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We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.

Identifying those who are most (and least) likely to benefit from a stepped-care approach to cognitive behavioral therapy for insomnia (CBT-I) increases access to insomnia therapies while minimizing resource consumption. The present study investigates non-targeted factors in a single-session of CBT-I that may act as barriers to early response and remission. Participants (N = 303) received four sessions of CBT-I and completed measures of subjective insomnia severity, fatigue, sleep-related beliefs, treatment expectations, and sleep diaries. Subjective insomnia severity and sleep diaries were completed between each treatment session. Early response was defined as a 50% reduction in Insomnia Severity Index (ISI) scores and early remission was defined by < 10 on the ISI after the first session. A single-session of CBT-I significantly reduced subjective insomnia severity scores and diary total wake time. Logistic regression models indicated that lower baseline fatigue was associated with increased odds of early remission (B = −.05, p =.02), and lower subjective insomnia severity (B = −.13, p =.049). Only fatigue was a significant predictor of early treatment response (B = −.06, p =.003) Fatigue appeared to be an important construct that dictates early changes in perceived insomnia severity. Beliefs about the relationship between sleep and daytime performance may hinder perceived improvements in insomnia symptoms. Incorporating fatigue management strategies and psychoeducation about the relationship between sleep and fatigue may target non-early responders. Future research would benefit from further profiling potential early insomnia responders/remitters. [ABSTRACT FROM AUTHOR]

Insomnia is frequently reported by women during menopause due to physiological changes and environmental factors and is associated with negative daytime sequelae. Due to medication side effects and patient preferences, there is increased interest in the use of psychological treatments for menopausal insomnia. The primary objective of this review is to review the efficacy of cognitive-behavioral, behavioral, and mindfulness-based (CBBMB) therapies in treating insomnia in peri- and post-menopausal women. The secondary objective is to review the effect of CBBMB therapies on relevant secondary outcomes to gain a comprehensive understanding of their impacts. We conducted a narrative review of the literature. A search of PubMed and Google Scholar was conducted between January 2020 and March 2021. Cognitive-behavioral therapy (CBT) for insomnia is efficacious, with corollary improvements in mood, functional outcomes and potential mechanistic factors (e.g., unhelpful beliefs). Sleep restriction therapy is also efficacious, with somewhat poorer effects on secondary outcomes relative to CBT. Mindfulness meditation and relaxation for insomnia demonstrated promise, but its long-term effects remain unknown. Research with more diverse samples and head-to-head comparisons is needed. Dissemination of CBBMBs for insomnia in clinics where menopausal women seek care is an important next step. [ABSTRACT FROM AUTHOR]

Providers of Cognitive-Behavioral Therapy for Insomnia (CBT-I) are often asked whether the behavioral recommendations (e.g., stimulus control, sleep restriction) must be adhered to ad infinitum. We examined whether changes in sleep habits/behaviors are a life sentence, or whether patients who remit can relax their adherence while maintaining their treatment gains at 1-year follow-up (FU). Participants (N = 179) completed 2 weeks of sleep diaries and measures of insomnia severity and safety behaviors at baseline and following four sessions of CBT-I. Of the 137 patients that achieved remission, 77 completed these measures at 1-year FU. Improvements in insomnia severity and total wake time (TWT) at post-treatment were maintained at FU (ps ≥.52). Similarly, reductions in safety behaviors were maintained at FU (p – 1.00), whereas lingering in bed reduced during treatment (p <.001) but increased at FU (p <.001). Changes in sleep habits after treatment did not predict insomnia severity at FU. However, increases in time in bed positively predicted TWT at FU (p =.001). Those who remit after CBT-I may generally relax their adherence to behavioral recommendations without significantly impacting their perceived insomnia symptoms 1 year after treatment despite some increases in TWT. Results increase our confidence in CBT-I as a brief and durable intervention. [ABSTRACT FROM AUTHOR]

Background: Convergent evidence implicates gut microbiota in human health and disease. Hitherto, relatively few studies have evaluated the gut microbiota profile in individuals with bipolar disorder (BD) relative to healthy controls (HC). Methods: Fecal samples were collected from subjects (aged 18–65) meeting DSM-5-defined criteria for BD and age- and sex-matched HC without current or past history of mental or major medical disorders. Samples were sequenced using Illumina sequencing and association of specific taxa and co-occurrence of taxa with sample groups including the effect of diet was assessed using cluster analysis and analysis of communities of microorganisms (ANCOM). Nutritional composition was evaluated using the Dietary Questionnaire for Epidemiological Studies (DQES v2) Food Frequency Questionnaire. Results: Forty-six subjects were enrolled (n=23 BD, n=23 HC). Cluster analyses did not identify any significant differences between BD and HC (p=0.38). Lower microbiota diversity was observed among BD subjects relative to HC (p=0.04). A greater abundance of a Clostridiaceae OTU was observed among BD subjects when compared to HC and of Collinsella among BD-II subjects relative to BD-I. Cluster analysis revealed that neither diagnosis (p=0.38) nor diet (p=0.43) had a significant effect on overall gut microbiota composition. Limitations: This study has a small sample size and insufficient control for some potential moderating factors (e.g. psychotropic medication and smoking). Conclusion: This study suggests that individuals with BD may have a distinct gut microbiota profile compared to healthy controls, with a greater abundance of Clostridiaceae and Collinsella. These findings need to be replicated in future studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Individuals with binge eating disorder (BED) are differentially affected by attention-deficit/hyperactivity disorder (ADHD), obesity, and substance use disorder. We have investigated to what extent cognitive deficits are relevant to binge eating behavior (BEB). METHODS: Data from the International Mood Disorders Collaborative Project were retrospectively and cross-sectionaOy analyzed to compare individuals with and without BEB on measures of anhedonia and general cognitive functions (n = 566). BEB was assessed using items from the Mini International Neuropsychiatric Interview Plus 5.0.0 for DSM-IV-TR that correspond with DSM-5-defined diagnostic criteria for BED. Individuals currently prescribed benzodiazepines were excluded from analyses. RESULTS: Individuals with BEB were more likely to exhibit anhedonia (P = .044) and general cognitive (P = .005) symptoms, when compared to those without BEB. We also observed that individuals with BEB were more likely to have specific psychiatric (eg, ADHD) and medical (eg, obesity) disorders (P < .05). CONCLUSIONS: Our results suggest that a central disturbance in cognitive processes may be mechanistically relevant to the cause and treatment of BEB in adults. [ABSTRACT FROM AUTHOR]

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with deficits across multiple cognitive domains; however, the determinants of cognitive impairment in T2DM are not well characterized. We aimed to evaluate body mass index (BMI), glycemic control, and T2DM duration as moderators of cognitive dysfunction in T2DM. METHODS: We conducted a meta-analytic review of the literature reporting data on BMI, hemoglobin A]c(HbAlc), T2DM duration, and validated measures of processing speed (ie, Digit Symbol Substitution Test, Trail Making Test [TMT]-A), verbal learning and memory (ie, Rey Auditory Verbal Learning Test), and working memory/executive function (ie, TMT-B) among individuals with vs without T2DM. RESULTS: Individuals with T2DM demonstrated deficits across multiple cognitive domains (k = 40; n = 4,252 T2DM; n = 22,322 non-T2DM; effect sizes 0.21 to 0.35). Illness duration and BMI did not significantly moderate measures of cognition; however, higher HbAlc levels were significantly associated with deficits in measures of processing speed (R² values 0.41 to 0.73, P < .01) and working memory/executive function (R² = 0.62, P<. 001). CONCLUSIONS: Adults with T2DM exhibited significant deficits across multiple domains of cognitive function. Additionally, we identified an association between poorer glycemic control and cognitive dysfunction. A clinical translation of our findings relates to the reduction in morbidity by improving glycemic control. [ABSTRACT FROM AUTHOR]

Sleep disturbance is frequently reported by women during the menopausal transition due to various physiological changes and environmental factors. Insomnia is a critical treatment target for its deleterious effects on daytime functioning and quality of life and increased risk of developing a depressive disorder. Due to medication side effects and patient preferences, there is increased interest in the use of psychological treatments that address the myriad of menopausal symptoms, including cognitive-behavioural therapy, clinical hypnosis and mindfulness-based therapies. The objective of this article is to review the effects of psychological treatments for menopausal symptoms on sleep disturbance in peri-/postmenopausal women. We conducted a systematic review of the literature using PubMed and reference lists from inception until May 2023, including 12 studies that evaluated sleep as a secondary outcome. Most studies found that group and self-help (guided and unguided) cognitive-behavioural therapies and clinical hypnosis for menopausal symptoms have positive effects on sleep among women with significant vasomotor symptoms. There was preliminary support for mindfulness-based stress reduction. Future research including more diverse samples and women with sleep disorders is needed. Evaluating the implementation of psychological therapies in clinics where menopausal women seek care is an important next step., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Type 2 diabetes mellitus (T2DM) is associated with deficits across multiple cognitive domains; however, the determinants of cognitive impairment in T2DM are not well characterized. We aimed to evaluate body mass index (BMI), glycemic control, and T2DM duration as moderators of cognitive dysfunction in T2DM., Methods: We conducted a meta-analytic review of the literature reporting data on BMI, hemoglobin A1c (HbA1c), T2DM duration, and validated measures of processing speed (ie, Digit Symbol Substitution Test, Trail Making Test [TMT]-A), verbal learning and memory (ie, Rey Auditory Verbal Learning Test), and working memory/executive function (ie, TMT-B) among individuals with vs without T2DM., Results: Individuals with T2DM demonstrated deficits across multiple cognitive domains (k = 40; n = 4,252 T2DM; n = 22,322 non-T2DM; effect sizes 0.21 to 0.35). Illness duration and BMI did not significantly moderate measures of cognition; however, higher HbA1c levels were significantly associated with deficits in measures of processing speed (R2 values 0.41 to 0.73, P < .01) and working memory/executive function (R2 = 0.62, P < .001)., Conclusions: Adults with T2DM exhibited significant deficits across multiple domains of cognitive function. Additionally, we identified an association between poorer glycemic control and cognitive dysfunction. A clinical translation of our findings relates to the reduction in morbidity by improving glycemic control.

Background: Individuals with binge eating disorder (BED) are differentially affected by attention-deficit/hyperactivity disorder (ADHD), obesity, and substance use disorder. We have investigated to what extent cognitive deficits are relevant to binge eating behavior (BEB)., Methods: Data from the International Mood Disorders Collaborative Project were retrospectively and cross-sectionally analyzed to compare individuals with and without BEB on measures of anhedonia and general cognitive functions (n = 566). BEB was assessed using items from the Mini International Neuropsychiatric Interview Plus 5.0.0 for DSM-IV-TR that correspond with DSM-5-defined diagnostic criteria for BED. Individuals currently prescribed benzodiazepines were excluded from analyses., Results: Individuals with BEB were more likely to exhibit anhedonia (P = .044) and general cognitive (P = .005) symptoms, when compared to those without BEB. We also observed that individuals with BEB were more likely to have specific psychiatric (eg, ADHD) and medical (eg, obesity) disorders (P < .05)., Conclusions: Our results suggest that a central disturbance in cognitive processes may be mechanistically relevant to the cause and treatment of BEB in adults.

Introduction: To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents., Areas Covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper., Expert Opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.

Background: Cognitive dysfunction is a core transdiagnostic domain of Major Depressive Disorder (MDD) and is a principal determinant of functional recovery. However, it has been insufficiently targeted within the current therapeutic framework for MDD., Objective: To highlight these unmet cognitive needs in MDD., Method: An article search was conducted using PubMed from inception to November 2016: Major Depressive Disorder (and/or variant) was cross-referenced with the following terms: antidepressants, augmentation, cognition, cognitive deficits, cognitive dysfunction, functional outcomes, mechanism of action, and treatment. Articles informed by observational studies, clinical trials, and review articles relevant to the discussion of cognition and cognitive impairment in MDD were included for review. Additional terms and citations previously not identified in the initial search were obtained from a manual review of article reference lists., Results: Cognitive deficits in MDD are replicable, non-specific, and clinically significant. Abnormalities in the domains of learning/memory, executive function, attention, concentration, and processing speed are consistently reported. Only two antidepressants (i.e., duloxetine and vortioxetine) have established procognitive effects utilizing rigorous methodology in MDD. Most antidepressants improve cognitive function(s), but the extent to which they directly exert pro-cognitive effects is not yet understood., Conclusion: Cognitive dysfunction in MDD is a principal determinant of patient-reported outcomes (e.g., psychosocial function). Healthcare providers are encouraged to screen for cognitive dysfunction in MDD and familiarize themselves with the efficacy profiles of antidepressants on disparate cognitive domains., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)