Search

Background: Insomnia symptoms are pervasive and persistent in alcohol use disorder (AUD), though little is known about the mechanisms that underlie this association. We previously found that cognitive behavioral therapy for insomnia (CBT‐I) reduced alcohol‐related problems among veterans by improving insomnia severity (NCT03806491). In this planned secondary analysis of the same clinical trial data, we tested negative emotionality as one potential mechanism to explain this effect. Specifically, we tested the change in negative emotionality as a mediator of the association between change in insomnia symptoms and alcohol‐related outcomes (craving, heavy drinking frequency, and alcohol‐related problems). Methods: Participants were 67 veterans in treatment for AUD who also met the criteria for insomnia disorder (91% male, 84% White, average age = 46.3 years). Participants were randomized to five sessions of CBT‐I or a single‐session sleep hygiene control. Assessments occurred at baseline, immediately posttreatment (~6 weeks after baseline), and at 6‐week follow‐up. Measures included the Insomnia Severity Index, Penn Alcohol Craving Scale, Timeline Followback, and Short Inventory of Problems. We created a latent negative emotionality indicator based on five validated and reliable measures of negative emotionality. Results: Contrary to hypotheses, CBT‐I did not improve negative emotionality relative to sleep hygiene control. However, across both treatment conditions, decreases in insomnia symptoms from baseline to posttreatment were associated with concurrent decreases in negative emotionality, which in turn predicted reductions in alcohol craving and heavy drinking. Conclusion: Negative emotionality may help explain links between insomnia symptoms and alcohol‐related outcomes. [ABSTRACT FROM AUTHOR]

Background: Older adults with heart failure are at elevated risk of Alzheimer's disease and related dementias (AD/ADRD). Research suggests that insomnia and depressive episodes contribute somewhat dissociable impacts on risk for AD/ADRD in this patient population, although the temporal ordering of effects is unknown. Objective: This study examined time to dementia diagnosis among patients with comorbid insomnia and/or depressive episodes in an epidemiological sample. Methods: Secondary data analyses were conducted using a cohort study of 203,819 Veterans with a primary admission diagnosis of heart failure in 129 VA Medical Centers. Results: Patients with diagnoses of both insomnia and depressive episodes had the shortest time to a dementia diagnosis at both 1-year (Hazard ratio = 1.43, 95% CI [1.36, 1.51]) and 3-year follow-up time points (Hazard ratio = 1.40, 95% CI [1.34, 1.47]) versus patients with one or neither comorbidity. Conclusions: Individuals with both comorbidities had the shortest time to dementia onset. Screening for these comorbidities may help to identify patients at elevated risk of dementia who could benefit from enhanced monitoring or early intervention strategies for more rapid detection and management of dementia symptoms. [ABSTRACT FROM AUTHOR]

Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the TAS2R38 gene. Three SNPs form two common (AVI, PAV) and four rare haplotypes (AAI, AAV, PVI, and PAI). AVI homozygotes exhibit higher detection thresholds and lower suprathreshold bitterness for PROP compared to PAV homozygotes and heterozygotes, and these differences may influence alcohol and vegetable intake. Within a diplotype, substantial variation in suprathreshold bitterness persists, and some AVI homozygotes report moderate bitterness at high concentrations. A second receptor encoded by a gene containing a functional polymorphism may explain this. Early work has suggested that PROP might activate TAS2R4 in vitro, but later work did not replicate this. Here, we identify three TAS2R4 SNPs that result in three diplotypes—SLN/SLN, FVS/SLN, and FVS/FVS—which make up 25.1%, 44.9%, and 23.9% of our sample. These TAS2R4 haplotypes show minimal linkage disequilibrium with TAS2R38, so we examined the suprathreshold bitterness as a function of both. The participants (n = 243) rated five PROP concentrations in duplicate, interleaved with other stimuli. As expected, the TAS2R38 haplotypes explained ~29% (p < 0.0001) of the variation in the bitterness ratings, with substantial variation within the haplotypes (AVI/AVI, PAV/AVI, and PAV/PAV). Notably, the TAS2R4 diplotypes (independent of the TAS2R38 haplotypes) explained ~7–8% of the variation in the bitterness ratings (p = 0.0001). Given this, we revisited if PROP could activate heterologously expressed TAS2R4 in HEK293T cells, and calcium imaging indicated 3 mM PROP is a weak TAS2R4 agonist. In sum, our data are consistent with the second receptor hypothesis and may explain the recovery of the PROP tasting phenotype in some AVI homozygotes; further, this finding may potentially help explain the conflicting results on the TAS2R38 diplotype and food intake. [ABSTRACT FROM AUTHOR]

This randomized clinical trial assesses the efficacy of cognitive behavioral therapy for insomnia in veterans receiving treatment for alcohol use disorder. Key Points: Question: Is cognitive behavioral therapy for insomnia (CBT-I) feasible and efficacious early in treatment for alcohol use disorder, and if so, does it affect alcohol use? Findings: In this randomized clinical trial involving veterans with insomnia who were in treatment for alcohol use disorder, CBT-I was associated with greater reductions in insomnia symptoms and alcohol-related problems over time than a single session of instruction about sleep hygiene. No group differences emerged for abstinence or heavy-drinking frequency. Meaning: Long-term abstinence may not be required to derive benefit from CBT-I, which is feasible early in alcohol use disorder treatment and may reduce alcohol-related harm. Importance: Three of 4 adults in treatment for alcohol use disorder (AUD) report symptoms of insomnia. Yet the first-line treatment for insomnia (cognitive behavioral therapy for insomnia, CBT-I) is often delayed until abstinence is established. Objective: To test the feasibility, acceptability, and preliminary efficacy of CBT-I among veterans early in their AUD treatment and to examine improvement in insomnia as a mechanism for improvement in alcohol use outcomes. Design, Setting, and Participants: For this randomized clinical trial, participants were recruited through the Addictions Treatment Program at a Veterans Health Administration hospital between 2019 and 2022. Patients in treatment for AUD were eligible if they met criteria for insomnia disorder and reported alcohol use in the past 2 months at baseline. Follow-up visits occurred posttreatment and at 6 weeks. Interventions: Participants were randomly assigned to receive 5 weekly sessions of CBT-I or a single session about sleep hygiene (control). Participants were asked to complete sleep diaries for 7 days at each assessment. Main Outcomes and Measures: Primary outcomes included posttreatment insomnia severity (assessed using the Insomnia Severity Index) and follow-up frequency of any drinking and heavy drinking (4 drinks for women, ≥5 drinks for men; number of days via Timeline Followback) and alcohol-related problems (Short Inventory of Problems). Posttreatment insomnia severity was tested as a mediator of CBT-I effects on alcohol use outcomes at the 6-week follow-up. Results: The study cohort included 67 veterans with a mean (SD) age of 46.3 years (11.8); 61 (91%) were male and 6 (9%) female. The CBT-I group included 32 participants, and the sleep hygiene control group 35 participants. Of those randomized, 59 (88%) provided posttreatment or follow-up data (31 CBT-I, 28 sleep hygiene). Relative to sleep hygiene, CBT-I participants reported greater decreases in insomnia severity at posttreatment (group × time interaction: −3.70; 95% CI, −6.79 to −0.61) and follow-up (−3.34; 95% CI, −6.46 to −0.23) and greater improvements in sleep efficiency (posttreatment, 8.31; 95% CI, 1.35 to 15.26; follow-up, 18.03; 95% CI, 10.46 to 25.60). They also reported greater decreases in alcohol problems at follow-up (group × time interaction: −0.84; 95% CI, −1.66 to −0.02), and this effect was mediated by posttreatment change in insomnia severity. No group differences emerged for abstinence or heavy-drinking frequency. Conclusions and Relevance: In this randomized clinical trial, CBT-I outperformed sleep hygiene in reducing insomnia symptoms and alcohol-related problems over time but had no effect on frequency of heavy drinking. CBT-I should be considered a first-line treatment for insomnia, regardless of abstinence. Trial Registration: ClinicalTrials.gov Identifier: NCT03806491 [ABSTRACT FROM AUTHOR]

There is growing evidence that a functional polymorphism in the serotonin transporter gene (5-HTTLPR) moderates the impact of negative life events (e.g., childhood abuse) on the development of depression. However, it is unclear whether the gene x environment interaction predicts suicide attempts specifically. In addition, previous studies have not examined different forms of childhood abuse separately. In the current study, we found that 5-HTTLPR genotype moderated the link between childhood physical and sexual, but not emotional, abuse and adult psychiatric inpatients' histories of suicide attempts.

Background: Hospitalization with heart failure (HF) may signal an increased risk of Alzheimer's disease and related dementias (ADRD). Nursing homes routinely assess cognition but the association of these results with new ADRD diagnosis in a population at high risk of ADRD is not known. Objective: To determine the association between nursing home cognitive assessment results and new diagnosis of dementia after heart failure hospitalization. Methods: This retrospective cohort study included Veterans hospitalized for HF and discharged to nursing homes, from 2010 to 2015, without a prior diagnosis of ADRD. We determined mild, moderate, or severe cognitive impairment using multiple items of the nursing home admission assessment. We used Cox regression to determine the association of cognitive impairment with new ADRD diagnosis during 365 days of follow-up. Results: The cohort included 7,472 residents, new diagnosis of ADRD occurred in 4,182 (56%). The adjusted hazard ratio of ADRD diagnosis was 4.5 (95% CI 4.2, 4.8) for the mild impairment group, 5.4 (95% CI 4.8, 5.9) for moderate impairment, and 4.0 (95% CI 3.2, 5.0) for severe impairment compared to the cognitively intact group. Conclusion: New ADRD diagnoses occurred in more than half of Veterans with HF admitted to nursing homes for post-acute care. [ABSTRACT FROM AUTHOR]