Genetic variants in RBFOX3 are associated with sleep latency.

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.

[A homeless, uninsured illegal alien suffering from psychosis and multiple fractures: providing efficient care to such patients]. / Een dakloze, onverzekerde illegaal met multipele fracturen en een psychose: Hoe kun je zo'n patiënt doelmatige zorg verlenen?

We present the case of a 37-year-old psychotic, homeless man from Albania, who sustained multiple fractures after jumping from a third-floor window. The patient was uninsured and did not consent to transfer to a hospital in Albania because of paranoid delusions. Eventually he was hospitalised for nearly 30 weeks in hospital and a nursing home. Various factors of this complex case are considered, such as the co-morbidity of somatic and psychiatric symptoms, the absence of family support and the financial regulations that apply to uninsured patients. Doctors who are presented with similar complex cases are advised to organise frequent multidisciplinary evaluations with all health care workers involved. We encourage searching for creative interventions which serve both the best interests of the individual patient, and - where possible - also minimize the total cost of health care to society.

Sleep duration, but not insomnia, predicts the 2-year course of depressive and anxiety disorders.

OBJECTIVE: To examine the predictive role of insomnia and sleep duration on the 2-year course of depressive and anxiety disorders. METHOD: This study is a secondary data analysis based on data from the baseline (2004-2007) and 2-year assessment of the Netherlands Study of Depression and Anxiety. Participants were 1,069 individuals with DSM-IV-based depressive and/or anxiety disorders at baseline. Sleep measures included insomnia (Women's Health Initiative Insomnia Rating Scale score ≥ 9) and sleep duration (categorized as short [≤ 6 hours], normal [7-9 hours], or long [≥ 10 hours]). Outcome measures were persistence of DSM-IV depressive and anxiety disorders (current diagnosis at 2-year follow-up), time to remission, and clinical course trajectory of symptoms (early sustained remission, late remission/recurrence, and chronic course). Logistic regression analyses were adjusted for sociodemographic characteristics and chronic medical disorders, psychotropic medications, and severity of depressive and anxiety symptoms. RESULTS: The effect of insomnia on persistence of depressive and/or anxiety disorders (OR = 1.50; 95% CI, 1.16-1.94) was explained by severity of baseline depressive/anxiety symptoms (adjusted OR with severity = 1.04; 95% CI, 0.79-1.37). Long sleep duration was independently associated with persistence of depression/anxiety even after adjusting for severity of psychiatric symptoms (OR = 2.52; 95% CI, 1.27-4.99). For short sleep duration, the independent association with persistence of combined depression/anxiety showed a trend toward significance (OR = 1.32; 95% CI, 0.98-1.78), and a significant association for the persistence of depressive disorders (OR = 1.49; 95% CI, 1.11-2.00). Both short and long sleep duration were independently associated with a chronic course trajectory (short sleep: OR = 1.50; 95% CI, 1.04-2.16; long sleep: OR = 2.91, 95% CI, 1.22-6.93). DISCUSSION: Both short and long sleep duration-but not insomnia-are important predictors of a chronic course, independent of symptom severity. It is to be determined whether treating these sleep conditions results in more favorable outcomes of depression and anxiety.

Sleep disturbances and reduced work functioning in depressive or anxiety disorders.

OBJECTIVES: We aimed to examine the associations between sleep disturbances and work functioning in an epidemiologic cohort study in subjects with or without depressive or anxiety disorders. METHODS: There were 707 subjects included in our analyses with depressive or anxiety disorders and 728 subjects without current depressive or anxiety disorders. Insomnia was defined as a score ≥9 using the Insomnia Rating Scale. Self-reported sleep duration was categorized in short, normal, and long (≤6, 7-9, and ≥10 h, respectively). Work absenteeism was defined as none, short (≤2 weeks), or long (>2 weeks). Work performance was defined as not impaired, reduced, or impaired. Logistic regression analyses were performed to examine the associations of sleep disturbances with work functioning. RESULTS: In subjects with psychopathology, insomnia and short sleep duration were significantly associated with impaired work performance (odds ratio [OR] for insomnia, 2.20; [95% confidence interval {CI}, 1.50-3.22]; OR for short sleep, 2.54 [95% CI, 1.66-3.88] compared to normal sleep duration). Insomnia (OR, 2.48 [95% CI, 1.67-3.69]) and short sleep duration (OR, 1.85 [95% CI, 1.23-2.78]) also were associated with long-term absenteeism. These findings remained the same after considering clinical characteristics including medication use and symptom severity. In subjects without psychopathology, no significant associations were found between insomnia and short sleep duration on work functioning after considering subthreshold depression symptoms. CONCLUSIONS: In subjects with psychopathology, sleep disturbances were negatively associated with work functioning, independent of disorder severity and use of psychotropic medication. Further research is needed to determine if treatment of sleep disturbances in subjects with psychopathology improves work functioning.

Insomnia and sleep duration in a large cohort of patients with major depressive disorder and anxiety disorders.

OBJECTIVE: Disturbed sleep has a high impact on daily functioning and has been correlated with psychopathology. We investigated the extent to which insomnia and sleep duration were associated with both current and remitted depressive and anxiety disorders in a large-scale epidemiologic study, taking sociodemographics, health factors, and medication use into account. METHOD: Data of 2,619 individuals from the Netherlands Study of Depression and Anxiety (NESDA) were analyzed. Psychopathology was classified as no, current, or remitted DSM-IV-based diagnosis of major depressive or anxiety disorder. Outcome measures were insomnia (Women's Health Initiative Insomnia Rating Scale score >or= 9) and sleep duration (or= 10 hours). Baseline measurement was conducted between September 2004 and February 2007. RESULTS: Both current and remitted depressive disorder and current anxiety disorder were associated with insomnia and short sleep duration with odds ratios (ORs) for insomnia ranging from 1.42 to 3.23 and for short sleep duration ranging from 1.41 to 2.53. Associations were stronger for current than for remitted diagnoses and stronger for depressive than for anxiety disorders. Also long sleep duration was associated with current depressive disorder and anxiety disorders (OR range, 1.53-2.66). Sociodemographic factors, health indicators, and psychotropic medication use did contribute to sleep outcomes but could not explain much of the psychopathology and sleep associations. CONCLUSION: Depressive disorder-but also anxiety disorder-is strongly associated with sleep disturbances. Insomnia and short sleep duration persist after remittance of these disorders, suggesting that these are residual symptoms or possibly trait markers. Also, long sleep duration is associated with current depressive or anxiety disorders.