Cognitive behavior therapy for insomnia for untreated hypertension with comorbid insomnia disorder: The SLEEPRIGHT clinical trial.

Insomnia and poor sleep are associated with an increased risk of developing cardiovascular disease (CVD) and its precursors, including hypertension. In 2022, the American Heart Association (AHA) added inadequate sleep to its list of health behaviors that increase the risk for CVD. It remains unknown, however, whether the successful treatment of insomnia and inadequate sleep can reduce heightened CVD risk. SLEEPRIGHT is a single-site, prospective clinical trial designed to evaluate whether the successful treatment of insomnia results in improved markers of CVD risk in patients with untreated hypertension and comorbid insomnia disorder. Participants (N = 150) will undergo baseline assessments, followed by a 6-week run-in period after which they will receive cognitive behavior therapy for insomnia (CBT-I), comprised of 6 hourly sessions with an experienced CBT-I therapist over a 6-week period. In addition to measures of insomnia severity, as well as both subjective and objective measures of sleep, the primary outcome measures are nighttime blood pressure (BP) and BP dipping assessed by 24-h ambulatory BP monitoring (ABPM). Secondary outcomes include several CVD risk biomarkers, including clinic BP, lipid profile, vascular endothelial function, arterial stiffness, and sympathetic nervous system (SNS) activity. Data analysis will evaluate the association between improvements in insomnia and sleep with primary and secondary CVD risk biomarker outcomes. The SLEEPRIGHT trial (ClinicalTrials.Gov NCT04009447) will utilize CBT-I, the current gold standard treatment for insomnia disorder, to evaluate whether reducing insomnia severity and improving sleep are accompanied by improved biomarkers of CVD risk in patients with untreated hypertension.

Nightmares: an independent risk factor for cardiovascular disease?

STUDY OBJECTIVES: Prior work has established associations between post-traumatic stress disorder (PTSD), disrupted sleep, and cardiovascular disease (CVD), but few studies have examined health correlates of nightmares beyond risks conferred by PTSD. This study examined associations between nightmares and CVD in military veterans. METHODS: Participants were veterans (N = 3468; 77% male) serving since September 11, 2001, aged 38 years (SD = 10.4); approximately 30% were diagnosed with PTSD. Nightmare frequency and severity were assessed using the Davidson Trauma Scale (DTS). Self-reported medical issues were assessed using the National Vietnam Veterans Readjustment Study Self-report Medical Questionnaire. Mental health disorders were established using the Structured Clinical Interview for DSM-IV. The sample was stratified by the presence or absence of PTSD. Within-group associations between nightmare frequency and severity and self-reported CVD conditions, adjusting for age, sex, race, current smoking, depression, and sleep duration. RESULTS: Frequent and severe nightmares during the past week were endorsed by 32% and 35% of participants, respectively. Those endorsing nightmares that were frequent, severe, and the combination thereof were more likely to also evidence high blood pressure (ORs 1.42, OR 1.56, and OR 1.47, respectively) and heart problems (OR 1.43, OR 1.48, and OR 1.59, respectively) after adjusting for PTSD diagnosis and other covariates. CONCLUSIONS: Nightmare frequency and severity among veterans are associated with cardiovascular conditions, even after controlling for PTSD diagnosis. Study findings suggest that nightmares may be an independent risk factor for CVD. Additional research is needed to validate these findings using confirmed diagnoses and explore potential mechanisms.

Acculturation Stress, Age at Immigration, and Employment Status as Predictors of Sleep Among Latinx Immigrants.

Sleep is important for physical and mental health. Latinx individuals are thought to experience worse sleep and associated health outcomes, resulting in health disparities. There is a dearth of research on the factors (e.g., employment status, age at immigration) that predict poor sleep among Latinx immigrants. The present study aimed to (1) examine the link between demographic factors, immigration-related factors, and acculturation stress, and sleep, and (2) identify factors that either attenuate or intensify the link between acculturation stress and sleep among Latinx immigrants in the US South, an immigrant-hostile area that is home to an increasing Latinx population that remains understudied. Hierarchical regressions were used to analyze data from 391 Latinx adult immigrants, examining the link between demographic factors, immigration-related factors, acculturation stress, and two sleep variables (sleep quality, difficulty falling asleep). Employment status and age at immigration were examined as moderators of the link between acculturation stress and sleep. Data were collected through in-person surveys. Regressions showed that acculturation stress was significantly linked to worse sleep quality (ß = 0.30, p = 0.001) and more difficulty falling asleep (ß = 0.41, p < 0.001), while controlling for participant characteristics. Younger age at immigration (ß = - 0.14, p = 0.005) and being unemployed (ß = - 0.13, p = 0.006) were associated with more difficulty falling asleep. Age at immigration intensified the relationship between acculturation stress and sleep quality (ß = 0.14, p = 0.005), difficulty falling asleep (ß = 0.15, p = 0.002). Reducing acculturation stress is a meaningful intervention focus, with important implications for sleep health, particularly for recent Latinx immigrants. Age at immigration and employment status are also important factors to consider when designing targeted interventions.

Actigraphy-Derived Sleep Efficiency Is Associated With Endothelial Function in Men and Women With Untreated Hypertension.

BACKGROUND: Poor sleep quality is increasingly recognized as an important and potentially modifiable risk factor for cardiovascular disease (CVD). Impaired endothelial function may be 1 mechanism underlying the association between poor sleep and CVD risk. The present study examined the relationship between objective measures of sleep quality and endothelial function in a sample of untreated hypertensive adults. METHODS: Participants were 127 men (N = 74) and women (N = 53), including 55 African Americans and 72 White Americans, aged 40-60 years (mean age, 45.3 ± 8.5 years), with untreated hypertension (systolic blood pressure 130-159 mm Hg and/or diastolic blood pressure 85-99 mm Hg). Noninvasive brachial artery flow-mediated dilation (FMD) was assessed by ultrasound. Sleep parameters, including sleep efficiency (SE), total sleep time (TST), and subjective sleep quality, were assessed over 7 consecutive days by wrist actigraphy. RESULTS: Participants averaged 7.76 ± 1 hours in bed, with an average SE of 78 ± 9%, and TST of 6 ± 1 hours. Brachial FMD averaged 3.5 ± 3.1%. In multivariate analyses controlling for sex, race, body mass index, clinic blood pressure, income, smoking, alcohol use, and baseline arterial diameter, SE was positively associated with FMD (ß = 0.28, P = 0.012). Subjective sleep quality (ß = -0.04, P = 0.63) and TST (ß = -0.11, P = 0.25) were unrelated to FMD. CONCLUSIONS: Poor sleep as indicated by low SE was associated with impaired FMD. These findings for SE are consistent with previous observations of other measures implicating poor sleep as a CVD risk factor. Interventions that improve sleep may also help lower CVD risk.

Temporal Associations between Sleep and Daytime Functioning in Parkinson's Disease: A Smartphone-Based Ecological Momentary Assessment.

OBJECTIVES/BACKGROUND: Disruptions to mood, cognition, and other daytime functioning are common and debilitating symptoms of Parkinson's disease (PD), and there is evidence that sleep problems contribute to these symptoms. However, previous studies are limited by reliance on self-reported sleep and cross-sectional designs. With the aim of assessing sleep as a possible treatment target for improving daytime functioning in PD, we used smartphone-based ecological momentary assessment (EMA) and actigraphy to investigate temporal associations between sleep (objective and subjective) and daytime functioning. PARTICIPANTS/METHODS: Twenty participants with mild-moderate PD wore actigraphs and completed sleep diaries for 14-15 days. They reported daytime functioning (anxiety, positive affect, cognitive function, fatigue, and social function) twice daily via smartphone-administered questionnaires. Multilevel modeling examined whether sleep quantity/quality predicted next-day functioning, and whether current mood (anxiety, positive affect) predicted later sleep. RESULTS: Average completion rates for sleep diaries and daytime questionnaires were 94% and 91%, respectively. Subjective sleep quality predicted next-day anxiety (B = -.75, SE = .25, p= .003), but objective sleep did not predict any daytime functioning variables (p's>.112). Positive affect predicted later subjective sleep quality (B = 0.03, SE = .01, p = .003) but not objective sleep quantity/quality (p's>.107). CONCLUSIONS: We demonstrated the feasibility of using EMA in PD. On a daily timescale, subjective sleep quality was bidirectionally associated with mood, whereas objective sleep was not associated with any daytime functioning. This discrepancy suggests that perception of sleep is important for mood in PD, which could provide targets for non-pharmacological interventions.

Circadian Rest-Activity Rhythms Predict Cognitive Function in Early Parkinson's Disease Independently of Sleep.

BACKGROUND: Cognitive impairment is a common and debilitating symptom of Parkinson's disease (PD), and its etiology is likely multifactorial. One candidate mechanism is circadian disruption. Although there is evidence of circadian abnormalities in PD, no studies have directly assessed their association with cognitive impairment. OBJECTIVES: Investigate whether circadian rest-activity rhythm is associated with cognitive function in PD independently of sleep. METHODS: Thirty-five participants with PD wore wrist actigraph monitors and completed sleep diaries for 7 to 10 days, then underwent neuropsychological testing. Rest-activity rhythm was characterized using nonparametric circadian rhythm analysis of actigraphy data. Objective sleep parameters were also estimated using actigraphy data. Hierarchical regression models assessed the independent contributions of sleep and rest-activity rhythm to cognitive performance. RESULTS: Less stable day-to-day rest-activity rhythm was associated with poorer executive, visuospatial, and psychomotor functioning, but not with memory. Hierarchical regressions showed that interdaily stability's contribution to cognitive performance was independent of sleep's contributions. Whereas sleep contributed to executive function, but not psychomotor or visuospatial performance, rest-activity rhythm stability significantly contributed to variance in all three of these domains, uniquely accounting for 14.4% to 17.6% of their performance variance. CONCLUSIONS: Our findings indicate that circadian rest-activity rhythm is associated with cognitive impairment independently of sleep. This suggests the possible utility of rest-activity rhythm as a biomarker for circadian function in PD. Future research should explore interventions to stabilize behavioral rhythms in order to strengthen circadian function, which, in turn, may reduce cognitive impairment in PD.

Episodic future thinking in generalized anxiety disorder.

Research on future-oriented cognition in generalized anxiety disorder (GAD) has primarily focused on worry, while less is known about the role of episodic future thinking (EFT), an imagery-based cognitive process. To characterize EFT in this disorder, we used the experimental recombination procedure, in which 21 GAD and 19 healthy participants simulated positive, neutral and negative novel future events either once or repeatedly, and rated their phenomenological experience of EFT. Results showed that healthy controls spontaneously generated more detailed EFT over repeated simulations. Both groups found EFT easier to generate after repeated simulations, except when GAD participants simulated positive events. They also perceived higher plausibility of negative-not positive or neutral-future events than did controls. These results demonstrate a negativity bias in GAD individuals' episodic future cognition, and suggest their relative deficit in generating vivid EFT. We discuss implications for the theory and treatment of GAD.

Cognitive Behavioral Therapy for Insomnia Comorbid With Psychiatric and Medical Conditions: A Meta-analysis.

IMPORTANCE: Cognitive behavioral therapy for insomnia (CBT-I) is the most prominent nonpharmacologic treatment for insomnia disorders. Although meta-analyses have examined primary insomnia, less is known about the comparative efficacy of CBT-I on comorbid insomnia. OBJECTIVE: To examine the efficacy of CBT-I for insomnia comorbid with psychiatric and/or medical conditions for (1) remission from insomnia; (2) self-reported sleep efficiency, sleep onset latency, wake after sleep onset, total sleep time, and subjective sleep quality; and (3) comorbid symptoms. DATA SOURCES: A systematic search was conducted on June 2, 2014, through PubMed, PsycINFO, the Cochrane Library, and manual searches. Search terms included (1) CBT-I or CBT or cognitive behavioral [and its variations] or behavioral therapy [and its variations] or behavioral sleep medicine or stimulus control or sleep restriction or relaxation therapy or relaxation training or progressive muscle relaxation or paradoxical intention; and (2) insomnia or sleep disturbance. STUDY SELECTION: Studies were included if they were randomized clinical trials with at least one CBT-I arm and had an adult population meeting diagnostic criteria for insomnia as well as a concomitant condition. Inclusion in final analyses (37 studies) was based on consensus between 3 authors' independent screenings. DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by 2 authors and pooled using a random-effects model. Study quality was independently evaluated by 2 authors using the Cochrane risk of bias assessment tool. MAIN OUTCOMES AND MEASURES: A priori main outcomes (ie, clinical sleep and comorbid outcomes) were derived from sleep diary and other self-report measures. RESULTS: At posttreatment evaluation, 36.0% of patients who received CBT-I were in remission from insomnia compared with 16.9% of those in control or comparison conditions (pooled odds ratio, 3.28; 95% CI, 2.30-4.68; P < .001). Pretreatment and posttreatment controlled effect sizes were medium to large for most sleep parameters (sleep efficiency: Hedges g = 0.91 [95% CI, 0.74 to 1.08]; sleep onset latency: Hedges g = 0.80 [95% CI, 0.60 to 1.00]; wake after sleep onset: Hedges g = 0.68; sleep quality: Hedges g = 0.84; all P < .001), except total sleep time. Comorbid outcomes yielded a small effect size (Hedges g = 0.39 [95% CI, 0.60-0.98]; P < .001); improvements were greater in psychiatric than in medical populations (Hedges g = 0.20 [95% CI, 0.09-0.30]; χ2 test for interaction = 12.30; P < .001). CONCLUSIONS AND RELEVANCE: Cognitive behavioral therapy for insomnia is efficacious for improving insomnia symptoms and sleep parameters for patients with comorbid insomnia. A small to medium positive effect was found across comorbid outcomes, with larger effects on psychiatric conditions compared with medical conditions. Large-scale studies with more rigorous designs to reduce detection and performance bias are needed to improve the quality of the evidence.

The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function.

Effect of cognitive-behavioral therapy for anxiety disorders on quality of life: a meta-analysis.

OBJECTIVE: Although cognitive-behavioral therapy (CBT) is effective for treating anxiety disorders, little is known about its effect on quality of life. To conduct a meta-analysis of CBT for anxiety disorders on quality of life, we searched for relevant studies in PubMed, PsycINFO, and the Cochrane Library and conducted manual searches. METHOD: The search identified 44 studies that included 59 CBT trials, totaling 3,326 participants receiving CBT for anxiety disorders. We estimated the controlled and within-group random effects of the treatment changes on quality of life. RESULTS: The pre-post within-group and controlled effect sizes were moderately strong (Hedges's g = 0.54 and Hedges's g = 0.56, respectively). Improvements were greater for physical and psychological domains of quality of life than for environmental and social domains. The overall effect sizes decreased with publication year and increased with treatment duration. Face-to-face treatments delivered individually and in groups produced significantly higher effect sizes than Internet-delivered treatments. CONCLUSION: CBT for anxiety disorders is moderately effective for improving quality of life, especially in physical and psychological domains. Internet-delivered treatments are less effective than face-to-face treatments in improving quality of life.

Effect of pharmacotherapy for anxiety disorders on quality of life: a meta-analysis.

PURPOSE: Pharmacotherapy is an effective treatment for anxiety disorders, but its effects on quality of life (QOL) have not been examined systematically. Our objective was to conduct an effect size analysis of pharmacological interventions on QOL outcomes in patients with DSM-IV anxiety disorders. METHODS: Manual and electronic searches using PubMed, PsycINFO, and the Cochrane Library were conducted for records from the first available date through May 1, 2013 for trials of pharmacological interventions in patients with anxiety disorders, which had measures of QOL before and after treatment. Of 1,865 entries, 93 studies were identified as potentially relevant and 32 met inclusion criteria, of which results were examined from 22 studies reporting 27 distinct pharmacological trials, representing data from 4,344 anxiety disorder patients. Data were extracted independently by multiple observers to estimate within-group and placebo-controlled random effects of the treatment changes on QOL. We hypothesized that pharmacotherapy improves QOL, which is associated with improvement in anxiety symptoms. RESULTS: Pharmacological interventions effectively improved QOL from before to after treatment (Hedges' g = 0.59), although the controlled effect size is smaller among those trials with placebo interventions (Hedges' g = 0.32). These effect sizes were robust, increased with publication year, and increased with reductions in anxiety symptoms. CONCLUSIONS: Pharmacological therapy is effective for improving QOL in anxiety disorders, and larger symptom reductions are associated with greater improvement in QOL.

D-Cycloserine as an augmentation strategy for cognitive behavioral therapy of anxiety disorders.

The goal of this review is to examine the clinical studies on d-cycloserine, a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure procedures during cognitive behavioral therapy for anxiety disorders. Although cognitive behavioral therapy and anxiolytic medications are more effective than placebo for treating anxiety disorders, there is still considerable room for further improvement. Traditional combination strategies typically yield disappointing results. However, recent studies based on translational research have shown promise to augment the neural circuitry underlying fear extinction with pharmacological means. We discuss the current state of the literature, including inconsistencies of findings and issues concerning the drug mechanism, dosing, and dose timing. D-cycloserine is a promising combination strategy for cognitive behavioral therapy of anxiety disorders by augmenting extinction learning. However, there is also evidence to suggest that d-cycloserine can facilitate reconsolidation of fear memory when exposure procedures are unsuccessful.