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Loneliness is a highly prevalent experience in schizophrenia. Theoretical models developed in the general population propose that loneliness is tantamount to a feeling of being unsafe, is accompanied by enhanced environmental threat perception, and leads to poor physical, emotional, and cognitive functioning. Previous research has reported that loneliness is associated with poorer physical and emotional health in schizophrenia; however, few studies have directly compared loneliness and its correlates in persons with schizophrenia and non-psychiatric comparison subjects. The purpose of the current study was to evaluate similarities and differences in the construct of loneliness, the equivalency of the measurement of this construct, and similarities and differences in the pattern of external correlates of loneliness between schizophrenia and non-psychiatric comparison groups. The third version of the University of California, Los Angeles Loneliness Scale (UCLA-3) was administered to 116 individuals with schizophrenia or schizoaffective disorder and 106 non-psychiatric comparison subjects. Additional clinical and positive psychological measures were collected, as well as demographic characteristics of the two groups. Multiple groups confirmatory factor analysis revealed that the UCLA-3 was best characterized by a bifactor model in which all items loaded on a general loneliness dimension as well as one of two orthogonal method factors reflecting item wording in both groups. Furthermore, the UCLA-3 exhibited invariant measurement of these latent constructs across groups. Mean levels of loneliness were nearly a standard deviation higher in the schizophrenia group. Nonetheless, the overall pattern and strength of correlates were largely similar across groups, with loneliness being positively associated with depression, anxiety, and perceived stress, and negatively correlated with mental well-being, happiness, and resilience. Subtle differences in correlates of age, optimism, and satisfaction with life were found. Overall, loneliness appears to be distinct from other schizophrenia-related deficits and operates similarly across schizophrenia and NC groups, suggesting that theoretical models of loneliness developed in the general population may generalize to schizophrenia.

INTRODUCTION Despite their increased application, the heritability of Alzheimer's disease (AD)–related blood‐based biomarkers remains unexplored. METHODS Plasma amyloid beta 40 (Aβ40), Aβ42, the Aβ42/40 ratio, total tau (t‐tau), and neurofilament light (NfL) data came from 1035 men 60 to 73 years of age (μ = 67.0, SD = 2.6). Twin models were used to calculate heritability and the genetic and environmental correlations between them. RESULTS Additive genetics explained 44% to 52% of Aβ42, Aβ40, t‐tau, and NfL. The Aβ42/40 ratio was not heritable. Aβ40 and Aβ42 were genetically near identical (rg = 0.94). Both Aβ40 and Aβ42 were genetically correlated with NfL (rg = 0.35 to 0.38), but genetically unrelated to t‐tau. DISCUSSION Except for Aβ42/40, plasma biomarkers are heritable. Aβ40 and Aβ42 share mostly the same genetic influences, whereas genetic influences on plasma t‐tau and NfL are largely unique in early old‐age men. The absence of genetic associations between the Aβs and t‐tau is not consistent with the amyloid cascade hypothesis.

BackgroundCannabinoid-containing products are marketed to athletes as promoting recovery, in spite of a lack of data on their safety and effects. This randomized, double-blind, placebo-controlled, repeated-dose pilot study tested the safety, tolerability, and preliminary effects on recovery of a formulation containing cannabidiol (CBD; 35 mg), cannabigerol (CBG; 50 mg), beta caryophyllene (BCP; 25 mg), branched-chain amino acids (BCAAs; 3.8 g), and magnesium citrate (420 mg).MethodsExercise-trained individuals (N = 40) underwent an experimental induction of delayed onset muscle soreness (DOMS) and completed follow-up visits 24-, 48-, and 72-hours post-DOMS. Participants were randomized to active or placebo formulation, and consumed the formulation twice per day for 3.5 days.ResultsThere was one adverse event (AE) in the active group (diarrhea) and two AEs in placebo (dry mouth; eye rash/swollen eye). There was 100% self-reported compliance with formulation consumption across the two groups. For the primary outcome of interest, the estimate of effect for ratings of average soreness/discomfort 72 hours post-DOMS between active and placebo groups was −1.33 (85% confidence interval = -2.55, −0.10), suggesting moderate evidence of a treatment difference. The estimate of effect for the outcome of ratings of interference of soreness, discomfort, or stiffness on daily activities at work or home 48 hours post-DOMS was −1.82 (95% confidence interval = -3.64, −0.01), indicating a treatment difference of potential clinical importance. There was no significant effect between active and placebo groups on objective measures of recovery, sleep quality, or mood disturbance.ConclusionsThe tested formulation reduced interference of DOMS on daily activities, demonstrating its improvement on a functional aspect of recovery.

Background. Recent studies recommend medicinal cannabis (MC) as a potential treatment for chronic pain (CP) when conventional therapies are not successful; however, data from Australia is limited. This real-world evidence study explored how the introduction of MC related to concomitant medication use over time. Long-term safety also was examined. Methods. Data were collected by the Emerald Clinics (a network of seven clinics located across Australia) as part of routine practice from Jan 2020 toJan 2021. Medications were classified by group: antidepressants, benzodiazepines, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and total number of medications. Adverse events (AEs) were collected at each visit and subsequently coded using the Medical Dictionary for Regulatory Activities version 23 into the system organ class (SOC) and preferred term (PT). A total of 535 patients were analyzed. Results. The most common daily oral dose was 10 mg for delta-9-tetrahydrocannabinol (THC) and 15 mg for cannabidiol (CBD). With the introduction of MC, patients’ total number of medications consumed decreased over the course of one year; significant reductions in NSAIDs, benzodiazepines, and antidepressants were observed (p < .001). However, the number of prescribed opioid medications did not differ from baseline to the end of one year (p = .49). Only 6% of patients discontinued MC treatment during the study. A total of 600 AEs were reported in 310 patients during the reporting period and 97% of them were classified as nonserious. Discussion. Though observational in nature, these findings suggest MC is generally well-tolerated, consistent with the previous literature, and may reduce concomitant use of some medications. Due to study limitations, concomitant medication reductions cannot be causally attributed to MC. Nevertheless, these data underscore early signals that warrant further exploration in randomized trials.

Background Use of medical cannabis is increasing among older adults. However, few investigations have examined cannabis use in this population. Methods We assessed the authorization patterns, safety, and effects of medical cannabis in a sub-analysis of 201 older adults (aged ≥ 65 years) who completed a 3-month follow-up during this observational study of patients who were legally authorized a medical cannabis product ( N = 67). Cannabis authorization patterns, adverse events (AEs), Edmonton Symptom Assessment Scale-revised (ESAS-r), and Brief Pain Inventory Short Form (BPI-SF) data were collected. Results The most common symptoms for which medical cannabis was authorized were pain (159, 85.0%) and insomnia (9, 4.8%). At baseline and at the 3-month follow-up, cannabidiol (CBD)-dominant products were authorized most frequently (99, 54%), followed by balanced products (76, 42%), and then delta-9-tetrahydrocannabinol (THC)-dominant products (8, 4.4%). The most frequent AEs were dizziness (18.2%), nausea (9.1%), dry mouth (9.1%), and tinnitus (9.1%). Significant reductions in ESAS-r scores were observed over time in the domains of drowsiness ( p = .013) and tiredness ( p = .031), but not pain ( p = .106) or well-being ( p = .274). Significant reductions in BPI-SF scores over time were observed for worst pain ( p = .010), average pain ( p = .012), and overall pain severity ( p = 0.009), but not pain right now ( p = .052 ) or least pain ( p = .141). Conclusions Overall, results suggest medical cannabis was safe, well-tolerated, and associated with clinically meaningful reductions in pain in this sample of older adults. However, the potential bias introduced by the high subject attrition rate means that all findings should be interpreted cautiously and confirmed by more rigorous studies.

Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems. The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse ('baseline') and the longitudinal Vietnam Era Twin Study of Aging ('follow-up'). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)]. Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07-1.57), erectile dysfunction (OR 1.32, 95% CI 1.10-1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04-1.53), and sleep apnea (OR 1.40, 95% CI 1.13-1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09-1.60). A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.

Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance. Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass). Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition. Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.

Introduction Practice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how accounting for PEs using a replacement‐participants method impacts incident MCI diagnosis. Methods Of 889 baseline cognitively normal (CN) Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 722 returned 1 year later (mean age = 74.9 ± 6.8 at baseline). The scores of test‐naïve demographically matched “replacement” participants who took tests for the first time were compared to returnee scores at follow‐up. PEs—calculated as the difference between returnee follow‐up scores and replacement participants scores—were subtracted from follow‐up scores of returnees. PE‐adjusted cognitive scores were then used to determine if individuals were below the impairment threshold for MCI. Cerebrospinal fluid amyloid beta, phosphorylated tau, and total tau were used for criterion validation. In addition, based on screening and recruitment numbers from a clinical trial of amyloid‐positive individuals, we estimated the effect of earlier detection of MCI by accounting for cognitive PEs on a hypothetical clinical trial in which the key outcome was progression to MCI. Results In the ADNI sample, PE‐adjusted scores increased MCI incidence by 19% (P < .001), increased proportion of amyloid‐positive MCI cases (+12%), and reduced proportion of amyloid‐positive CNs (–5%; P’s < .04). Additional calculations showed that the earlier detection and increased MCI incidence would also substantially reduce necessary sample size and study duration for a clinical trial of progression to MCI. Cost savings were estimated at ≈$5.41 million. Discussion Detecting MCI as early as possible is of obvious importance. Accounting for cognitive PEs with the replacement‐participants method leads to earlier detection of MCI, improved diagnostic accuracy, and can lead to multi‐million‐dollar cost reductions for clinical trials.

Introduction  Our goal was to determine whether cognitive and cerebrospinal fluid (CSF) markers of tau and amyloid beta 1‐42 (Aβ42) differ between Vietnam‐era veterans with and without history of traumatic brain injury (TBI) and whether TBI moderates the association between CSF markers and neurocognitive functioning. Methods  A total of 102 male participants (52 TBI, 50 military controls [MCs]; mean age = 68) were included. Levels of CSF Aβ42, tau phosphorylated at the threonine 181 position (p‐tau), and total tau (t‐tau) were quantified. Group differences in CSF markers and cognition as well as the moderating effect of TBI on CSF and cognition associations were explored. Results  Relative to MCs, the TBI group showed significantly higher p‐tau (P = .01) and t‐tau (P = .02), but no differences in amyloid (P = .09). TBI history moderated the association between CSF tau and performance on a measure of processing speed (t‐tau: P  = .04; p‐tau: P  = .02). Discussion  Tau accumulation may represent a mechanism of dementia risk in older veterans with remote TBI.