Dampened circadian amplitude of EEG power in women after menopause.

Postmenopausal women are at high risk of developing sleep-wake disturbances. We previously reported dampened circadian rhythms of melatonin, alertness and sleep in postmenopausal compared with young women. The present study aims to further explore electroencephalography power spectral changes in the sleep of postmenopausal women. Eight healthy postmenopausal women were compared with 12 healthy, naturally ovulating, young women in their mid-follicular phase. Participants followed a regular 8-hr sleep schedule for ≥ 2 weeks prior to laboratory entry. The laboratory visit included an 8-hr baseline sleep period followed by an ultradian sleep-wake cycle procedure, consisting of alternating 1-hr wake periods and nap opportunities. Electroencephalography power spectral analysis was performed on non-rapid eye movement sleep obtained over a 48-hr period. The baseline nocturnal sleep of postmenopausal women comprised lower power within delta and sigma, and higher power within alpha bands compared with that of younger women. During nighttime naps of the ultradian sleep-wake cycle procedure, lower power within delta and sigma, and higher power within beta bands were observed in postmenopausal women. During the ultradian sleep-wake cycle procedure, postmenopausal women presented lower power of delta, theta and sigma (14-15 Hz), undetectable rhythms of delta and theta, and a dampened or undetectable rhythm of sigma (12-15 Hz) power compared with younger women. Our results support the hypothesis of a dampened circadian variation of sleep microstructure in healthy-sleeping postmenopausal women. Circadian changes with aging are potential mechanisms for increased susceptibility to develop sleep disturbances; however, further research is needed to clarify their clinical implications and contribution to insomnia.

Sleep Quality After Quetiapine Augmentation in Patients With Treatment-Resistant Depression and Personality Disorders.

PURPOSE/BACKGROUND: Quetiapine is a first-line augmenting agent for treatment-resistant depression (TRD) and is used off-label in insomnia. Quetiapine and its active metabolite norquetiapine act mostly on 5-HT2A, 5-HT2C, H1, and D2 as antagonists and on 5-HT1A as partial agonists. Patients with TRD often have comorbid personality disorder (PD), and evidence suggests an association between sleep disturbance and recovery among patients with PD. Here, we aimed to evaluate the effects of quetiapine on sleep in TRD patients with and without PD (PD+/PD-). METHODS/PROCEDURES: We reviewed health records of 38 patients with TRD (20 TRD/PD+) who had been treated with a pharmacotherapy regimen including quetiapine. Clinical outcomes were determined by comparing changes in sleep items of the Hamilton Depression Rating Scale at the beginning (T0) and after 3 months of an unchanged treatment (T3). FINDINGS/RESULTS: Patients with TRD/PD+ and TRD/PD- taking quetiapine showed significant improvement in sleep items from T0 to T3 (P < 0.001, ηp2 ≥ 0.19). There was a significant personality × time interaction for sleep-maintenance insomnia (P = 0.006, ηp2 = 0.23), with TRD/PD+ showing a greater improvement at T3 compared with TRD/PD- (P = 0.01). While exploring other sleep items, no personality × time interaction was found. In the TRD/PD- group, improvement in sleep items was associated with an overall improvement in depressive symptoms (r = 0.55, P = 0.02). IMPLICATIONS/CONCLUSIONS: Quetiapine induced greater improvements in sleep-maintenance insomnia among TRD/PD+ patients than TRD/PD-. These findings suggest quetiapine could have a therapeutic role for insomnia in PD underscoring a distinct underlying neurobiological mechanism of sleep disturbance in people living with PD.

Sex Differences in Responses to Antidepressant Augmentations in Treatment-Resistant Depression.

BACKGROUND: Women are nearly twice as likely as men to suffer from major depressive disorder. Yet, there is a dearth of studies comparing the clinical outcomes of women and men with treatment-resistant depression (TRD) treated with similar augmentation strategies. We aimed to evaluate the effects of the augmentation strategies in women and men at the McGill University Health Center. METHODS: We reviewed health records of 76 patients (42 women, 34 men) with TRD, treated with augmentation strategies including antidepressants (AD) with mood stabilizers (AD+MS), antipsychotics (AD+AP), or in combination (AD+AP+MS). Clinical outcomes were determined by comparing changes on the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery-Åsberg Depression Rating Scale (MADRS), Quick Inventory of Depressive Symptomatology (QIDS-C16), and Clinical Global Impression rating scale (CGI-S) at the beginning and after 3 months of an unchanged treatment. Changes in individual items of the HAMD-17 were also compared between the groups. RESULTS: Women and men improved from beginning to 3 months on all scales (P < .001, η p2 ≥ 0.68). There was also a significant sex × time interaction for all scales (P < .05, η p2 ≥ 0.06), reflecting a greater improvement in women compared with men. Specifically, women exhibited greater improvement in early (P = .03, η p2 = 0.08) and middle-of-the-night insomnia (P = .01, η p2 = 0.09) as well as psychomotor retardation (P < .001 η p2 = 0.16) and psychic (P = .02, η p2 = 0.07) and somatic anxiety (P = .01, η p2 = 0.10). CONCLUSIONS: The combination of AD+AP/MS generates a significantly greater clinical response in women compared with men with TRD, supporting the existence of distinct pharmacological profiles between sexes in our sample. Moreover, they emphasize the benefit of augmentation strategies in women, underscoring the benefit of addressing symptoms such as insomnia and anxiety with AP and MS.

Distinct Effects of Antidepressants in Association With Mood Stabilizers and/or Antipsychotics in Unipolar and Bipolar Depression.

PURPOSE/BACKGROUND: There is a dearth of studies comparing the clinical outcomes of patients with treatment-resistant unipolar (TRD) depression and depression in bipolar disorder (BD) despite similar treatment strategies. We aimed to evaluate the effects of the pharmacological combinations (antidepressants [AD], mood stabilizers [MS], and/or antipsychotics [AP]) used for TRD and BD at the McGill University Health Center. METHODS/PROCEDURES: We reviewed health records of 206 patients (76 TRD 130 BD) with TRD and BD treated with similar augmentation strategies including AD with MS (AD+MS) or AP (AD+AP) or combination (AD+AP+MS). Clinical outcomes were determined by comparing changes on the 17-time Hamilton Depression Rating Scale (HAMD-17), Quick Inventory of Depressive Symptomatology, and Clinical Global Impression-Severity of Illness at the beginning (T0) and after 3 months of an unchanged treatment (T3). FINDINGS/RESULTS: Baseline HAMD-17 scores in TRD were higher than in BD (P < 0.001), but TRD patients had a greater improvement at end point (P = 0.003). Antidepressants with AP generated greater reductions in HAMD-17 in TRD compared with BD (P = 0.02). Importantly, in BD patients, the addition of AD compared with other treatment strategies failed to improve the outcome. The limitations of this study include possibly unrepresentative subjects from tertiary care settings, incomplete matching of BD and TRD subjects, nonrandomized treatment with unmatched agents, doses, and times, unknown treatment adherence, and nonblinded retrospective outcome assessments. Nevertheless, the findings may reflect real-world interactions of clinically selected pharmacotherapies. IMPLICATIONS/CONCLUSIONS: Combination of augmentation strategies such as AD+AP and/or MS showed a better clinical improvement in patients with TRD compared with BD suggesting a limited evidence for AD potentiation in BD.

The Mini-Med School and Its Impact on Future Health Care Professionals' Attitudes toward Indigenous People.

Mini-Med Schools (MiMS) are an opportunity for health sciences and social work undergraduates to discuss health-related topics with Innu and Atikamekw youth in Canada. More than 500 undergraduates and 1,000 students have taken part in the project since its beginning in 2011. This study aims to assess the impact of both 1) MiMS's predeparture training and 2) the MiMS themselves on undergraduates' prejudices toward Indigenous peoples. Satisfaction of the undergraduates taking part in the activity was also assessed. Seventy-eight undergraduates were recruited and completed the Old-fashioned and Modern Prejudiced Attitudes Toward Aboriginals Scales (O-PATAS and M-PATAS) at baseline, after the pre-departure training, and after the MiMS. They also completed satisfaction surveys. This study shows a reduction of prejudices after participating to a MiMS, but no effect of a pre-departure training. The activities were overall appreciated by undergraduates and most of them would like to take part again in the MiMS.

Effects of exogenous melatonin on sleep and circadian rhythms in women with premenstrual dysphoric disorder.

We previously found normal polysomnographic (PSG) sleep efficiency, increased slow-wave sleep (SWS), and a blunted melatonin secretion in women with premenstrual dysphoric disorder (PMDD) compared to controls. Here, we investigated the effects of exogenous melatonin in five patients previously studied. They took 2 mg of slow-release melatonin 1 h before bedtime during their luteal phase (LP) for three menstrual cycles. At baseline, patients spent every third night throughout one menstrual cycle sleeping in the laboratory. Measures included morning urinary 6-sulfatoxymelatonin (aMt6), PSG sleep, nocturnal core body temperature (CBT), visual analog scale for mood (VAS-Mood), Prospective Record of the Impact and Severity of Menstrual Symptoms (PRISM), and ovarian plasma hormones. Participants also underwent two 24-hour intensive physiological monitoring (during the follicular phase and LP) in time-isolation/constant conditions to determine 24-hour plasma melatonin and CBT rhythms. The same measures were repeated during their third menstrual cycle of melatonin administration. In the intervention condition compared to baseline, we found increased urinary aMt6 (p < 0.001), reduced objective sleep onset latency (p = 0.01), reduced SWS (p < 0.001), and increased Stage 2 sleep (p < 0.001). Increased urinary aMt6 was correlated with reduced SWS (r = -0.51, p < 0.001). Circadian parameters derived from 24-hour plasma melatonin and CBT did not differ between conditions, except for an increased melatonin mesor in the intervention condition (p = 0.01). Ovarian hormones were comparable between the conditions (p ≥ 0.28). Symptoms improved in the intervention condition, as measured by the VAS-Mood (p = 0.02) and the PRISM (p < 0.001). These findings support a role for disturbed melatonergic system in PMDD that can be partially corrected by exogenous melatonin.

Impact of Mandatory Wake Time on Sleep Timing, Sleep Quality and Rest-Activity Cycle in College and University Students Complaining of a Delayed Sleep Schedule: An Actigraphy Study.

BACKGROUND: Individuals complaining of a delayed sleep schedule are expected to have shorter sleep duration and lower sleep quality when they must comply with morning obligations. The changes in the sleep schedule imposed by morning obligations may in turn decrease the stability and amplitude of their rest-activity cycle. These expectations were only partially supported in previous studies, possibly due to poor differentiation between days with mandatory or free wake times. PARTICIPANTS: Fourteen college/university students (8 women) with a complaint of a late sleep schedule and a bedtime after midnight were compared to fourteen controls with an earlier sleep schedule and no complaint. METHODS: During a week of 24-h activity recording, participants specified in their sleep diary whether their wake time was free or determined by an obligation. RESULTS: The number of nights with mandatory wake times was similar in the two groups. Groups were also similar for sleep duration and sleep quality over the 7 days of recording. Actigraphic sleep efficiency was the same in the two groups for both free and mandatory wake times, but subjective sleep quality decreased on the nights with mandatory wake time in both groups. On the nights with mandatory wake time, delayed participants had shorter sleep episodes and less total sleep time than controls. Rest-activity cycle amplitude was lower in the delayed group whether wake time was free or mandatory. CONCLUSION: Sleep duration and total sleep time differed between the two groups only when wake time was mandatory. Prior to mandatory wake times, delayed participants kept the same bedtime and shortened their sleep; sleep latency and sleep efficiency were preserved but subjective sleep quality and alertness on awakening decreased compared to nights with free wake time. Lower amplitude of the rest-activity cycle in delayed subjects may reflect lifestyle differences compared to control participants.

Home versus laboratory assessments of melatonin production and melatonin onset in young adults complaining of a delayed sleep schedule.

Recent evidence points toward an association between higher non-visual sensitivity to light and a later circadian phase in young adults complaining of a delayed sleep schedule. Light exposure in the evening may therefore induce a larger suppression of melatonin production in these individuals, which might: (a) bias home estimates of melatonin onset; and (b) decrease sleep propensity at bedtime. In this study, we compared home and laboratory melatonin onsets and production in sleep-delayed and control participants, using saliva samples collected in the 3 hr preceding habitual bedtime. The mean light intensity measured during saliva sampling at home was ~10 lux in both groups. Melatonin suppression at home was significant, averaging 31% and 24% in sleep-delayed and control individuals, respectively. Group difference in melatonin suppression was not significant. Estimates of melatonin onset were on average 27 min later at home than in laboratory conditions, with no group difference. Looking specifically at sleep-delayed participants, there was no correlation between non-visual sensitivity to light and home-laboratory differences in melatonin onsets. However, higher light sensitivity was associated with greater melatonin suppression in the hour before habitual bedtime. Greater melatonin suppression before bedtime was also associated with a later circadian phase. These results indicate that the validity of home estimates of melatonin onset is similar in sleep-delayed and in control individuals. Results also suggest that increased non-visual sensitivity to light could impact melatonin secretion in sleep-delayed individuals and contribute to a late bedtime by delaying circadian phase and decreasing sleep propensity.

Current Trends in Management of Nonsyndromic Unilateral Coronal Craniosynostosis: A Cross-sectional Survey.

BACKGROUND: Although the natural history of nonsyndromic unilateral coronal craniosynostosis has been extensively described, optimal management remains controversial due to lack of Level 1 evidence. This study aims to assess the current state of practice among craniofacial surgeons. METHODS: Ninety-four craniofacial surgeons were approached to complete a survey consisting of 15 questions. Data were collected assessing surgeons' primary surgical indication, timing of intervention, preoperative imaging, and choice of technique for patients presenting with nonsyndromic unilateral coronal craniosynostosis. Choice of technique and timing of intervention in case of recurrence were also investigated. RESULTS: After 5 mailings, the response rate was 61%. The combination of both appearance and raised intracranial pressure was the primary indication for treatment for 73.2% of surgeons. Preoperative CT scan of the skull was "always" performed by 70.1% of respondents. Open surgical management was most commonly performed at 8-10 months of age (38.6%). Bilateral frontal craniectomy with remodeling of the supraorbital bandeau and frontal bone was the most common choice of procedure (84.2%). In case of mild to moderate and moderate to severe recurrences at 1 year of age, 89.5% and 47.4% of surgeons opted for conservative management, respectively. Optimal timing for repeat cranioplasty was after 4 years of age (65.5%). Overall, 43.4% quoted lack of evidence as the greatest obstacle to clinical decision-making when dealing with unilateral synostosis. CONCLUSION: This survey exposes the lack of consensus and the disparity of opinion among craniofacial surgeons regarding the management of nonsyndromic coronal synostosis, particularly in the setting of recurrence.

Daily Profiles of Light Exposure and Evening Use of Light-emitting Devices in Young Adults Complaining of a Delayed Sleep Schedule.

A number of factors can contribute to a delayed sleep schedule. An important factor could be a daily profile of light exposure favoring a later circadian phase. This study aimed to compare light exposure between 14 young adults complaining of a delayed sleep schedule and 14 matched controls and to identify possible associations between habitual light exposure and circadian phase. Exposure to white and blue light was recorded with ambulatory monitors for 7 consecutive days. Participants also noted their daily use of light-emitting devices before bedtime. Endogenous circadian phase was estimated with the dim light melatonin onset (DLMO) in the laboratory. The amplitude of the light-dark cycle to which the subjects were exposed was smaller in delayed than in control subjects, and smaller amplitude was associated with a later DLMO. Smaller amplitude was due to both decreased exposure in the daytime and increased exposure at night. Total exposure to blue light, but not to white light, was lower in delayed subjects, possibly due to lower exposure to blue-rich outdoor light. Lower daily exposure to blue light was associated with a later DLMO. Timing of relative increases and decreases of light exposure in relation to endogenous circadian phase was also compared between the 2 groups. In delayed subjects, there was a relatively higher exposure to white and blue light 2 h after DLMO, a circadian time with maximal phase-delaying effect. Delayed participants also had higher exposure to light 8 to 10 h after DLMO, which occurred mostly during their sleep episode but may have some phase-advancing effects. Self-reported use of light-emitting devices before bedtime was higher in delayed than in control subjects and was associated with a later DLMO. This study suggests that individuals complaining of a delayed sleep schedule engage in light-related behaviors favoring a later circadian phase and a later bedtime.

Scientific Overview on CSCI-CITAC Annual General Meeting and 2016 Young Investigators' Forum.

The 2016 Annual General Meeting of the Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was a national conference held in Toronto November 21-23, 2016, in conjunction with The University of Toronto Clinician Investigator Program Research Day. The theme for this year's meeting was "Mapping Your Career as a Clinician-Scientist"; emphasizing essential skills for developing a fruitful career as clinician-scientist. The meeting featured an opening presentation by Dr. Alan Underhill, Dr. Nicola Jones and Alexandra Kuzyk. The keynote speakers were Dr. Nada Jabado (McGill University), who discussed the association between cancer and histones, Dr. Norman Rosenblum (University of Toronto), who addressed the career path and the "calling" of the Clinician Scientist, Dr. Martin Schmeing (McGill University), who was the 2016 Joe Doupe Award recipient, and Dr. Linda Rabeneck (Cancer Care Ontario and University of Toronto), who received the Friends of CIHR lectureship. The workshops, focusing on career development for clinician scientists, were hosted by Drs. Alan Underhill, Nicola Jones, Lynn Raymond, Michael Schlossmacher and Norman Rosenblum, as well as University of Toronto communication specialists, Caitlin Johannesson and Suzanne Gold. In addition, the Young Investigators' Forum included presentations from clinician investigator trainees from across the country. The research topics were diverse and comprehensive: from basic sciences to clinical practice; from epidemiology to medical engineering. All scientific abstracts are summarized in this review. Over 70 abstracts were showcased at this year's meeting during two poster sessions, with six outstanding abstracts selected for oral presentations during the President's Forum.

Eustachian Tube Obliteration and its Effect on Rhinoliquorrhea in Translabyrinthine Vestibular Schwannoma Excision.

OBJECTIVE: Rhinoliquorrhea is defined as a cerebrospinal fluid leakage from the nose. Our objective in this study is to determine the reduction of rhinoliquorrhea rates by Eustachian tube (ET) obliteration in the context of a translabyrinthine approach performed following vestibular schwannoma (VS) excision. MATERIALS AND METHODS: This is a prospective study achieved in a tertiary-care center where the chart review revealed 94 VS operated by the translabyrinthine approach between 2009 and 2015. There were 40 males and 54 females aged from 28-76 years. The only exclusion criterion was a previous history of cranial surgery. ET obliteration was systematically executed when the petrous apex pneumatization level was at least 2 of 4. Our main outcome measure was the development of rhinoliquorrhea. RESULTS: Eighty-eight patients underwent ET obliteration and were followed for an average of 2.6±1.2 years. Rhinoliquorrhea was reported in 1.14% of the patients having had an ET obliteration. When compared to our previous sample of patients operated with a translabyrinthine approach, it represents a reduction of 84%. CONCLUSION: Obliteration of the ET is a fast and simple procedure that reduces the rate of rhinoliquorrhea. We therefore recommend its use, specifically in cases of petrous apex pneumatization levels 2-4.

Circadian phase, dynamics of subjective sleepiness and sensitivity to blue light in young adults complaining of a delayed sleep schedule.

OBJECTIVE: To assess factors that might contribute to a delayed sleep schedule in young adults with sub-clinical features of delayed sleep phase disorder. METHODS: Two groups of 14 young adults (eight women) were compared: one group complaining of a delayed sleep schedule and a control group with an earlier bedtime and no complaint. For one week, each subject maintained a target bedtime reflecting their habitual sleep schedule. Subjects were then admitted to the laboratory for the assessment of circadian phase (dim light melatonin onset), subjective sleepiness, and non-visual light sensitivity. All measures were timed relative to each participant's target bedtime. Non-visual light sensitivity was evaluated using subjective sleepiness and salivary melatonin during 1.5-h exposure to blue light, starting one hour after target bedtime. RESULTS: Compared to control subjects, delayed subjects had a later circadian phase and a slower increase of subjective sleepiness in the late evening. There was no group difference in non-visual sensitivity to blue light, but we found a positive correlation between melatonin suppression and circadian phase within the delayed group. CONCLUSIONS: Our results suggest that a late circadian phase, a slow build-up of sleep need, and an increased circadian sensitivity to blue light contribute to the complaint of a delayed sleep schedule. These findings provide targets for strategies aiming to decreasing the severity of a sleep delay and the negative consequences on daytime functioning and health.