Neurophysiological correlates of suicidal ideation in major depressive disorder: Hyperarousal during sleep.

BACKGROUND: Suicide is a major public health concern, and a barrier to reducing the suicide rate is the lack of objective predictors of risk. The present study considers whether quantitative sleep electroencephalography (EEG) may be a neurobiological correlate of suicidal ideation. METHODS: Participants included 84 (45 female, mean age=26.6) adults diagnosed with major depressive disorder (MDD). The item that measures thoughts of death or suicide on the Quick Inventory of Depressive Symptomatology (QIDS) was used to classify 47 participants as low suicidal ideation (24 females, mean age=26.1) and 37 as high suicidal ideation (21 females, mean age=27.3). Data were obtained from archival samples collected at the University of Michigan and University of Texas Southwestern Medical Center between 2004 and 2012. Sleep EEG was quantified using power spectral analysis, and focused on alpha, beta, and delta frequencies. RESULTS: Results indicated that participants with high compared to low suicidal ideation experienced 1) increased fast frequency activity, 2) decreased delta activity, and 3) increased alpha-delta sleep after adjusting for age, sex, depression, and insomnia symptoms. LIMITATIONS: Limitations include the exclusion of imminent suicidal intent, a single suicidal ideation item, and cross-sectional archival data. CONCLUSIONS: This is one of the first studies to provide preliminary support that electrophysiological brain activity during sleep is associated with increased suicidal ideation in MDD, and may point toward central nervous system (CNS) hyperarousal during sleep as a neurobiological correlate of suicidal ideation.

Effects of Restricted Time in Bed on Antidepressant Treatment Response: A Randomized Controlled Trial.

OBJECTIVE: Antidepressant response onset is delayed in individuals with major depressive disorder (MDD). This study compared remission rates and time to remission onset for antidepressant medication delivered adjunctively to nightly time in bed (TIB) restriction of 6 hours or 8 hours for the initial 2 weeks. METHODS: Sixty-eight adults with DSM-IV-diagnosed MDD (mean ± SD age = 25.4 ± 6.6 years, 34 women) were recruited from September 2009 to December 2012 in an academic medical center. Participants received 8 weeks of open-label fluoxetine 20-40 mg and were randomized to 1 of 3 TIB conditions for the first 2 weeks: 8-hour TIB (n = 19); 6-hour TIB with a 2-hour bedtime delay (late bedtime, n = 24); or 6-hour TIB with a 2-hour rise time advance (early rise time, n = 25). Clinicians blinded to TIB condition rated symptom severity weekly. Symptom severity, remission rates, and remission onset as rated by the 17-item Hamilton Depression Rating Scale were the primary outcomes. RESULTS: Mixed effects models indicated lower depression severity for the 8-hour TIB compared to the 6-hour TIB group overall (F8, 226.9 = 2.1, P < .05), with 63.2% of 8-hour TIB compared to 32.6% of 6-hour TIB subjects remitting by week 8 (χ²1 = 4.9, P < .05). Remission onset occurred earlier for the 8-hour TIB group (hazard ratio = 0.43; 95% CI, 0.20-0.91; P < .03), with no differences between 6-hour TIB conditions. CONCLUSIONS: Two consecutive weeks of nightly 6-hour TIB does not accelerate or improve antidepressant response. Further research is needed to determine whether adequate sleep opportunity is important to antidepressant treatment response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01545843.

Sleep-disordered breathing in major depressive disorder.

Individuals with major depressive disorder often experience obstructive sleep apnea. However, the relationship between depression and less severe sleep-disordered breathing is unclear. This study examined the rate of sleep-disordered breathing in depression after excluding those who had clinically significant sleep apnea (>5 apneas∙h⁻¹). Archival data collected between 1991 and 2005 were used to assess the prevalence of sleep-disordered breathing events in 60 (31 depressed; 29 healthy controls) unmedicated participants. Respiratory events were automatically detected using a program developed in-house measuring thermal nasal air-flow and chest pressure. Results show that even after excluding participants with clinically significant sleep-disordered breathing, individuals with depression continue to exhibit higher rates of sleep-disordered breathing compared with healthy controls (depressed group: apnea-hypopnea index mean = 0.524, SE = 0.105; healthy group: apnea-hypopnea index mean = 0.179, SE = 0.108). Exploratory analyses were also conducted to assess for rates of exclusion in depression studies due to sleep-disordered breathing. Study exclusion of sleep-disordered breathing was quantified based on self-report during telephone screening, and via first night polysomnography. Results from phone screening data reveal that individuals reporting depression were 5.86 times more likely to report a diagnosis of obstructive sleep apnea than presumptive control participants. Furthermore, all of the participants excluded for severe sleep-disordered breathing detected on the first night were participants with depression. These findings illustrate the importance of understanding the relationship between sleep-disordered breathing and depression, and suggest that screening and quantification of sleep-disordered breathing should be considered in depression research.

Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls.

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean ± SD age: 36.0 ± 11.0 yrs of age, 10 women) who were 3-12 wks since their last drink (abstinence: 57.9 ± 19.3 d) and 19 age- and sex-matched HCs (34.4 ± 10.6 yrs, 5 women). Following a 23:00-06:00 h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00 h bedtime) during which salivary melatonin samples were collected every 30 min beginning at 19:30 h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02 ± 00:41 h, than in HC, 20:44 ± 00:21 h (t = -2.4, p = .02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18 min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats.

The influence of emerging low mood symptoms on sleep in children: a pilot study.

PURPOSE: Sleep disturbances can lead to the onset and relapse of psychiatric disorders. However, the age at which this relationship begins and the role of sleep disturbances in the trajectory to the onset of a psychiatric disorder are still not fully understood. The purpose of this study was to explore, based on self- and parental-reports of mood symptoms, subjective and objective sleep in young children who are at risk of developing a psychiatric disorder but who have not yet met diagnostic criteria. PATIENTS AND METHODS: Twenty-one children (eleven girls) between the ages of 8 and 11 (mean age = 9.7 years, standard deviation = 1.1 years) were dichotomized into low mood (LM) and not low mood (NLM) groups based on scoring below or above the median threshold score on at least two of the following questionnaires: the Child Depressive Rating Scale (CDRS), Weinberg Screening Affective Scale (WSAS), and Quick Inventory of Depressive Symptomatology (QIDS). The children completed sleep diaries and underwent two nights (for adaptation and baseline) of polysomnography. Sleep stages and sleep microarchitecture (alpha, sigma, beta, and delta) in the first half of the night, were analyzed. RESULTS: Self-reported sleep disturbance accounted for 72% of the variance (F[3, 20] = 15, P < 0.005) of the Weinberg Screening Affective Scale in LM children. LM children had fewer arousals at night, but awakened earlier than NLM children. Regardless of mood, girls had more sleep disturbance, as well as lower alpha, beta, and delta power in the first half of the night, compared to boys. Girls with LM had shorter sleep times and a lower percentage of rapid eye movement sleep. CONCLUSIONS: Girls with and without LM, and without a clinical diagnosis of depression, showed more sleep disturbances than boys of the same age. Sleep disturbances evident early in life and in LM girls may reflect greater risk for future sleep or psychiatric disorders.

Sleep and body mass index in depressed children and healthy controls.

OBJECTIVE: Higher body mass index (BMI) has been associated with more sleep disturbance and depressive symptoms, but the combined effects of depression and BMI on sleep have not been studied in children. This study evaluated the relationship between BMI and polysomnography in children with major depressive disorder (MDD), compared to healthy controls (HCs). METHOD: The sample of 104 subjects included 72 children, 8-17 years old, with MDD and 32 similarly aged HCs with no personal or family history of psychopathology. BMI was adjusted using the CDC formula for percentiles by age. Subjects were categorized as (1) normal weight (5-84th percentile) or (2) high weight, which included at risk of overweight and overweight (> or = 85th percentile). All analyses were adjusted for sex and Tanner maturational stage scores. RESULTS: In the MDD group only, higher BMI was significantly correlated with decreased sleep efficiency, decreased percentage of rapid eye movement sleep (REM%), and higher percentage of time spent awake and moving (TSPAM). In the HC group only, higher BMI correlated with higher total sleep time. Multivariate analyses revealed significant interactions between the BMI and diagnostic groups for several REM sleep parameters, such that high-weight children from the HC and MDD groups had increases and decreases in REM sleep, respectively. TSPAM increased in the high-weight MDD group, but decreased in the high-weight HC group. CONCLUSIONS: Although limited by small sample size, these findings suggest that children and adolescents with MDD and a high BMI have more fragmented sleep than other children. The increased REM sleep patterns observed with MDD in this and other studies normalized in high-weight children with MDD. Prevention and treatment strategies should target both sleep and weight as factors that can potentially influence the development and course of MDD.

Sex and age differences in sleep macroarchitecture in childhood and adolescent depression.

SUBJECT OBJECTIVE: To evaluate age and sex differences in sleep macroarchitecture in children and adolescents with major depressive disorder. DESIGN: Ninety-seven (50 F, 47 M) symptomatic unmedicated depressed outpatients were compared with 76 healthy controls (42 F, 34 M) matched for age and sex. SETTING: Participants spent 2 consecutive nights in the sleep laboratory. PARTICIPANTS: One hundred seventy-three children and adolescents, aged 8 to 18 years. MEASUREMENTS AND RESULTS: Significant group-by-age-by-sex interactions were evident for total sleep period, percentage of Stage 1 sleep, percentage of Stage 2, percentage of slow-wave sleep, and rapid eye movement (REM) sleep latency. The depressed adolescent boys had the greatest sleep disturbance with the highest amount of percentage of Stage 1 sleep, the shortest REM latency, and the least percentage of slow-wave sleep and number of minutes of slow-wave sleep in the first non-REM period. There were minimal age differences in sleep parameters between depressed children and adolescent girls. Within age groups, the sex differences were minimal in the healthy controls. The sex differences within the depressed group were substantially larger than controls. CONCLUSIONS: These findings suggest a differential developmental influence on sleep in early-onset depression that is heavily dependent on sex. Sex differences are substantially smaller in healthy individuals compared with those with depression, in agreement with previous studies in depressed adults.

Blunted circadian variation in autonomic regulation of sinus node function in veterans with Gulf War syndrome.

PURPOSE: To test the hypothesis that subtle abnormalities of the autonomic nervous system underlie the chronic symptoms reported by many Gulf War veterans, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction. METHODS: Twenty-two ill Gulf War veterans and 19 age-, sex-, and education-matched control veterans underwent measurement of circadian rhythm of heart rate variability by 24-hour electrocardiography, ambulatory blood pressure recording, Valsalva ratio testing, sympathetic skin response evaluation, sweat imprint testing, and polysomnography. Investigators were blinded to case- or control-group status. RESULTS: High-frequency spectral power of heart rate variability increased normally 2.2-fold during sleep in controls but only 1.2-fold in ill veterans (P <0.0001). In ill veterans as compared with controls, it was lower at night (P = 0.0006), higher during the morning (P = 0.007), but no different during the rest of the day (P = 0.8). The mean heart rate of ill veterans also declined less at night (P = 0.0002), and their corrected QT intervals tended to be longer over the full 24 hours (P = 0.07), particularly at night (P = 0.03). Blunting of the nocturnal heart rate dip in ill veterans was confirmed by 24-hour automatic ambulatory blood pressure monitoring (P = 0.05) and polysomnography (P = 0.03). These differences remained significant after adjusting for potential confounders. Cases and controls were similar on measures of sympathetic adrenergic and sudomotor function, sleep architecture, respiratory function, and circadian variation in blood pressure and body temperature. CONCLUSION: Some symptoms of Gulf War syndrome may be due to subtle autonomic nervous system dysfunction.

Sleep microarchitecture as a predictor of recurrence in children and adolescents with depression.

Although polysomnographic abnormalities are prevalent in adults with major depressive disorders (MDD), the findings in children and adolescents have been more equivocal. Polysomnographic measures may be of predictive value in assessing course of illness. The present study used standard sleep measures and temporal coherence of sleep electroencephalogram (EEG) rhythms to predict recovery and recurrence in a 1-yr naturalistic follow-up in 47 children and adolescents 8-18 yr of age with MDD. Standard sleep measures did not predict clinical course. On the other hand, temporal coherence measures discriminated between those who recovered, recovered but recurred, and those who did not recover from the index episode. Specifically, coherence between beta, theta and delta recorded in the right hemisphere was significantly lower in the no-recovery group. In addition, temporal coherence was strongly associated with both time to recovery and recurrence. Those with the lowest coherence were less likely to recover or recurred sooner. Significant sex differences were found with a stronger relationship between temporal coherence and clinical course in boys. This study supports the use of quantitative sleep EEG measures as a predictor of clinical course in depression.

Quantitative EEG amplitude across REM sleep periods in depression: preliminary report.

OBJECTIVE: To determine if there are significant differences in the temporal organization of rapid eye movement (REM) sleep microarchitecture between healthy controls and outpatients with major depressive disorder (MDD). METHODS: Forty age-matched subjects, 20 men and 20 women, half with MDD, were selected from an archive of sleep electroencephalography (EEG) data collected under identical conditions. Each participant spent 2 consecutive nights in the Sleep Study Unit of the University of Texas Southwestern Medical Center at Dallas, the first of which served as adaptation. The average amplitude in each of 5 conventional EEG frequency bands was computed for each REM period across the second night. Data were then coded for group and sex. RESULTS: Aside from REM latency, none of the key sleep macroarchitectural variables differentiated MDD patients from controls. REM latency was longest in men with MDD. Sleep microarchitecture, however, did show a number of between-group differences. In general, slower frequencies declined across REM periods, with a significant REM period effect for delta, theta and alpha amplitude. Group x sex interactions were also obtained for theta and alpha. Beta activity showed a unique temporal profile in each group, supported by a significant REM period x group x sex interaction. In addition, the temporal change in theta amplitude across REM periods was most striking in women with MDD. CONCLUSIONS: This study suggests that, like during non-REM sleep, EEG amplitude shows a systematic temporal change over successive REM sleep periods and also shows elements that are both disease- and sex-dependent.

Sleep EEG, depression and gender.

Despite clear evidence of an intimate connection between sleep, major depressive disorders (MDD) and gender, few studies have explored gender differences in either sleep or in wakefulness in patients as a means of better understanding the psychogenic components of MDD. Indeed, few sleep studies focus on characterising gender differences in any population. This paper will present a review of the literature on gender differences in sleep and depression. The theoretical and clinical implications of the findings will also be discussed. The premise of the present review is that there is an inherent increased vulnerability to depression in women that arises out of basic gender differences in brain organisation and state regulation, particularly in response to a "biological challenge" during sleep. It is argued that the inherent properties of organisation and regulation of sleep EEG in healthy men and women, elicited under challenge conditions, show gender-specific vulnerability to organisational abnormalities that model homeostatic abnormalities in depressed men and women and contribute to the genesis of depression. 2001 Harcourt Publishers Ltd