Adolescents' sleep mediates maternal depressive problems and parenting behaviors: daughter and son differences in a majority Black and Hispanic sample.

STUDY OBJECTIVES: Parents who experience depressive symptoms are less likely to use positive parenting behaviors, in part because of sad affect and inconsistency, which can lead to disengaged parenting. Their children also are more likely to get too little sleep, get too much sleep, or have trouble sleeping, leading to increased irritability and defiance, which may make it more difficult for a parent to use clear rules and result in more harsh parenting behaviors. The current study examined whether adolescents' sleep (too little, too much, trouble sleeping) mediated the relation between maternal depression and parenting behaviors (harsh parenting, positive parenting, clear rules). Further, a child's sex was examined as a moderator (ie, moderated mediation). METHODS: The sample (n = 318) consisted of mothers reporting on adolescents aged 16-18 years (mean = 16.89, standard deviation = .429; 53.4% female) from the 10th wave of the Schools and Families Educating Children Study. Measures included the Child Behavior Checklist, Center for Epidemiologic Studies Depression Scale, and the Parenting Practices Questionnaire. RESULTS: Too little sleep mediated the relation between maternal depressive problems and clear rules in the overall sample (ß = .05) and between maternal depressive problems and positive parenting (ß = .11), clear rules (ß = .13), and harsh parenting (ß = .14) for only sons. Too much sleep mediated the relation between maternal depressive problems and harsh parenting in the overall sample (ß = .03), but no mediation occurred for sons and daughters separately. Trouble sleeping did not serve as a mediator in the overall sample but mediated the relation between maternal depressive problems and clear rules for daughters (ß = .03) and between maternal depressive problems and harsh parenting for sons (ß = .09). CONCLUSIONS: These results suggest that adolescents' sleep difficulties may be one contributing factor to why mothers who are dealing with depressive symptoms have difficulty using clear rules/positive parenting and use more harsh parenting behaviors. In addition, several of these mediations differed for sons and daughters, indicating important sex differences that may help to better inform and design intervention programs for mothers experiencing depression. CITATION: Stearns MA, McCrae CS, Curtis AF, et al. Adolescents' sleep mediates maternal depressive problems and parenting behaviors: daughter and son differences in a majority Black and Hispanic sample. J Clin Sleep Med. 2024;20(6):849-858.

Preliminary investigation of the interactive role of physiological arousal and insomnia complaints in gray matter volume alterations in chronic widespread pain.

STUDY OBJECTIVES: Brain regions involved in insomnia and chronic pain are overlapping and diffuse. The interactive role of physiological arousal in associations between insomnia symptoms and neural regions is unknown. This preliminary study examined whether arousal interacted with sleep in associations with gray matter volume of frontal (dorsolateral prefrontal cortex, anterior cingulate cortex) and temporal (right/left hippocampus) regions in adults with chronic widespread pain and insomnia complaints. METHODS: Forty-seven adults with chronic widespread pain and insomnia (mean age = 46.00, standard deviation = 13.88, 89% women) completed 14 daily diaries measuring sleep onset latency (SOL), wake time after sleep onset, and total sleep time (TST), as well as Holter monitor assessments of heart rate variability (measuring physiological arousal), and magnetic resonance imaging. Multiple regressions examined whether average SOL, wake time after sleep onset, or TST were independently or interactively (with arousal/heart rate variability) associated with dorsolateral prefrontal cortex, anterior cingulate cortex, and left/right hippocampus gray matter volumes. RESULTS: Shorter TST was associated with lower right hippocampus volume. TST also interacted with arousal in its association with right hippocampal volume, Specifically, shorter TST was associated with lower volume at highest and average arousal levels. SOL interacted with arousal in its association with anterior cingulate cortex volume, such that, among individuals with lowest arousal, longer SOL was associated with lower volume. CONCLUSIONS: Preliminary findings highlight the interactive roles of physiological arousal and insomnia symptoms in associations with neural structure in chronic widespread pain and insomnia. Individuals with the highest physiological arousal may be particularly vulnerable to the impact of shorter TST on hippocampal volume loss. Reducing SOL may only impact anterior cingulate cortex volume in those with lower physiological arousal. CITATION: Curtis AF, Nair N, Hayse B, et al. Preliminary investigation of the interactive role of physiological arousal and insomnia complaints in gray matter volume alterations in chronic widespread pain. J Clin Sleep Med. 2024;20(2):293-302.

Development and Initial Evaluation of Web-Based Cognitive Behavioral Therapy for Insomnia in Rural Family Caregivers of People With Dementia (NiteCAPP): Mixed Methods Study.

BACKGROUND: Informal caregivers of people with dementia frequently experience chronic insomnia, contributing to stress and poor health outcomes. Rural caregivers are particularly vulnerable but have limited access to cognitive behavioral therapy for insomnia (CBT-I), a recommended frontline treatment for chronic insomnia. Web-based delivery promises to improve insomnia, particularly for rural caregivers who have limited access to traditional in-person treatments. Our team translated an efficacious 4-session standard CBT-I content protocol into digital format to create NiteCAPP. OBJECTIVE: This study aimed to (1) adapt NiteCAPP for dementia caregivers to create NiteCAPP CARES, a tailored digital format with standard CBT-I content plus caregiver-focused modifications; (2) conduct usability testing and evaluate acceptability of NiteCAPP CARES' content and features; and (3) pilot-test the adapted intervention to evaluate feasibility and preliminary effects on sleep and related health outcomes. METHODS: We followed Medical Research Council recommendations for evaluating complex medical interventions to explore user needs and adapt and validate content using a stepwise approach: (1) a rural dementia caregiver (n=5) and primary care provider (n=5) advisory panel gave feedback that was used to adapt NiteCAPP; (2) caregiver (n=5) and primary care provider (n=7) focus groups reviewed the newly adapted NiteCAPP CARES and provided feedback that guided further adaptations; and (3) NiteCAPP CARES was pilot-tested in caregivers (n=5) for feasibility and to establish preliminary effects. Self-report usability measures were collected following intervention. Before and after treatment, 14 daily electronic sleep diaries and questionnaires were collected to evaluate arousal, health, mood, burden, subjective cognition, and interpersonal processes. RESULTS: The stepped approach provided user and expert feedback on satisfaction, usefulness, and content, resulting in a new digital CBT-I tailored for rural dementia caregivers: NiteCAPP CARES. The advisory panel recommended streamlining content, eliminating jargon, and including caregiver-focused content. Focus groups gave NiteCAPP CARES high usefulness ratings (mean score 4.4, SD 0.79, scored from 1=least to 5=most favorable; score range 4.2-4.8). Multiple features were evaluated positively, including the intervention's comprehensive and engaging information, caregiver focus, good layout, easy-to-access intervention material, and easy-to-understand sleep graphs. Suggestions for improvement included the provision of day and night viewing options, collapsible text, font size options, tabbed access to videos, and a glossary of terms. Pilot-test users rated usefulness (mean score 4.3, SD 0.83; range 4.1-4.5) and satisfaction (mean score 8.4, SD 1.41, scored from 1=least to 10=most satisfied; range 7.4-9.0) highly. Preliminary effects on caregiver sleep, arousal, health, mood, burden, cognition, and interpersonal processes (all P<.05) were promising. CONCLUSIONS: Adaptations made to standard digital CBT-I created a feasible, tailored digital intervention for rural dementia caregivers. Important next steps include further examination of feasibility and efficacy in a randomized controlled trial with an active control condition, a multisite effectiveness trial, and eventual broad dissemination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04632628; https://clinicaltrials.gov/ct2/show/NCT04632628.

Relationship Between MR Spectroscopy-Detected Glutamatergic Neurometabolites and Changes in Social Behaviors in a Pilot Open-Label Trial of Memantine for Adults With Autism Spectrum Disorder.

Background: The neurobiology underlying ASD is largely unknown but altered neural excitability/inhibitory ratios have been reported. Memantine is an N-methyl-D-aspartate (NMDA) glutamatergic antagonist studied for the treatment of core ASD symptoms, with mixed results. We examined whether glutamatergic levels were associated with and predicted response to memantine in an exploratory pilot study. Methods: Ten adult participants with ASD underwent proton magnetic resonance spectroscopy (1H-MRS) imaging at baseline and behavioral assessments before and after 12-weeks of open-label memantine. Post-treatment scores on Clinical Global Impressions-Improvement (CGI-I) for social interaction were the primary outcome measure, and scores on the Social Responsiveness Scale (SRS) were included as a secondary outcome. LCModel was used to quantify the concentrations of Point RESolved Spectroscopy-detected glutamate+glutamine (Glx) (and other neurometabolites, i.e., N-acetylaspartate, NAA; creatine+phosphocreatine, Cr+PCr, and myo-inositol, Ins), within the left dorsolateral prefrontal cortex (LDLPFC) and right (R) posterolateral cerebellum. SPM was used to perform brain tissue segmentation within the spectroscopic voxels. CGI-I scores post-treatment were used to classify the participants into two groups, responders (scores 1-3; n = 5) and non-responders (scores 4-7, or withdrew due to increase behaviors; n = 5). Independent samples t-tests, partial correlations and linear hierarchical regression models (SPSS) were used to determine between-group differences in neurometabolite concentrations and associations between neurometabolites and behavioral scores. Results: Responders and non-responders did not significantly differ in Glx levels in any region of interest, but differed in NAA levels in LDLPFC (higher in responders vs. non-responders). Although changes in CGI-I social scores were not correlated with Glx in any region of interest, the linear hierarchical regression did reveal that Glx and Ins levels in LDLPFC were predictors of post-treatment CGI-I social scores. Changes in SRS scores were correlated with baseline Cr+PCr levels in the LDLPFC. Discussion: Our pilot data suggest that baseline Glx, a marker of glutamatergic neurotransmission, did not directly predict response to memantine for social outcomes in adults with ASD. However, interactions between Glx and the neurometabolite associated with glial integrity (Ins) may help predict treatment response. Further, those with highest baseline NAA, a putative neuronal marker, and Cr+pCr, a brain energy metabolism marker, were the best responders. These preliminary results may explain some of the mixed results reported in previous memantine trials in ASD. Future studies will need to examine these results in a larger sample.

Impact of Web-Based Cognitive Behavioral Therapy for Insomnia on Stress, Health, Mood, Cognitive, Inflammatory, and Neurodegenerative Outcomes in Rural Dementia Caregivers: Protocol for the NiteCAPP CARES and NiteCAPP SHARES Randomized Controlled Trial.

BACKGROUND: Chronic insomnia affects up to 63% of family dementia caregivers. Research suggests that chronic insomnia prompts changes in central stress processing that have downstream negative effects on health and mood, as well as on cognitive, inflammatory, and neurodegenerative functioning. We hypothesize that cognitive behavioral therapy for insomnia (CBT-I) will reverse those downstream effects by improving insomnia and restoring healthy central stress processing. Rural caregivers are particularly vulnerable, but they have limited access to CBT-I; therefore, we developed an accessible digital version using community input (NiteCAPP CARES). OBJECTIVE: This trial will evaluate the acceptability, feasibility, and short-term and long-term effects of NiteCAPP CARES on the sleep and stress mechanisms underlying poor caregiver health and functioning. METHODS: Dyads (n=100) consisting of caregivers with chronic insomnia and their coresiding persons with dementia will be recruited from Columbia and surrounding areas in Missouri, United States. Participant dyads will be randomized to 4 weeks (plus 4 bimonthly booster sessions) of NiteCAPP CARES or a web-based sleep hygiene control (NiteCAPP SHARES). Participants will be assessed at baseline, after treatment, and 6- and 12-month follow-ups. The following assessments will be completed by caregivers: 1 week of actigraphy and daily diaries measuring sleep, Insomnia Severity Index, arousal (heart rate variability), inflammation (blood-derived biomarkers: interleukin-6 and C-reactive protein), neurodegeneration (blood-derived biomarkers: plasma amyloid beta [Aß40 and Aß42], total tau, and phosphorylated tau [p-tau181 and p-tau217]), cognition (Joggle battery, NIH Toolbox for Assessment of Neurological and Behavioral Function, and Cognitive Failures Questionnaire), stress and burden, health, and mood (depression and anxiety). Persons with dementia will complete 1 week of actigraphy at each time point. RESULTS: Recruitment procedures started in February 2022. All data are expected to be collected by 2026. Full trial results are planned to be published by 2027. Secondary analyses of baseline data will be subsequently published. CONCLUSIONS: This randomized controlled trial tests NiteCAPP CARES, a web-based CBT-I for rural caregivers. The knowledge obtained will address not only what outcomes improve but also how and why they improve and for how long, which will help us to modify NiteCAPP CARES to optimize treatment potency and support future pragmatic testing and dissemination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04896775; https://clinicaltrials.gov/ct2/show/NCT04896775. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37874.

Neural activation changes in response to pain following cognitive behavioral therapy for patients with comorbid fibromyalgia and insomnia: a pilot study.

STUDY OBJECTIVES: To examine whether cognitive behavioral treatments for insomnia (CBT-I) and pain (CBT-P) lead to neural activation changes in response to pain in fibromyalgia. METHODS: Thirty-two patients with fibromyalgia (mean age = 55.9, standard deviation = 12.2) underwent an experimental pain protocol during functional magnetic resonance imaging and completed 14-day diaries assessing total wake time, total sleep time, and pain intensity before and after CBT-I, CBT-P, or waitlist control. Random effects analysis of covariance identified regions with significant group (CBT-I, CBT-P, waitlist control) by time (baseline, post-treatment) interactions in blood oxygen level-dependent response to pain. Linear regressions using residualized change scores examined how changes in total wake time, total sleep time, and pain intensity were related to activation (blood oxygen level-dependent) changes. RESULTS: Twelve regions exhibited small to moderate effects with significant interactions Ps < .00; right hemisphere: inferior frontal, middle occipital, and superior temporal gyri, insula, lentiform nucleus; left hemisphere: angular, superior temporal, midfrontal, inferior occipital, midtemporal, and inferior frontal gyri. Blood oxygen level-dependent response to pain decreased in 8 regions following CBT-I, and in 3 regions following CBT-P (CBT-I effects > CBT-P). Blood oxygen level-dependent response also increased in 3 regions following CBT-P and in 6 regions following waitlist control. Improved total wake time and/or total sleep time, not pain intensity, predicted decreased blood oxygen level-dependence in 7 regions (Ps < .05), accounting for 18%-47% of the variance. CONCLUSIONS: CBT-I prompted greater decreases in neural activation in response to pain across more regions associated with pain and sleep processing than CBT-P. Reported sleep improvements may underlie those decreases. Future research examining the longer-term impact of CBT-I and improved sleep on central pain and sleep mechanisms is warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Sleep and Pain Interventions in Fibromyalgia (SPIN); Identifier: NCT02001077; URL: https://clinicaltrials.gov/ct2/show/NCT02001077. CITATION: McCrae CS, Craggs JG, Curtis AF, et al. Neural activation changes in response to pain following cognitive behavioral therapy for patients with comorbid fibromyalgia and insomnia: a pilot study. J Clin Sleep Med. 2022;18(1):203-215.

Protocol for targeting insomnia in school-aged children with autism spectrum disorder without intellectual disability: a randomised control trial.

INTRODUCTION: Insomnia affects up to 80% of children with autism spectrum disorder (ASD). Negative consequences of insomnia in ASD include decreased quality of life (QOL), impaired learning and cognition, increased stereotypic and challenging behaviours, and increased parental stress. Cognitive behavioural treatment for childhood insomnia (CBT-CI) is a promising treatment for dealing with insomnia and its negative consequences but has not yet been studied in school-aged children with ASD and comorbid insomnia. Access to healthcare is another challenge for children with ASD, particularly in rural and underserved regions. Previous studies indicate that ASD and insomnia share common arousal-based underpinnings, and we hypothesise that CBT-CI will reduce the hyperarousal associated with insomnia and ASD. This trial will be the first to examine CBT-CI adapted for children with ASD and will provide new information about two different modes of delivery across a variety of primary and secondary child and parent sleep and related outcomes. Knowledge obtained from this trial might allow us to develop new or modify current treatments to better target childhood insomnia and ASD. METHODS AND ANALYSIS: Children (N=180) 6-12 years of age with ASD and insomnia will be recruited from an established autism database, a paediatric clinic and community outreach in the Columbia, MO and surrounding areas. Participants will be randomised to CBT-CI adapted for children with ASD (in-person or remote using computers with cameras) or Sleep Hygiene and Related Education. Participants will be assessed at baseline, post-treatment, 6-month and 12-month follow-ups. The following assessments will be completed regarding the children: objective and subjective sleep, daytime functioning (adaptive functioning, attention, challenging behaviours, anxiety), QOL and physiological arousal (heart rate variability) and parents: objective and subjective sleep, daytime functioning (anxiety, depression, fatigue), QOL, physiological arousal and parental burden/stress. ETHICS AND DISSEMINATION: Ethics approval was obtained in January 2020 from the University of Missouri. Ethics approval was obtained in July 2020 from the US Army Medical Research and Development Command, Office of Research Protections and Human Research Protection Office. All data are expected to be collected by 2024. Full trial results are planned to be published by 2025. Secondary analyses of baseline data will be subsequently published. TRIAL REGISTRATION NUMBER: NCT04545606; Pre-results.

Antipsychotics in Inpatient Children and Adolescents with Seclusion and Restraint: A Preliminary Exploratory Retrospective Chart Review.

Objective: This study is a retrospective review of patients 5-17 years of age experiencing seclusion and/or restraint (S&R) in a pediatric psychiatric inpatient setting and an exploratory analysis of antipsychotic use on S&R duration. We examined whether administration of antipsychotics would possibly decrease the time spent in S&R. Methods: Reports of patients who underwent S&R in an acute care inpatient child and adolescent psychiatric unit from 2012 to 2014 were reviewed. Demographic information related to age, gender, and race as well as information on diagnosis, current medications (including antipsychotics) were obtained. Independent samples t-tests were used to determine whether there were differences in how much time patients spent in S&R based on whether they were administered antipsychotics or not. Odds ratios (ORs) of being administered antipsychotics during S&R were computed for factors such as gender, race, and diagnosis group. Results: Ninety-six patients (68 males, age range 5-17 years) were involved in 232 S&R events that occurred between 2012 and 2014. Results indicate that patients who were administered antipsychotics during S&R still spent significantly more time in S&R compared with those who were given medications other than antipsychotics (e.g., Benadryl) (t = 3.161; p = 0.002) and those who were not administered any medication (t = 3.54; p = 0.001). Binary logistic regression showed that female patients were at more than two times (OR(adjusted) = 2.86; 95% confidence interval = 1.234-6.655) higher risk of being administered antipsychotics while in S&R compared with their male counterparts within this particular sample. Conclusions: The results of our study indicate that, contrary to our hypothesis, antipsychotic administration did not appear to reduce the time spent in S&R compared with groups that were administered medications other than antipsychotics and those that were not administered any medication during S&R. We also found an increased risk of antipsychotic administration in female patients compared with male patients in S&R events, indicating the need for larger studies examining these effects in greater detail.

Impact of a brief behavioral treatment for insomnia (BBTi) on metacognition in older adults.

INTRODUCTION: Brief (≤4 sessions) behavioral treatment for insomnia (BBTi) improves insomnia symptoms in older adults. Findings for BBTi-related improvements in objective cognition are mixed, with our recent trial reporting no effects. Metacognition (appraisal of one's own performance) has not been examined. This study examined the effects of BBTi on metacognition in older adults with insomnia. METHODS: Older adults with insomnia [N = 62, Mage = 69.45 (SD = 7.71)] were randomized to 4-weeks of BBTi (n = 32; psychoeducation, sleep hygiene, stimulus control, sleep restriction, relaxation, review/maintenance) or self-monitoring control (SMC; n = 30; social conversations). Throughout the study (2 week baseline, 4 week treatment, 2 week post-treament, 2 week 3-month followup), participants completed daily paper/pencil cognitive tasks (measuring verbal memory, attention, processing speed and reasoning) and provided daily metacognition ratings of their performance in four areas: quality, satisfaction, compared to same age peers, compared to own ability. Two-week averages of metacognitive ratings were calculated for baseline, treatment-first half, treatment-second half, post-treatment, and 3-month follow-up. Multilevel Modeling examined treatment effects (BBTi/SMC) over time on metacognition, controlling for age and sex. RESULTS: A significant group by time interaction (p = 0.05) revealed consistent improvements over time in better metacognitive ratings relative to same age peers for BBTi. Specifically, baseline ratings [mean (M) = 51.21, standard error (SE) = 3.15] improved at first half of treatment (M = 56.65, SE = 3.15, p < 0.001), maintained improvement at second-half of treatment (p = 0.18), showed additional improvement at post-treatment (M = 60.79, SE = 3.15, p = 0.02), and maintained improvement at follow-up (M = 62.30, SE = 3.15; p = 0.02). SMC prompted inconsistent and smaller improvements between baseline (M = 53.24, SE = 3.29) and first-half of treatment (M = 56.62, SE = 3.28; p = 0.004), with additional improvement at second-half of treatment (M = 59.39, SE = 3.28; p = 0.02) that was maintained at post-treatment (p = 0.73) and returned to levels observed at first-half of treatment (M = 57.78, SE = 3.21; p = 0.55). Significant main effects of time (all ps < 0.001) for other metacognition variables (Quality, Satisfaction, Compared to own ability) indicated general improvements over time for both groups. DISCUSSION: Metacognition generally improved over time regardless of treatment. BBTi selectively improved ratings of performance relative to same age peers. Repeated objective testing alone may improve metacognition in older adults with insomnia. Better understanding of metacognition and how to improve it has important implications for older adults as metacognitive complaints have been associated with mild cognitive impairment.

Telehealth cognitive behavioral therapy for insomnia in children with autism spectrum disorder: A pilot examining feasibility, satisfaction, and preliminary findings.

LAY ABSTRACT: Insomnia is common in children with autism. Cognitive behavioral treatment for childhood insomnia (CBT-CI) may improve sleep and functioning in children with autism and their parents, but typical delivery involving multiple office visits can make it difficult for some children to get this treatment. This pilot study tested telehealth delivery of CBT-CI using computers, which allowed children and their parents to get the treatment at home. This pilot shows therapists that parents and children were able to use telehealth CBT-CI to improve child and parent sleep, child behavior and arousal, and parent fatigue. Parents found telehealth CBT-CI helpful, age-appropriate, and autism-friendly. Telehealth CBT-CI holds promise for treating insomnia in school-aged children with autism and deserves further testing.

Association Between Sleep Times and Seclusion and Restraint Events in an Inpatient Pediatric Psychiatric Hospital: A Retrospective Chart Review.

OBJECTIVE: To examine demographic characteristics of patients who experience seclusion and restraint (S&R) events in a pediatric psychiatric inpatient setting and assess whether sleep time 24 hours prior and after the occurrence of an S&R event was different from average sleep time during hospitalization. METHODS: Charts from an acute care inpatient child and adolescent psychiatric unit from 2012 to 2014 were reviewed. A paired samples t test was performed to look for significant differences in sleep time 24 hours prior to S&R versus average sleep times for the same patients during hospitalization. RESULTS: A total of 232 S&R events occurred between 2012 and 2014. Of the incidents, 172 involved children who were ≤ 12 years old, and 178 incidents involved male patients. A paired sample t test revealed a significant mean (SD) decrease in sleep time prior to S&R (9.5 [2.24]) compared to average sleep time during hospitalization (10.07 [1.08], t205 = -3.722, P < .01). CONCLUSIONS: The study results reveal a statistically significant reduction in sleep time 24 hours prior to an S&R event compared to average sleep duration during hospitalization. The association between sleep times and subsequent problem behaviors in an inpatient setting require further evaluation.

Effect of cognitive behavioural therapy on sleep and opioid medication use in adults with fibromyalgia and insomnia.

Sleep and opioid medications used to treat insomnia and chronic pain are associated with adverse side effects (falls and cognitive disturbance). Although behavioural treatments such as cognitive behavioral therapy for insomnia (CBT-I) and pain (CBT-P) improve sleep and clinical pain, their effects on sleep and opioid medication use are unclear. In this secondary analysis of published trial data, we investigated whether CBT-I and CBT-P reduced reliance on sleep/opioid medication in patients with fibromyalgia and insomnia (FMI). Patients with FMI (n = 113, Mage  = 53.0, SD = 10.9) completed 8 weeks of CBT-I (n = 39), CBT-P (n = 37) or waitlist control (WLC; n = 37). Participants completed 14 daily diaries at baseline, post-treatment and 6-month follow-up, assessing sleep and opioid medication usage. Multilevel modelling examined group by time effects on days of medication use. A significant interaction revealed CBT-P reduced the number of days of sleep medication use at post-treatment, but usage returned to baseline levels at follow-up. There were no other significant within- or between-group effects. CBT-P led to immediate reductions in sleep medication usage, despite lack of explicit content regarding sleep medication. CBT-I and CBT-P may be ineffective as stand-alone treatments for altering opioid use in FMI. Future work should explore CBT as an adjunct to other behavioural techniques for opioid reduction.

Effects of stress on functional connectivity during problem solving.

AIM: Our purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect. METHODS: Forty-five healthy participants (Mean age: 19.6 â€‹± â€‹1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task. RESULTS: There was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene â€‹× â€‹stress interaction on solution latency was also observed. DISCUSSION: Results from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.

Effects of stress on functional connectivity during verbal processing.

Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.6 ± 1.6 years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.

Phosphodiesterase-2 inhibitor reverses corticosterone-induced neurotoxicity and related behavioural changes via cGMP/PKG dependent pathway.

Phosphodiesterase 2 (PDE2) is an enzyme responsible for hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to restrict intracellular signalling of these second messenger molecules. This study investigated how PDE2 inhibitor Bay 60-7550 affects the dysregulated glucocorticoid signalling in neuronal cells and regulates depressive behaviours after chronic stress in mice. We found that exposure of hippocampal neurons to corticosterone resulted in time- and concentration-dependent increases in PDE2 expression. These intriguing findings were confirmed in the hippocampal cell line HT-22. After corticosterone exposure for 24 h, HT-22 cells showed a concentration-dependent increase in mRNA levels for PDE2 subtypes, PDE2A1 and 2A3, as well as for the total PDE2A protein expression. Bay 60-7550 was found to reverse the cell lesion induced by corticosterone (50 µm). This neuroprotective effect was blocked by pretreatment with protein kinase G inhibitor KT5823, but not protein kinase A inhibitor H89, suggesting the involvement of cGMP-dependent signalling. Although Bay 60-7550 treatment for 24 h did not change the levels of phosphorylated mitogen-activated protein kinases ERK1/2 (pERK) and phosphorylated cAMP response element-binding protein (pCREB), it down-regulated pERK at 2 h and up-regulated a CREB co-activator, CREB-binding protein, at 24 h. Both of these effects were blocked by KT 5823. Furthermore, Bay 60-7550 reversed corticosterone-induced down-regulation of brain-derived neurotrophic factor protein levels 24 h after corticosterone exposure. In behavioural testing, Bay 60-7550 produced antidepressant-like effects and reduced corticosterone levels in stressed mice, further supporting the involvement of a PDE2-dependent pathway in mediating Bay 60-7550's effect during stress hormone insults.