C-L Case Conference: Insomnia Disorder.

We present the case of a 67-year-old male with a history of major depressive disorder, panic disorder, treatment refractory hypertension, dyslipidemia, benign prostatic hypertrophy, and environmental allergies who was initially brought to medical attention following an unwitnessed fall. He subsequently developed symptoms of insomnia disorder. Experts in consultation-liaison psychiatry and sleep medicine provide guidance for this clinical scenario based on their experience and a review of current literature, exploring the epidemiology of insomnia disorder and comorbidities in relation to this case. Furthermore, we offer a review of current treatment for insomnia disorder, including non-pharmacologic methods such as cognitive behavioral therapy for insomnia and pharmacotherapy.

Aripiprazole, a Novel Option in the Management of Restless Legs Syndrome (RLS) Patients with Augmentation and/or Severe RLS Symptoms: A Report of 4 Cases.

Purpose: Restless Legs Syndrome (RLS) is a sensorimotor disorder associated with an unpleasant urge to move the limbs, relieved with movement, occurring in the evenings and with prolonged rest/inactivity. Treatment with dopamine agonists is effective for up to 60-90% of affected individuals. However, augmentation, ie, the paradoxical worsening of RLS symptoms after prolonged RLS treatment, is frequently reported, typically after 3-10 years of treatment. Here, we present 4 patients with RLS who were successfully treated with dopamine agonists but later developed augmentation. A trial of aripiprazole, a dopamine receptor partial agonist (DRPA), was initiated for treatment of augmentation symptoms. Patients and Methods: Four patients treated for RLS with dopamine agonists developed augmentation. In each instance, augmentation symptoms did not respond adequately to a variety of medications including α2δ drugs, opioids or other agents. A trial of aripiprazole was initiated for each patient, and effects were evaluated. Results: All four patients with severe RLS and augmentation with dopamine agonists achieved symptom control with aripiprazole. Patients endorsed 90-100% efficacy with aripiprazole by subjective self-report after failures with other agents. Further evaluation with the International Restless Legs Syndrome Study Group RLS Rating Scale (IRLS-SGRS) showed that benefits (from moderate to very severe, to mild to moderate severity) were largely maintained for 1-2 years. Aripiprazole doses to control augmentation symptoms were low (1-4 mg). No significant side effects were reported. Conclusion: Aripiprazole may have utility for augmentation in RLS. We speculate that the partial agonist and antagonist properties of aripiprazole may limit potential for dopamine hyposensitization to progress to cause augmentation. Further research is needed to see if aripiprazole and/or other DRPAs are a viable long-term treatment option for patients experiencing augmentation and/or severe RLS with dopamine agonist therapy.

Vestibular symptoms are related to the proportion of REM sleep in people with sleep complaints: A preliminary report.

OBJECTIVE/BACKGROUND: Though sleep problems (apnea, insomnia) and related daytime symptoms (fatigue, anxiety, depression) have been associated with vestibular problems (falls, dizziness), it is not well known which particular sleep features relate to vestibular problems. We thus assessed symptoms of vestibular problems in patients visiting a sleep clinic and evaluated how they were associated with objective sleep parameters derived from polysomnography and relevant daytime symptoms. PATIENTS/METHODS: The polysomnography data of thirty-one patients (61% female, between 20 and 79 years of age) who were referred for clinical sleep assessment was collated with subjective measures of symptoms linked to vestibular problems (rated on the Situational Characteristics Questionnaire), as well as fatigue, anxiety and depression symptoms. Multiple linear regression was used to identify factors associated with vestibular symptoms, including analyses adjusted for age, sex, medication use and total sleep time. RESULTS: A higher percentage of REM sleep and more severe anxiety symptoms were independently associated with more severe vestibular symptoms, which survived adjusted analyses. Other sleep stages, as well as as sleep efficiency, apnea-hypopnea index and oxygen saturation were not significantly related to vestibular symptoms. CONCLUSIONS: These results point at vestibular symptoms as possible important and overlooked correlates of variations in sleep architecture in individuals with sleep complaints. Though replication is needed to confirm findings from this limited sample, the results highlight the importance of assessing vestibular symptoms in people with sleep complaints. In particular, further investigations will need to address the potential implication of REM sleep for vestibular functions and the directionality of this relation.

A week long "pep" talk - initial and 2-3-year longitudinal data on the Ottawa Psychiatry Enrichment Program (OPEP).

BACKGROUND: Recruitment to psychiatry as a career has been challenging in Canada and abroad despite the known shortage and increasing burden of psychiatric issues globally. Deterrents to choosing psychiatry as a career include its negative stigma and paucity of knowledge about the field. The study goal was to evaluate the Ottawa Psychiatry Enrichment Program (OPEP), a one-week extracurricular program about psychiatry as a career for 1st and 2nd year medical students. We hypothesized OPEP would improve students' attitudes towards psychiatry, and positive changes would be sustained 2-3 years later following their residency match. We hypothesized there would be a high recruitment of OPEP attendees to psychiatry programs. METHODS: 1st and 2nd year medical students from Canada applied to OPEP. Attendees completed the Attitudes Towards Psychiatry Questionnaire (ATP-30) at three times: before OPEP (PreOPEP), after OPEP (PostOPEP) and after their Canadian Residency Matching Service (CaRMs) match 2-3 years later. OPEP ATP-30 scores were compared to third-year student ATP-30 scores before and after their psychiatry rotation. Data were analysed using Friedman non-parametric ANOVA and post hoc testing by either Wilcoxon rank sum test, Wilcoxon matched pairs signed rank test, or parametric Welch independent t-test as appropriate. Effect sizes of group mean differences were calculated using Cohen's "d". RESULTS: Between 2017-2018, 29/53 Canadian applicants were selected for OPEP. 100%, 93.1% and 75.8% of OPEP students completed the PreOPEP, PostOPEP, and CaRMs ATP-30 surveys respectively. 43% of OPEP attendees matched to psychiatry. PostOPEP ATP-30 scores (mean = 133, median = 137, SD = 10.6) were significantly higher than PreOPEP ATP-30 (mean score = 121, median = 122, SD = 9.3, p < 0.001) and CaRMS ATP-30 (mean = 126, median = 127, SD = 12.3, p < 0.02) scores. OPEP effect size on ATP-30 scores was large (d = 1.2) but decreased 2-3 years later (p = 0.078, d = 0.44). 97/202 students completed the ATP-30 before and after their psychiatry rotation (clerkship). Clerkship effect size on improvement in ATP-30 was moderate (d = 0.39). There was a non-significant difference between OPEP CaRMS ATP-30 and post clerkship ATP-30 scores (median 127 vs 121, p = 0.056). CONCLUSIONS: OPEP ameliorated attitudes toward Psychiatry, but improvement deteriorated longitudinally. Strategies for program design, and innovations to boost/retain improvements during clerkship years are discussed.

Selective serotonin reuptake inhibitor use is associated with worse sleep-related breathing disturbances in individuals with depressive disorders and sleep complaints: a retrospective study.

STUDY OBJECTIVES: The effects of serotonergic agents on respiration neuromodulation may vary according to differences in the serotonin system, such as those linked to depression. This study investigated how sleep-related respiratory disturbances relate to depression and the use of medications commonly prescribed for depression. METHODS: Retrospective polysomnography was collated for all 363 individuals who met selection criteria out of 2,528 consecutive individuals referred to a specialized sleep clinic (Ottawa, Canada) between 2006 and 2016. The apnea-hypopnea index (AHI), oxygen saturation nadir, and oxygen desaturation index during REM and NREM sleep were analyzed using mixed analyses of covariance comparing 3 main groups: (1) medicated individuals with depressive disorders (antidepressant group; subdivided into the selective serotonin reuptake inhibitor and norepinephrine-dopamine reuptake inhibitor subgroups), (2) non-medicated individuals with depressive disorders (non-medicated group), and (3) mentally healthy control patients (control group). RESULTS: Individuals with depressive disorders (on antidepressants or not) had significantly higher AHIs compared to control patients (both P ≤ .007). The antidepressant group had a lower NREM sleep oxygen saturation nadir and a higher NREM sleep oxygen desaturation index than the control and non-medicated groups (all P ≤ .009). Within individuals with depressive disorders, independent of depression severity, the selective serotonin reuptake inhibitor group had a lower oxygen saturation nadir and a higher oxygen desaturation index during NREM sleep than the norepinephrine-dopamine reuptake inhibitor (both P ≤ .045) and non-medicated groups (both P < .001) and a higher NREM sleep AHI than the non-medicated group (P = .014). CONCLUSIONS: These findings suggest that the use of selective serotonin reuptake inhibitors may be associated with impaired breathing and worse nocturnal oxygen saturation in individuals with depressive disorders and sleep complaints, but this needs to be confirmed by prospective studies.

Profiles of sleep changes during the COVID-19 pandemic: Demographic, behavioural and psychological factors.

This study aimed to evaluate changes in sleep during the COVID-19 outbreak, and used data-driven approaches to identify distinct profiles of changes in sleep-related behaviours. Demographic, behavioural and psychological factors associated with sleep changes were also investigated. An online population survey assessing sleep and mental health was distributed between 3 April and 24 June 2020. Retrospective questions were used to estimate temporal changes from before to during the outbreak. In 5,525 Canadian respondents (67.1% females, 16-95 years old: Mean ± SD = 55.6 ± 16.3 years), wake-up times were significantly delayed relative to pre-outbreak estimates (p < .001, ηp2  = 0.04). Occurrences of clinically meaningful sleep difficulties significantly increased from 36.0% before the outbreak to 50.5% during the outbreak (all p < .001, g ≥ 0.27). Three subgroups with distinct profiles of changes in sleep behaviours were identified: "Reduced Time in Bed", "Delayed Sleep" and "Extended Time in Bed". The "Reduced Time in Bed" and "Delayed Sleep" subgroups had more adverse sleep outcomes and psychological changes during the outbreak. The emergence of new sleep difficulties was independently associated with female sex, chronic illnesses, being employed, family responsibilities, earlier wake-up times, higher stress levels, as well as heavier alcohol use and television exposure. The heterogeneity of sleep changes in response to the pandemic highlights the need for tailored interventions to address sleep problems.

Autonomic Modulation of Cardiac Activity Across Levels of Sleep Depth in Individuals With Depression and Sleep Complaints.

OBJECTIVE: We assessed mean heart rate (HR) and HR variability (HRV) across wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep, and across varying levels of NREM sleep depth in individuals with depression and sleep complaints. METHODS: Retrospective polysomnographic data were obtained for 25 individuals diagnosed as having depression (84% female; mean age = 33.8 ± 12.2 years) and 31 mentally healthy controls (58.1% female; mean age = 37.2 ± 12.4 years). All were free of psychotropic and cardiovascular medication, cardiovascular disease, and sleep-related breathing disorders. HR and time-domain HRV parameters were computed on 30-second electrocardiography segments and averaged across the night for each stage of sleep and wake. RESULTS: Compared with the control group, the depression group had higher HR across wake, REM, and all levels of NREM depth (F(1,51) = 6.3, p = .015). Significant group by sleep stage interactions were found for HRV parameters: SD of normal-to-normal intervals (SDNN; F(2.1,107.7) = 4.4, p = .014) and root mean square differences of successive R-R intervals (RMSSD; F(2.2,113.5) = 3.2, p = .041). No significant group difference was found for SDNN or RMSSD during wake (all, p ≥ .32). However, compared with the control group, the depression group had significantly lower SDNN in REM (p = .040) and all NREM stages (all p ≤ .045), and lower RMSSD during NREM 2 (p = .033) and NREM 3 (p = .034). CONCLUSIONS: This study suggests that the abnormalities in autonomic cardiac regulation associated with depression and sleep problems are more prominent during sleep, especially NREM sleep, than during wake. This may be due to abnormalities in parasympathetic modulation of cardiac activity.

Using heart rate profiles during sleep as a biomarker of depression.

BACKGROUND: Abnormalities in heart rate during sleep linked to impaired neuro-cardiac modulation may provide new information about physiological sleep signatures of depression. This study assessed the validity of an algorithm using patterns of heart rate changes during sleep to discriminate between individuals with depression and healthy controls. METHODS: A heart rate profiling algorithm was modeled using machine-learning based on 1203 polysomnograms from individuals with depression referred to a sleep clinic for the assessment of sleep abnormalities, including insomnia, excessive daytime fatigue, and sleep-related breathing disturbances (n = 664) and mentally healthy controls (n = 529). The final algorithm was tested on a distinct sample (n = 174) to categorize each individual as depressed or not depressed. The resulting categorizations were compared to medical record diagnoses. RESULTS: The algorithm had an overall classification accuracy of 79.9% [sensitivity: 82.8, 95% CI (0.73-0.89), specificity: 77.0, 95% CI (0.67-0.85)]. The algorithm remained highly sensitive across subgroups stratified by age, sex, depression severity, comorbid psychiatric illness, cardiovascular disease, and smoking status. CONCLUSIONS: Sleep-derived heart rate patterns could act as an objective biomarker of depression, at least when it co-occurs with sleep disturbances, and may serve as a complimentary objective diagnostic tool. These findings highlight the extent to which some autonomic functions are impaired in individuals with depression, which warrants further investigation about potential underlying mechanisms.

Geriatric Psychiatry Teaching in Canadian Medical Schools: a Cross-Sectional Study.

OBJECTIVE: With a growing geriatric population and limited geriatric psychiatrists in Canada, it is crucial to provide sufficient training in geriatric psychiatry during medical school. The authors examined how geriatric psychiatry education is delivered in Canadian medical schools during clerkship. Factors that could be associated with increased geriatric psychiatry teaching in medical schools were examined. The authors were also interested in comparing Canadian to US findings. METHODS: A cross-sectional survey was distributed to the psychiatry medical education representatives attending the Canadian Organization of Undergraduate Psychiatry Educators (COUPE) semi-annual meeting in September 2017. RESULTS: All 17 (100%) medical schools completed the survey. Fifteen of the 17 schools (88%) have geriatric psychiatry-specific learning objectives. Five schools (29%) offer a clinical component in geriatric psychiatry. One school has an award for clerks (6%), and no awards exist for faculty. The number of lecture hours in geriatric psychiatry is moderately correlated with the presence of a geriatric component to psychiatry clerkship (Spearman's rho = 0.67, p = 0.003) and the length of the geriatric portion of clerkship (Spearman's rho = 0.64, p value = 0.006). Lecture hours are also moderately correlated with the presence of a geriatric fellowship (Spearman's rho = 0.68, p value = 0.003). CONCLUSIONS: Geriatric psychiatry clerkship education is inconsistent in Canada. There is virtually no recognition of excellence in teaching or undergraduate performance in this area in clerkship. Geriatric psychiatry may receive more frequent attention in Canadian medical schools than in US medical schools.

Sleep-related breathing disturbances in adolescents with treatment resistant depression.

OBJECTIVE/BACKGROUND: A considerable subgroup of adolescents does not respond to standard antidepressant treatments. There are some indications that sleep disordered breathing may contribute to refractory depression in adults, but little is known about how it may relate to the course of depressive disorders in adolescents. Focussing on a group of Canadian adolescents with treatment resistant depression (TRD), this study aimed to investigate how the severity of residual depressive symptoms following unsuccessful antidepressant trials relates to breathing disturbances during sleep. PATIENTS/METHODS: A retrospective chart review was conducted at a tertiary mental health facility. Polysomnography, the Beck Depression Inventory-II (BDI-II), and the Epworth Sleepiness Scale (ESS) were collated from 18 adolescents (15-18 years old, 44% females) patients with depressive disorders who did not respond to at least two 4-week trials of antidepressant medications. RESULTS: Of this sample, 39% reported at least mild levels of excessive daytime sleepiness, and 55% had an apnea/hypopnea index ≥1. Worse depressive symptoms correlated with higher RDI (r = 0.53, p = 0.022). This was mainly driven by respiratory effort-related arousals occurring during NREM sleep (r = 0.52, p = 0.029). No significant correlation was found between depressive symptoms and other respiratory or sleep variables. Higher daytime sleepiness correlated significantly with lower minimum oxygen desaturation (r = -0.51, p = 0.030). CONCLUSIONS: These results suggest that even subtle respiratory disturbances during sleep may play a role in persistent depressive symptoms and treatment resistance. Early screening for sleep-related breathing disturbances in adolescents with TRD may be relevant, since previous work suggests that treating sleep-related breathing disturbances can attenuate depressive symptoms.

Rapid Evolution of Primate Type 2 Immune Response Factors Linked to Asthma Susceptibility.

Host immunity pathways evolve rapidly in response to antagonism by pathogens. Microbial infections can also trigger excessive inflammation that contributes to diverse autoimmune disorders including asthma, lupus, diabetes, and arthritis. Definitive links between immune system evolution and human autoimmune disease remain unclear. Here we provide evidence that several components of the type 2 immune response pathway have been subject to recurrent positive selection in the primate lineage. Notably, substitutions in the central immune regulator IL13 correspond to a polymorphism linked to asthma susceptibility in humans. We also find evidence of accelerated amino acid substitutions as well as gene gain and loss events among eosinophil granule proteins, which act as toxic antimicrobial effectors that promote asthma pathology by damaging airway tissues. These results support the hypothesis that evolutionary conflicts with pathogens promote tradeoffs for increasingly robust immune responses during animal evolution. Our findings are also consistent with the view that natural selection has contributed to the spread of autoimmune disease alleles in humans.

The State of Sleep Medicine Education in North American Psychiatry Residency Training Programs in 2013: Chief Resident's Perspective.

OBJECTIVE: To assess the current state of sleep medicine educational resources and training offered by North American psychiatry residency programs. METHODS: In June 2013, a 9-item peer-reviewed Sleep Medicine Training Survey was administered to 39 chief residents of psychiatry residency training programs during a meeting in New York. RESULTS: Thirty-four percent of the participating programs offered an elective rotation in sleep medicine. A variety of innovative approaches for teaching sleep medicine were noted. The majority of the chief residents felt comfortable screening patients for obstructive sleep apnea (72%), half felt comfortable screening for restless legs syndrome (53%), and fewer than half were comfortable screening for other sleep disorders (47%). CONCLUSIONS: This is the first report in the last decade to provide any analysis of current sleep medicine training in North American psychiatry residency training programs. These data indicate that sleep medicine education in psychiatry residency programs is possibly in decline.

Baclofen for narcolepsy with cataplexy: two cases.

Narcolepsy is a disabling sleep disorder characterized by daytime hypersomnolence. Those with cataplexy have spells of muscle weakness precipitated by strong emotions, especially laughter or surprise. Cataplexy treatments include antidepressants or a GABA-B agonist, gamma hydroxybutyrate (GHB). GHB is the most effective treatment for cataplexy, but is expensive and can have significant side effects. A recent report of a murine model of narcolepsy-cataplexy suggests R-baclofen has potential efficacy against cataplexy. We report on two narcolepsy patients with multiple daily cataplexy episodes, one of whom had been effectively treated with GHB, but had to discontinue it for unrelated medical reasons. Both subsequently tried baclofen and experienced almost complete resolution of cataplexy. This report suggests baclofen can be an effective treatment for cataplexy in humans and warrants further study.

Factors affecting recruitment into psychiatry: a canadian experience.

OBJECTIVE: There is a projected shortage of psychiatrists in Canada in forthcoming years. This study assessed factors in medical school education that are associated with students selecting psychiatry first and matching as a discipline. METHOD: The Canadian Organization of Undergraduate Psychiatry Educators (COUPE) conducted telephone interviews and sent e-mail questionnaires to the 17 medical schools across Canada; all schools provided data for 2012. Relevant data were obtained from the Canadian Resident Matching Service. Statistics were performed using v12 STATA program, and significance was set at a p value of <0.05. RESULTS: Medical student enrollment ranged from 54 to 266 students (mean = 158 ± 16). Of these students, 4.9 ± 0.6 % ranked psychiatry as their first choice for residency. Final match results yielded similar numbers at 5.0 ± 0.6 %. Ten out of 17 programs filled all psychiatry residency positions, whereas the remaining 7 programs had vacancy rates from 5 to 100 % (mean = 43.4 ± 15.1 %). Medical students were exposed to an average of 2.8 ± 0.5 pre-clerkship psychiatry weeks and 6.2 ± 0.3 clerkship weeks. Linear regression analysis demonstrated that the percentage of graduating medical students entering a psychiatry residency program could be predicted from the number of weeks of pre-clerkship exposure (p = 0.01; R(2) = 0.36) but not from the number of clerkship weeks (p = 0.74). CONCLUSIONS: This study indicates that the duration of pre-clerkship exposure to psychiatry predicts the number of students selecting psychiatry as their first choice as a discipline. Thus, increasing the duration of pre-clerkship exposure may increase the enrollment of medical students into psychiatry.

Is sleep-disordered breathing associated with miscarriages? An emerging hypothesis.

Sleep-disordered breathing (SDB) is a common disorder that has numerous medical consequences including cardiovascular morbidity. The clinical presentation in women is frequently vague, leading to its under-recognition in this population. Sleep is known to influence several female hormonal cycles including estrogen, progesterone, prolactin, luteinizing hormone (LH), and follicle stimulating hormone (FSH); consequently, sleep disruption may have adverse effects on female health including pregnancy. Miscarriage, defined as the loss of a pregnancy in the first trimester, occurs in one in four pregnancies; in up to half of cases, the cause may be unknown. Risk factors for miscarriage include increased age, increased weight, and a history of polycystic ovarian syndrome, all of which are also risk factors for SDB. Since SDB is frequently accompanied by sleep fragmentation and intermittent hypoxemia, we speculate that these factors may contribute to miscarriage risk. If this is the case, then treatment of SDB may be a possible intervention for subsequent pregnancies.