The relationships between improvements in daytime sleepiness,fatigue and depression and psychomotor vigilance task testing with CPAP use in patients with obstructive sleep apnea

ObjectiveThe purpose of this study was to determine if the subjective improvements in daytime sleepiness, fatigue and depression experienced by patients with obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) therapy predict an objective improvement in vigilance, and whether patients with mild-to-moderate OSA differ from patients with severe OSA in this regard.MethodsA total of 182 patients underwent psychomotor vigilance task (PVT) testing and measurements of subjective daytime sleepiness, fatigue and depression at baseline and after a minimum of one month of adherent CPAP use at an adequate pressure.ResultsPatients with both mild-to-moderate (n = 92) and severe (n = 90) OSA experienced improvements in subjective daytime sleepiness, fatigue and depression, but objective improvement in vigilance was only seen in patients with severe OSA. In patients with severe OSA, while a correlation was found between improvements in daytime sleepiness and some PVT parameters, changes in subjective daytime sleepiness, fatigue and depression scores were not predictive of objective improvement in vigilance while controlling for all these subjective symptoms and for age, gender, body mass index, apnea-hypopnea index/respiratory event index and total sleep time/total recording time with pulse oximetry below 90%.ConclusionsWe found no predictive relationship between subjective improvements in daytime sleepiness, fatigue and depression and objective vigilance with CPAP use in patients with OSA. These results suggest that subjective complaints of daytime impairment and objective measures of vigilance in patients with OSA should be assessed separately while evaluating the efficacy of CPAP therapy on daytime functioning.     

Periodic limb movements in sleep: Prevalence and associated sleepiness in the Wisconsin Sleep Cohort

Objectives

Periodic limb movements in sleep (PLMS) are thought to be prevalent in elderly populations, but their impact on quality of life remains unclear. We examined the prevalence of PLMS, impact of age on prevalence, and association between PLMS and sleepiness.

Sleep-related intermittent hypoxia is associated with decreased psychomotor vigilance in Japanese community residents

BackgroundSleep disordered breathing (SDB) is associated with decreased psychomotor vigilance (hereafter “vigilance”) in clinical settings, but this association has yet to be confirmed in the general population. The aim of this study is to determine the associations between SDB and vigilance in a large sample of community-based participants.MethodsThe study sample consisted of 1508 community-dwelling Japanese persons (age: 30–79 years, women: 62.7%, mean body mass index [BMI]: 23.1 kg/m²). Vigilance was measured by the psychomotor vigilance task (PVT), and SDB was measured by overnight pulse oximetry. We investigated odds ratios for “high mean reaction time (RT)” and “high number of lapses,” which we defined as the 75th percentile of each value, across categories of oximetry values (three percent oxygen desaturation index [ODI], 4% ODI, average oxygen saturation, minimum oxygen saturation).ResultsMultivariable-adjusted odds ratios of high mean RT and high number of lapses in severe SDB (3% ODI ≥ 30.0 events/h) were 3.0 (95% confidence interval: 1.0–8.9; P for trend = 0.03) and 3.3 (95% confidence interval: 1.2–9.2, P for trend = 0.03), respectively, compared to participants without SDB. Similar associations were observed between PVT metrics and four percent ODI. No significant associations between average oxygen saturation and PVT metrics were observed. Minimum oxygen saturation was significantly associated with the trend of high number of lapses (P for trend = 0.007), but not with high mean RT.ConclusionsThe present study provides evidence that the intermittent hypoxia in SDB is significantly associated with the deterioration of PVT outcome metrics.     

Inflammatory markers are associated with decreased psychomotor speed in patients with major depressive disorder

Previous data have demonstrated that administration of inflammatory cytokines or their inducers leads to altered basal ganglia function associated with reduced psychomotor speed. Decreased psychomotor speed, referred to clinically as psychomotor retardation, is a cardinal symptom of major depressive disorder (MDD) and has been associated with poor antidepressant treatment response. We therefore examined the association between plasma inflammatory markers and psychomotor speed in ninety-three un-medicated patients with MDD. Psychomotor speed was assessed by a range of neuropsychological tests from purely motor tasks (e.g. movement latency and finger tapping) to those that involved motor activity with increasing cognitive demand and cortical participation (e.g. Trails A and Digit Symbol Substitution Task (DSST)). Linear regression analyses were performed to determine the relationship of inflammatory markers and psychomotor task performance controlling for age, race, sex, education, body mass index, and severity of depression. MDD patients exhibited decreased psychomotor speed on all tasks relative to normative standards. Increased IL-6 was associated with decreased performance on simple and choice movement time tasks, whereas MCP-1 was associated with decreased performance on the finger tapping task and DSST. IL-10 was associated with increased performance on the DSST. In an exploratory principle component analysis including all psychomotor tasks, IL-6 was associated with the psychomotor speed factor. Taken together, the data indicate that a peripheral inflammatory profile including increased IL-6 and MCP-1 is consistently associated with psychomotor speed in MDD. These data are consistent with data demonstrating that inflammation can affect basal ganglia function, and indicate that psychomotor speed may be a viable outcome variable for anti-inflammatory therapies in depression and other neuropsychiatric disorders with increased inflammation.     

Hypercortisolemic depression is associated with the metabolic syndrome in late-life

INTRODUCTION: Depression has been hypothesized to be associated with metabolic abnormalities which increase the risk of cardiovascular disease (CVD) and diabetes. Such a link could be due to increased HPA-axis activity. This study investigates the cross-sectional relationship between depression, urinary cortisol and metabolic syndrome in an older population. METHODS: Data are from 867 participants of the InChianti Study, aged 65 years. Depressive symptoms were assessed using the CES-D scale; cortisol levels were determined in 24-h urine samples. Metabolic syndrome was defined as three or more of the following: abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure, and high fasting glucose. RESULTS: Clinically relevant depressed mood (CES-D20) was present in 20.6% of the sample, and 24.5% had the metabolic syndrome. After adjustment for sociodemographics and health indicators, depression score (per SD increase: OR=1.20, 95% CI=1.02-1.41) and urinary cortisol level (per SD increase: OR=1.23, 95% CI=1.01-1.51) were significantly associated with presence of metabolic syndrome. There was, however, a significant interaction (p=0.003) between depressed mood and urinary cortisol in the probability of having metabolic syndrome. The odds of metabolic syndrome in persons with both depressed mood and urinary cortisol excretion in the highest tertile was 1.84 (95% CI=1.02-3.34) compared to persons with neither condition. DISCUSSION: This study suggests a synergistic relationship between depression, cortisol and metabolic syndrome. Hypercortisolemic depression may constitute a specific risk group for the metabolic syndrome.     

Posture-cognitive dual-tasking: A relevant marker of depression-related psychomotor retardation. An illustration of the positive impact of repetitive transcranial magnetic stimulation in patients with major depressive disorder

This study examined whether postural control variables, particularly the center-of-pressure (COP) velocity-based parameters, could be a relevant hallmark of depression-related psychomotor retardation (PMR). We first aimed at investigating the interplay between the PMR scores and the COP performance in patients with major depressive disorder (MDD), as compared to age-matched healthy controls; secondly, we focused on the impact of a repetitive transcranial magnetic stimulation (rTMS) treatment on depression, PMR scores and postural performance. 16 MDD patients, and a control group of 16 healthy adults, were asked to maintain quiet standing balance during two trials with or without vision, and while backward counting (dual task). All the position and velocity-based COP variables were computed. Before and after the rTMS session (n eligible MDD = 10), we assessed the depression level with the Montgomery–Asberg Depression Rating Scale (MADRS), the PMR scores with the French Retardation Rating Scale for Depression (ERD), and postural performance. Before the treatment, significant positive partial correlations were found between the pre-ERD scores and the velocity-based COP variables, especially in the dual-task conditions (p < 0.05). In contrast, there was no significant correlation between the post-ERD scores and any postural parameter after the treatment. The MADRS and ERD scores showed a significant decrease between before and after the rTMS intervention. For the first time, the findings clearly validated the view that the assessment of postural performance - easy to envisage in clinical settings-constitutes a reliable and objective marker of PMR in MDD patients.     

Major depression in late life is associated with both hypo- and hypercortisolemia.

BACKGROUND: In younger adults, depression has been associated with hypercortisolemia. In older depressed patients, however, both low and high cortisol levels have been reported. We examined the possibility of a U-shaped association between depression and cortisol in older people, suggesting both hypo- and hyperactivity of the hypothalamic-pituitary-adrenal axis. We also examined whether this might represent different depression subtypes. METHODS: This population-based study included 1185 subjects aged 65 and older. Depression was measured at both diagnostic (major depression) and symptomatic (subthreshold depression) levels of caseness. Plasma concentrations of cortisol (CORT) and corticosteroid binding globulin (CBG) were determined. From these (CORT/CBG), a free cortisol index (FCI) was computed. RESULTS: The association between cortisol and major depression was U-shaped (B CORT = -9.50 [SE 3.85] p = .014; B CORT(2) = .008 [SE .003] p = .021). Hypocortisolemic depression (lower cortisol tertile) was associated with female sex, joint diseases, and smoking. Hypercortisolemic (upper cortisol tertile) depression was associated with older age, male sex, cardiovascular diseases, nonsteroidal antiinflammatory use, and (borderline significant) cognitive impairment. CONCLUSIONS: In older people, the association between cortisol and major depression is U-shaped. Hypo- and hypercortisolemic depression may represent different depression subtypes, requiring different clinical management.     

Long sleep duration is associated with lower cognitive function among middle-age adults – the Doetinchem Cohort Study

ObjectivesIn older adults, both short and long sleep duration are associated with lower cognitive function, suggesting an inverted U-shaped association between sleep duration and cognitive outcomes. This study examined whether sleep duration is associated with (changes in) cognitive function in a middle-aged population.MethodsIn the Doetinchem Cohort Study, the cognitive function of 2970 men and women aged 41–75 years at baseline (1995–2007) was examined 2–3 times, with 5-year time intervals. Global cognitive function and the domains memory, information processing speed, and cognitive flexibility were assessed. In multivariable linear regression models, (change in) self-reported sleep duration was studied in association with the level and change in cognitive function. In a subsample of the population (n = 2587), the association of sleep duration and feeling rested with cognitive function was studied.ResultsSleep duration of 9 h and more was statistically significantly associated with lower global cognitive function (p < 0.01), memory (p = 0.02), and flexibility (p = 0.03), compared to a sleep duration of 7 or 8 h. Among adults feeling frequently not well rested, both short and long sleep duration were associated with a lower speed of cognitive function. An inverted U-shaped association between sleep duration and cognitive function was observed for speed, flexibility, and global cognitive function. Sleep duration was not associated with change in cognitive function.ConclusionsMiddle-age adults with long sleep duration had a lower cognitive function.     

Expression of Cntn1 is regulated by stress and associated with anxiety and depression phenotypes

In recent years, our understanding of neural circuits associated with depression has increased. Although inherited factors are known to influence individual differences in the risk for this disorder, it has been difficult to identify specific genes that moderate circuit functions affecting depression. Genome-wide association studies have identified genetic variants of Cntn1 that are linked to major depressive disorders. Cntn1, a subset of the neural cell adhesion protein and immunoglobulin supergene family, participates in cell contact formation and axonal growth control and plays a role in degenerative and inflammatory disorders. However, neuronal substrates that mediate Cntn1 action on depression-like phenotypes and involved mechanisms are unclear. Here, we exploited chronic unpredictable stress (CUS) exposure and found that CUS treatment significantly increased hippocampal Cntn1 messenger RNA and protein expression in both mice and rats, but not in the medial prefrontal cortex, which presented a region-specific regulation. Using an adeno-associated virus-based approach to directly overexpress Cntn1 via stereotactic injection, we demonstrated that Cntn1 overexpression in the hippocampus triggered anxiety- and depression-like phenotypes in addition to microglia activation or phagocytosis in the hippocampus, resulting in upregulation of pro-inflammatory cytokine (IL1α, IL6, and Ccl2) mRNA expression and downregulation of anti-inflammatory cytokine (IL4 and CD206) mRNA expression, determined using real-time quantitative PCR, thus impairing hippocampal immature neurons in the dentate gyrus, determined using immunohistochemical staining for doublecortin, a specific marker for immature neurons. Collectively, our results identified Cntn1 as a novel risk gene involved in regulating anxiety and depression via functional actions in the hippocampus that is correlated with microglial activation or phagocytosis and reduced hippocampal immature neurons. These results may provide a better understanding of the pathophysiological mechanisms underlying the risk of depression-related disorders.     

Childhood maltreatment is associated with depression but not with hypochondriasis in later life

Objective

Previous studies demonstrated that a history of childhood trauma is linked to mental disorders in adulthood, particularly to depression. Adverse childhood experiences are also considered to contribute to the risk of hypochondriasis, but the results of previous studies have not been conclusive with respect to the strength and specificity of this association. Therefore, we compared the association of adverse childhood experiences with both hypochondriasis and depression.

Methods

Fifty-eight patients with hypochondriasis, 52 patients with depression, and 52 healthy control participants completed the Childhood Trauma Questionnaire (CTQ) which assesses 5 varieties of abuse and neglect. A clinical interview (SCID-I) was used to establish DSM-IV diagnoses. Associations between childhood maltreatment, hypochondriasis and depression were estimated by means of analyses of variance and multiple linear regression analyses.

Results

In comparison to hypochondriacal and healthy participants, patients with a current depressive disorder reported more emotional abuse as well as more emotional and physical neglect during childhood. Patients with hypochondriasis reported more emotional neglect than healthy individuals. However, when predicting the CTQ trauma types by diagnostic category adjusting for sex and comorbid DSM-IV diagnoses, emotional abuse, emotional neglect, physical abuse, physical neglect, as well as the CTQ total score were significantly associated with depression, but none of the CTQ scores was significantly related to hypochondriasis.

Conclusions

The findings suggest a robust association of childhood maltreatment with depression but not with hypochondriasis. This result does not support etiological models of hypochondriasis which rely on childhood maltreatment as a risk factor for the development of this disorder.     

Severe insomnia is associated with more severe presentation and greater functional deficits in depression

Depression is among the most common reasons for seeking psychiatric treatment, and insomnia symptoms are common in the clinical picture of depression. The present study examines the clinical presentation and psychosocial functioning among depressed outpatients with severe symptoms of insomnia in comparison to depressed outpatients without severe insomnia symptoms. The present sample included 2900 treatment-seeking individuals, with 1057 patients having a principal diagnosis of Major Depressive Disorder (MDD). All patients were evaluated using the Structured Clinical Interview for DSM-IV Disorders (SCID), Schedule for Affective Disorders (SADS), and self-report measures of mood and psychosocial functioning. SADS Insomnia ratings were used to determine the presence of severe insomnia symptoms. Clinical, demographic, and psychosocial variables were obtained from the SCID and self-report measures. Among the patients with MDD, 24.7% endorsed severe insomnia symptoms. These individuals were older at time of presentation, were less likely to be married, had a lower education level, had a longer duration of the current depressive episode, were rated as more severe on the CGI, had poorer current functioning via GAF, and had higher HAM-D 21 scores. After controlling for severity, MDD patients with severe insomnia symptoms had poorer social functioning over the past 5 years, though this did not reach the significance level of p < .01, and significantly lower scores on 3 of the 8 SF-36 subscales (p < 0.01). These findings indicate that severe insomnia symptoms are associated with poorer psychosocial functioning and a more severe clinical presentation in patients with MDD. This argues for addressing severe insomnia symptoms among depressed patients, either via behavioral treatment or pharmacologic treatment options.     

Promoter variation in the catechol-O-methyltransferase gene is associated with remission of symptoms during fluvoxamine treatment for major depression

We investigated the association between remission of depressive symptoms in fluvoxamine treatment and catechol-O-methyltransferase (COMT) gene. Sixteen SNPs in the COMT gene were investigated in 123 outpatients with major depression. Three single nucleotide polymorphisms located in the 5′ region were associated with remission in fluvoxamine-treated outpatients with moderate to severe depression.     

A history of depression in women is associated with an altered GABAergic neuroactive steroid profile

The 3α,5α- and 3α,5β-reduced metabolites of progesterone, deoxycorticosterone, and dehydroepiandrosterone (DHEA) have potent effects on neurotransmission mediated by GABA(A) receptors, and dysregulation of these receptors has been implicated in depression. Using gas chromatography-mass spectrometry, we compared neuroactive steroid concentrations in women with a history of depressive disorders, but who were in full remission at the time of testing (n=11) to never depressed women (n=17) both before and after a challenge with oral micronized progesterone (300 mg). Serum concentrations of the following were obtained: four progesterone-derived GABAergic neuroactive steroids, the precursor pregnenolone, androstenedione-derived neuroactive steroids, and the precursor DHEA. As an index of conversion of progesterone to neuroactive steroids, we also examined ratios of neuroactive steroids to progesterone following the oral progesterone challenge. Results indicated that both before and after oral progesterone, women with histories of depression showed lower concentrations of all GABAergic neuroactive steroids than never depressed women. Those with a history of depression also had lower cortisol concentrations. Because serum neuroactive steroids are mainly synthesized in the adrenals, we hypothesize that histories of depression may be associated with persistent adrenal suppression. Following the progesterone challenge, ratios of the progesterone-derived neuroactive steroids to plasma progesterone concentrations were elevated in women with depression histories, suggesting there may be an adaptive shift in the metabolism of progesterone that compensates for lower circulating neuroactive steroid concentrations.     

The P300 component decreases in a bimodal oddball task in individuals with depression: An event-related potentials study

Objective

In this study, we investigated auditory-visual stimulation-induced P300 and examined whether P300 was differentially modulated between individuals with clinical depression and healthy controls. We hypothesized that the P300 component would significantly differ between individuals with depression and healthy individuals Specifically, we predicted that the P300 component induced by the bimodal oddball task would be significantly different from that induced by the unimodal task.

Escitalopram in the treatment of anxiety symptoms associated with depression

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.     

Sleep quality is associated with weight loss maintenance status: the MedWeight study

Sleep duration and quality have been associated with many health outcomes, including weight management. We aimed to investigate the effect of self-reported sleep duration and quality on weight loss maintenance in participants of the MedWeight study, a registry of individuals that lost at least 10% of body weight in the past and either maintained the loss (maintainers: weight maintenance of at least 10% of initial weight loss) or regained it (regainers: weight ≥95% of their maximum body weight). Study participants included 528 volunteers (61% women). Sleep quantity referred to the reported duration of nocturnal sleep, as well as the frequency of mid-day naps during the last month. Sleep quality was assessed through the Athens Insomnia Scale (AIS). Reported sleep quantity was associated with weight maintenance status, but the association became non-significant when the AIS score entered the model. In specific, AIS was inversely associated with the likelihood of being a maintainer (OR = 0.89 per AIS unit, 95% CI: 0.81 – 0.98), even after adjusting for potential confounders. Sex-specific analysis revealed that the association between the AIS score and maintenance status was evident in men but not in women. Future studies are needed to confirm these results in other population groups and reveal underlying mechanisms.     

IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C

Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behaviour. Previous studies suggest that altered basal ganglia function may contribute to IFN-alpha-induced neuropsychological and behavioural changes. To further examine IFN-alpha effects on neuropsychological functions related to basal ganglia (as well as other brain regions), and explore the relationship between altered neuropsychological function and IFN-alpha-induced depression and fatigue, a selected subset of the Cambridge Neuropsychological Test Automated Battery was administered to 32 hepatitis C patients at baseline (Visit 1) and following 12 weeks (Visit 2) of either no treatment (n = 12) or treatment with IFN-alpha plus ribavirin (n = 20). Symptoms of depression and fatigue were assessed using the Montgomery-Asberg Depression Rating Scale and the Multidimensional Fatigue Inventory. Compared to control subjects, patients treated with IFN-alpha/ribavirin exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task and slower response times in the rapid visual information processing task, a task of sustained attention. Decreased motor speed on the five-choice movement segments of the reaction time task was in turn correlated with increased symptoms of depression and fatigue (R = 0.47, p < 0.05 and R = 0.48, p < 0.05, respectively). IFN-alpha/ribavirin treatment had no effects on executive function, decision time in the reaction time task, or target detection accuracy in the sustained attention task. Motor slowing and its correlation with psychiatric symptoms suggest that altered basal ganglia function may contribute to the pathogenesis of IFN-alpha-induced behavioural changes.     

抑郁症患者脑的磁共振研究

目的;采用磁共振技术（MRI）分析抑郁症患者的脑结构改变。方法：以抑郁症患者32例为病例组,正常23例为对照组,作头颅磁共振扫描。结果：病例组第3脑室横径,双侧外侧裂宽度显著增宽,透明中隔至额极距离减少。结论：抑郁症患者额、颞叶均明显萎缩。