An interesting case of late age at onset of narcolepsy with cataplexy.

The usual age at onset of narcolepsy with cataplexy is in the second or third decade. In cases with late onset narcolepsy with cataplexy, symptoms are usually mild with relatively less severe daytime sleepiness and less frequent cataplexy. Here we present a case of narcolepsy with cataplexy with onset of symptoms around sixty years of age. This case is unique, with severe daytime sleepiness both by subjective report as well as on objective Multiple Sleep Latency Test and having multiple cataplexy episodes in a day.

CPAP-induced mania in bipolar disorder: a case report.

OBJECTIVE: In this case report we present our clinical observations of two patients with bipolar disorder with comorbid obstructive sleep apnea (OSA) who were treated with continuous positive airway pressure (CPAP) for their sleep apnea. BACKGROUND: Bipolar disorder is a psychiatric disorder characterized by the presence of one or more episodes of mania and frequent episodes of depression. This disorder affects approximately 0.8% of the adult population, with estimates from community samples ranging between 0.4% and 1.6%. OSA syndrome is a severe sleep disorder with a prevalence of 2-4% in the general population, the risk of which is increased by obesity. The prevalence of OSA is expected to be high in bipolar disorder due to high comorbid obesity. It is expected that improvement in OSA in patients with bipolar disorder with CPAP will improve mood and other symptoms of bipolar disorder. However, there is a relative lack of data examining this aspect. RESULTS: In both cases of bipolar disorder, CPAP was started after a polysomnographic diagnosis of OSA and CPAP titration study indicating that most of the apneas/hypopneas were eliminated with a significant improvement in oxygen saturation. To our surprise, we noted that in both of these cases initiation of CPAP resulted in manic symptoms. CONCLUSIONS: Clinicians need to monitor patients with bipolar disorder closely for worsening of manic symptoms when they are started on CPAP for underlying OSA.

Subjective and objective sleep and self-harm behaviors in young children: a general population study.

Significant association between sleep disturbances and suicidal ideation and/or attempts is reported in adults and adolescents. However, there is paucity of studies exploring the association between sleep and self-harm behaviors (SHB) in young children and are limited to only subjective sleep measures. We examined the association between SHB and both subjective and objective sleep in a population-based sample of 5-12 yr old. Parents of every student in 3 local school (K-5) districts (n=7312) was sent a screening questionnaire. Randomly selected children from this sample underwent a comprehensive history, physical examination, a 9-h overnight polysomnogram and completed several questionnaires. Among the final sample (n=693), 27 children had SHB with adjusted prevalence of 3%. There was no difference in age, gender, obesity, or socioeconomic status in subjects with or without SHB. Significantly more children with SHB had subjective sleep difficulty and depression. Difficulty maintaining sleep and frequent nightmares were associated with SHB independent of depression or demographics. Polysomnographic %REM-sleep was significantly higher in the SHB group after adjusting for demographics and depression. These data indicate that parent reported sleep disturbances are independently associated with SHB. It is possible that higher REM-sleep is a non-invasive biomarker for risk of self-harm behaviors in young children.

Severe onychophagia and finger mutilation associated with obstructive sleep apnea.

Untreated obstructive sleep apnea (OSA) can lead to important neurobehavioral consequences including cognitive deficits, hyperactivity/inattention, daytime sleepiness, and mood disturbances. Interestingly, the potential role of OSA in the pathogenesis of impulse-control disorders such as nail biting (onychophagia) is currently unknown. We present a case of a man with severe onychophagia and biting-induced finger mutilation that was completely resolved after diagnosis and treatment of severe OSA. Accordingly, this report represents an important clinical observation that suggests a connection between sleep physiology and the neurobiological circuits implicated in the regulation of impulse-control behaviors. Further research in this area may improve our current understanding of the neurobehavioral consequences of untreated OSA.

Clinical and polysomnographic predictors of the natural history of poor sleep in the general population.

STUDY OBJECTIVES: Approximately 8-10% of the general population suffers from chronic insomnia, whereas another 20-30% of the population has insomnia symptoms at any given time (i.e., poor sleep). However, few longitudinal studies have examined risk factors of the natural history of poor sleep, and none have examined the role of polysomnographic (PSG) variables. DESIGN: Representative longitudinal study. SETTING: Sleep laboratory. PARTICIPANTS: From a random, general population sample of 1,741 individuals of the adult Penn State Cohort, 1,395 were followed up after 7.5 yr. MEASUREMENTS: Full medical evaluation and 1-night PSG at baseline and telephone interview at follow-up. RESULTS: The rate of incident poor sleep was 18.4%. Physical (e.g., obesity, sleep apnea, and ulcer) and mental (e.g., depression) health conditions and behavioral factors (e.g., smoking and alcohol consumption) increased the odds of incident poor sleep as compared to normal sleep. The rates of persistent, remitted, and poor sleepers who developed chronic insomnia were 39%, 44%, and 17%, respectively. Risk factors for persistent poor sleep were physical health conditions combined with psychologic distress. Shorter objective sleep duration and a family history of sleep problems were risk factors for poor sleep evolving into chronic insomnia. CONCLUSIONS: Poor sleep appears to be primarily a symptom of physical and mental health conditions, whereas the persistence of poor sleep is associated with psychologic distress. Importantly, sleep apnea appears to be associated with incident poor sleep but not with chronic insomnia. Finally, this study suggests that objective short sleep duration in poor sleepers is a biologic marker of genetic predisposition to chronic insomnia.

Risk factors for incident chronic insomnia: a general population prospective study.

OBJECTIVE: The few population-based, prospective studies that have examined risk factors of incident insomnia were limited by small sample size, short follow-up, and lack of data on medical disorders or polysomnography. We prospectively examined the associations between demographics, behavioral factors, psychiatric and medical disorders, and polysomnography with incident chronic insomnia. METHODS: From a random, general population sample of 1741 individuals of the adult Penn State Sleep Cohort, 1395 were followed-up after 7.5 years. Only subjects without chronic insomnia at baseline (n = 1246) were included in this study. Structured medical and psychiatric history, personality testing, and 8-h polysomnography were obtained at baseline. Structured sleep history was obtained at baseline and follow-up. RESULTS: Incidence of chronic insomnia was 9.3%, with a higher incidence in women (12.9%) than in men (6.2%). Younger age (20-35 years), non-white ethnicity, and obesity increased the risk of chronic insomnia. Poor sleep and mental health were stronger predictors of incident chronic insomnia compared to physical health. Higher scores in MMPI-2, indicating maladaptive personality traits, and excessive use of coffee at baseline predicted incident chronic insomnia. Polysomnographic variables, such as short sleep duration or sleep apnea, did not predict incident chronic insomnia. CONCLUSION: Mental health, poor sleep, and obesity, but not sleep apnea, are significant risk factors for incident chronic insomnia. Focusing on these more vulnerable groups and addressing the modifiable risk factors may help reduce the incident of chronic insomnia, a common and chronic sleep disorder associated with significant medical and psychiatric morbidity and mortality.

Persistent insomnia: the role of objective short sleep duration and mental health.

STUDY OBJECTIVES: Few population-based, longitudinal studies have examined risk factors for persistent insomnia, and the results are inconsistent. Furthermore, none of these studies have examined the role of polysomnographic (PSG) variables such as sleep duration or sleep apnea on the persistence of insomnia. DESIGN: Representative longitudinal study. SETTING: Sleep laboratory. PARTICIPANTS: From a random, general population sample of 1741 individuals of the adult Penn State Cohort, 1395 were followed-up after 7.5 years. MEASUREMENTS: Individuals underwent one-night PSG and full medical evaluation at baseline and a telephone interview at follow-up. PSG sleep duration was analyzed as a continuous variable and as a categorical variable: < 6 h sleep (short sleep duration) and ≥ 6 h sleep (longer sleep duration). RESULTS: The rates of insomnia persistence, partial remission, and full remission were 44.0%, 30.0%, and 26.0%, respectively. Objective short sleep duration significantly increased the odds of persistent insomnia as compared to normal sleep (OR = 3.19) and to fully remitted insomnia (OR = 4.92). Mental health problems at baseline were strongly associated with persistent insomnia as compared to normal sleep (OR = 9.67) and to a lesser degree compared to fully remitted insomnia (OR = 3.68). Smoking, caffeine, and alcohol consumption and sleep apnea did not predict persistent insomnia. CONCLUSIONS: Objective short sleep duration and mental health problems are the strongest predictors of persistent insomnia. These data further support the validity and clinical utility of objective short sleep duration as a novel marker of the biological severity of insomnia.

A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

BACKGROUND AND RATIONALE: Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear whether the same acute effects occur in humans. METHODOLOGY/PRINCIPAL FINDINGS: A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8) and female (7) subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC) by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203) and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170), whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166) and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184), respectively after olanzapine. Other measures were unchanged. CONCLUSIONS/SIGNIFICANCE: Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics. TRIAL REGISTRATION: ClinicalTrials.gov NCT00741026.

Nocturnal sleep panic and depression: relationship to subjective sleep in panic disorder.

BACKGROUND: Patients with panic disorder (PD) often complain of sleep disturbances. PD patients have high co-morbid depression and almost 65-70% reports a history of nocturnal panic attacks. It is possible that both nocturnal-sleep panic attacks and depression contribute to sleep disturbances in PD patients. However, the individual and interactive effects of nocturnal-sleep panic attacks and lifetime depression on subjective sleep in PD are unknown. METHODS: The National Institute of Mental Health Panic Disorder Questionnaire (NIMH-PQ) was administered to 773 individuals who met DSM-IV criteria for PD. All of these subjects completed queries related to nocturnal-sleep panic attacks, lifetime depression, difficulty sleeping, and sleep duration. RESULTS: We examined difficulty in sleeping and sleep duration in four subgroups [PD without nocturnal panic attacks or lifetime depression (NP-D-), PD with nocturnal panic attacks (NP+D-), PD with lifetime depression (NP-D+), and PD with both nocturnal panic attacks and lifetime depression (NP+D+)]. Significantly greater proportions of NP+D+ subjects reported difficulty sleeping compared to other three subgroups. In addition, the NP+D+ patients reported significantly decreased subjective sleep durations compared to the other three subgroups. Using < or = 5h as a criteria for severe sleep restriction, approximately 20% of the NP+D+ patients, compared to 9.2%, 9.6%, and 2.5% in the NP+D-, NP-D+, NP-D- subgroups, respectively, reported sleeping 5h or less. 8.2% of panic disorder patients reported excessive sleeping per sleeping period. CONCLUSIONS: A high percentage of panic disorder individuals report subjective sleep disturbances. Not surprisingly, an unusually high prevalence of patients with nocturnal panic attacks or depression have sleep problems and 92.3% of patients with both nocturnal panic attacks and depression report striking extremes in sleep duration or insomnia. Thus, nocturnal-sleep panic attacks and depression are independently as well as interactively associated with increased sleep disturbances in panic disorder. Although these findings are expected, they underscore the importance of assessing sleep functions, including over-sleeping, in panic disorder patients.

Medical complaints are more common in young school-aged children with parent reported insomnia symptoms.

OBJECTIVE: Studies in adults have found significant association between sleep disturbances and various medical symptoms/disorders. However, in children, few studies have explored this complex association in clinical samples. In this study, we examined prevalence of medical complaints in children with insomnia symptoms in a large general population of school aged children. METHODS: We conducted a cross sectional study of 700 children, ages 5-12 years, from the Penn State Children's Cohort. All children underwent a medical and psychiatric history, physical examination, 9-h overnight polysomnography, and neuropsychological testing. Comprehensive sleep and development questionnaires were completed by a parent. We compared 135 (19.3%) children with parent-reported sleep disturbances to 565 (80.7%) children with no parent-reported sleep disturbances. RESULTS: Insomnia symptoms were significantly associated with gastrointestinal regurgitation and headaches after controlling for demographic variables, apnea hypopnea index, ADHD, learning disorder or other psychiatric/behavioral disorder, socioeconomic status, and minority status. Children with gastrointestinal regurgitation and headaches compared to children without these symptoms were 3.3 times and 2.3 times as likely to suffer from sleep disturbances, respectively. Objectively, sleep latency increased in the sleep disturbance group, and there were significant differences between groups in REM latency, slow wave, and stage 2 sleep. DISCUSSION: These results underscore the importance of inquiring about insomnia symptoms when children present with medical complaints particularly gastrointestinal regurgitation or headaches and taking a comprehensive medical history when children present with sleep complaints. Future studies are needed to replicate these findings and explore the possible underlying pathophysiological abnormalities of such comorbidity between insomnia symptoms and medical symptoms in children.

Role of acupuncture in the treatment of insomnia: a comprehensive review.

Insomnia is a common sleep disorder with devastating socioeconomic consequences. Even though there are pharmacological and behavioral treatments for insomnia, most of the patients are treated with medications. However, the long-term use of medications to treat insomnia is questioned and has potential side effects. More and more Americans are seeking complementary/alternative treatments for many conditions including insomnia and there are anecdotal reports/case series of use of acupuncture in treating insomnia. To examine critically the role of acupuncture in treatment of insomnia, we performed a systematic review of published literature. Among the selected studies for review many were clinical case series and few open or randomized clinical trails. Even though several of these studies did not clarify the nature of insomnia (primary vs. secondary), it seemed that many of the subjects enrolled in these studies had co-morbid other psychiatric (depression or anxiety disorders) and/or medical conditions (Hemodialysis, Stroke, Pregnancy). Except for few, several of these studies had methodological limitations. Despite the limitations of the reviewed studies, all of them consistently indicate significant improvement in insomnia with acupuncture. Further methodologically strong, randomized controlled studies with large sample size are needed to assess the usefulness of acupuncture in treatment of insomnia and explore the possible mechanisms underlying the effects of acupuncture on sleep and sleep disorders.

Differential effects of hypocretins on noise-alone versus potentiated startle responses.

Hypocretins are recently discovered neuropeptides, synthesized exclusively in the hypothalamus with excitatory efferents to noradrenergic, serotonergic, and GABAergic (gamma-aminobutyric acid) neurons. Hypocretins also increase corticotropin releasing hormone (CRH) secretion. These actions suggest a possible role for hypocretins in the neurobiology of anxiety, fear, or startle mechanisms. We examined the effects of intracerebroventricular (ICV) administration of hypocretin-A and hypocretin-B on behavior in the Startle Potentiated Startle (SPS) paradigm, a repeated measures, non-shock animal model for studying the classically conditioned enhancement of acoustic startle in the rat. SPS has been used to study effects of anxiolytic treatments. Male Sprague-Dawley rats were tested using the SPS paradigm for 3 days (M-W-F). Following training, rats were anesthetized and 26 gauge stainless cannulae were permanently implanted into the lateral ventricle for intracerebroventricular (ICV) infusions. Following 6-9 days of recovery period, the M-W-F SPS testing was resumed. ICV infusion of both Hypocretin-A (1 and 3 nM) and Hypocretin-B (3 and 10 nM) produced significant reduction in Noise Alone Startle amplitude compared to pre-infusion baseline, whereas infusion with vehicle did not affect Noise Alone Startle. The effect of Hypocretin-B was brief (first 10 min post-infusion), whereas the effect of Hypocretin-A persisted across much of the 50 min post-infusion period. Neither Hypocretin-A nor Hypocretin-B significantly altered the magnitude of the SPS response. Contrary to our expectations, hypocretins seems to possess anxiolytic rather than pro-anxiogenic properties, as indicated by decrease in Noise Alone Startle.

Skin picking and sleep disturbances: relationship to anxiety and need for research.

Pathological excoriation (PE) or skin picking is seen in nearly 2% of patients attending dermatology clinics and is often associated with anxiety, stress and frequent help-seeking behaviors. While anxiety and stress are thought to cause poor sleep in the general population, not all anxious people, even those with disabling anxiety disorders, necessarily suffer from insomnia or other sleep problems. The relationship between anxiety symptoms and poor sleep, therefore, remains unclear and sleep quality in PE is unknown. We examined the sleep quality and levels of anxiety in dermatological patients with PE. Dermatological patients with (n = 10) and without (n = 10) PE and healthy controls (n = 10) were assessed on standardized and validated measures of subjective sleep quality [Pittsburgh Sleep Quality Index (PSQI)], anxiety (Spielberger State and Trait Anxiety Inventory; modified Zung Anxiety Scale), stress (Perceived Stress Scale) and work and social disability [Sheehan Disability Inventory subscale (SDI-4)]. Patients with dermatological complaints as a group reported poorer sleep quality, higher scores on Spielberger State and Zung anxiety, perceived stress, and SDI-4. Among both groups of dermatological patients, only the PE group had significantly poor sleep, high anxiety, and perceived stress compared to healthy controls. In the dermatological patients with PE, PSQI-global scores were significantly positively correlated to Spielberger State and Zung Anxiety scores. Dermatological patients with PE are more anxious and have poorer subjective sleep compared to dermatological patients without PE and healthy. Future research is needed to elucidate these relationship factors and to develop new behavioral and drug treatments for the management of PE.

Long-term therapy with lithium in a private practice clinic: a naturalistic study.

OBJECTIVE: To document the effectiveness and vicissitudes of treating 14 bipolar patients with lithium carbonate over a combined 300 years, and an average of 21 years/patient. METHODS: Chart review of the narrative and laboratory studies of these 14 patients ranging in duration from 12 to 29 years. RESULTS: Lithium stabilized these bipolar patients over these periods. Only three patients required hospitalization, one because lithium was slowly tapered at her request after 6 years of mood stability, another because of non-compliance, and a third because of co-morbid alcohol abuse. One patient attempted suicide after lithium was tapered off. However, in some patients, there were serious side-effects necessitating lithium discontinuation. CONCLUSIONS: Controlled studies in psychopharmacology are obviously preferred to open-label or naturalistic case studies. However, controlled studies are rarely conducted over long periods, and practice-related naturalistic research can be of value, albeit anecdotal and without the use of structured rating scales. In this paper, we are reporting on 14 patients seen consistently by one psychiatrist. These patients were functional and productive at work and in family life. The patients suffered brief hypomanic or depressive episodes. Although several patients experienced serious side-effects, lithium was continued with stable mood, while the side-effects were managed in collaboration with other specialists.

Sleep in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is often associated with sleep disturbances. In this review, we focus on the published literature on subjective and objective findings of sleep in patients with PTSD. Insomnia and nightmares are most commonly reported subjective sleep disturbances. Polysomnographic investigations have frequently reported rapid eye movement (REM) sleep abnormalities in PTSD. However, studies have not been consistent about the type of REM sleep dysfunction in PTSD patients. Antidepressants such as nefazodone, trazodone, fluvoxamine, and imagery rehearsal therapy are found to be beneficial in the treatment of PTSD associated sleep disturbances as well as core symptoms of this anxiety disorder. We propose use of such modalities of treatment in PTSD patients with predominant sleep disturbances. Further studies are required to clarify polysomnographic sleep changes especially role of REM sleep dysregulation and treatment of sleep disturbances in PTSD.