbax 300SB-C18 Analytical HPLC Column (2.1 mm ID 9 300 mm) at 30°C with flow rate at 0.3 mL/min based on the gradient elution with eluent A containing 0.01% trifluoroacetic acid (TFA) in water starting at 5–32% B in 40 min and to complete the elution with 90% B. The sample peak fractions at 20 min were collected for mass spectrometry. The novel serum protein fraction from the same patient with the same retention time from the HPLC analysis was pooled and analyzed using a MALDI-TOF/TOF tandem mass spectrometer ABI 4700 proteomics analyzer (Foster City, CA, USA) according to the manufacturer’s protocols. All mass spectrometry (MS) survey scan were acquired over the mass range 839–4013 m/z in the reflectron positive-ion mode and accumulated from 2000 laser shots with acceleration of 20 kV. The MS peaks (MH) were detected on minimum S/N ratio ≥ 20 and cluster area S/N threshold ≥ 25 without smoothing and raw spectrum filtering. The protein fraction of the same individual was subject to SDSPAGE onMini-PROTEAN II cell from BioRad according to manufacturer protocol. The gel was then stained with ProteoSilverTM Plus Silver Stain kit from Sigma Chemicals (St. Louis, MO, USA). A distinct protein peak fraction at 20 min (Figure 1) was detected more commonly (P < 0.01) among patients with narcolepsy (65.7%) when compared with patients with IH (0%), other sleep disorders (15.2%), and healthy controls (16.2%). This protein peak could be found in both NC (N = 18, 72%) and narcolepsy without cataplexy (N = 5, 50%) patients. In addition, the presence of peak B was found to have a moderate to high psychometric properties in discriminating narcolepsy from other sleep