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Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

Background Grip strength is an indicator of physical function with potential predictive value for health in ageing populations. We assessed whether trends in grip strength from midlife predicted later-life brain health and cognition. Methods 446 participants in an ongoing British birth cohort study, the National Survey of Health and Development (NSHD), had their maximum grip strength measured at ages 53, 60–64, and 69, and subsequently underwent neuroimaging as part of a neuroscience sub-study, referred to as “Insight 46”, at age 69–71. A group-based trajectory model identified latent groups of individuals in the whole NSHD cohort with below- or above-average grip strength over time, plus a reference group. Group assignment, plus standardised grip strength levels and change from midlife were each related to measures of whole-brain volume (WBV) and white matter hyperintensity volume (WMHV), plus several cognitive tests. Models were adjusted for sex, body size, head size (where appropriate), sociodemographics, and behavioural and vascular risk factors. Results Lower grip strength from midlife was associated with smaller WBV and lower matrix reasoning scores at age 69–71, with findings consistent between analysis of individual time points and analysis of trajectory groups. There was little evidence of an association between grip strength and other cognitive test scores. Although greater declines in grip strength showed a weak association with higher WMHV at age 69–71, trends in the opposite direction were seen at individual time points with higher grip strength at ages 60–64, and 69 associated with higher WMHV. Conclusions This study provides preliminary evidence that maximum grip strength may have value in predicting brain health. Future work should assess to what extent age-related declines in grip strength from midlife reflect concurrent changes in brain structure.

Aberrations to metacognition—the ability to reflect on and evaluate self-performance—are a feature of poor mental health. Theoretical models of post-traumatic stress disorder propose that following severe stress or trauma, maladaptive metacognitive evaluations and appraisals of the event drive the development of symptoms. Empirical research is required in order to reveal whether disruptions to metacognition cause or contribute to symptom development in line with theoretical accounts, or are simply a consequence of ongoing psychopathology. In two experiments, using hierarchical Bayesian modelling of metacognition measured in a memory recognition task, we assessed whether distortions to metacognition occur at a state-level after an acute stress induction, and/or at a trait-level in a sample of individuals experiencing intrusive memories following traumatic stress. Results from experiment 1, an in-person laboratory-based experiment, demonstrated that heightened psychological responses to the stress induction were associated with poorer metacognitive efficiency, despite there being no overall change in metacognitive efficiency from pre- to post-stress ( N  = 27). Conversely, in experiment 2, an online experiment using the same metamemory task, we did not find evidence of metacognitive alterations in a transdiagnostic sample of patients with intrusive memory symptomatology following traumatic stress ( N  = 36, compared to 44 matched controls). Our results indicate a relationship between state-level psychological responses to stress and metacognitive alterations. The lack of evidence for pre- to post-stress differences in metamemory illustrates the importance for future studies to reveal the direction of this relationship, and consequently the duration of stress-associated metacognitive impairments and their impact on mental health.

BackgroundMindfulness-based programmes (MBPs) are increasingly offered at work, often in online self-guided format. However, the evidence on MBPs’ effect on work performance (WP) is inconsistent.ObjectiveThis pragmatic randomised controlled feasibility trial assessed procedural uncertainties, intervention acceptability and preliminary effect sizes of an MBP on WP, relative to an alternative intervention.Methods241 employees from eight employers were randomised (1:1) to complete a 4-week, self-guided, online MBP or a light physical exercise programme (LE)(active control). Feasibility and acceptability measures were of primary interest. WP at postintervention (PostInt) was the primary outcome for preliminary assessment of effect sizes. Secondary outcomes assessed mental health (MH) and cognitive processes hypothesised to be targeted by the MBP. Outcomes were collected at baseline, PostInt and 12-week follow-up (12wFUP). Prospective trial protocol: NCT04631302.Findings87% of randomised participants started the course. Courses had high acceptability. Retention rates were typical for online trials (64% PostInt; 30% 12wFUP). MBP, compared with the LE control, offered negligible benefits for WP (PostInt (d=0.06, 95% CI −0.19 to 0.32); 12wFUP (d=0.02, 95% CI −0.30 to 0.26)). Both interventions improved MH outcomes (ds=−0.40 to 0.58, 95% CI −0.32 to 0.18); between-group differences were small (ds=−0.09 to 0.04, 95% CI −0.15 to 0.17).ConclusionThe trial is feasible; interventions are acceptable. Results provide little support for a later phase trial comparing an MBP to a light exercise control. To inform future trials, we summarise procedural challenges.Clinical implicationsResults suggest MBPs are unlikely to improve WP relative to light physical exercise. Although the MBP improved MH, other active interventions may be just as efficacious.Trial registration numberNCT04631302.

There is emerging evidence that the live herpes zoster (shingles) vaccine might protect against dementia. However, the existing data are limited and refer only to the live vaccine, which is now discontinued in the United States and many other countries in favor of a recombinant vaccine. Whether the recombinant shingles vaccine protects against dementia remains unknown. Here we used a natural experiment opportunity created by the rapid transition from the use of live to the use of recombinant vaccines to compare the risk of dementia between vaccine types. We show that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected. The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus–diphtheria–pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomized control trial to confirm the possible additional benefit of the recombinant shingles vaccine. A natural experiment including more than 200,000 people who received a shingles vaccine reveals that, within 6 years of vaccination, the recombinant vaccine is associated with lower risk of dementia than is the live vaccine.

Emotion can affect the way in which experiences are stored in our memory. The dual representation account proposes that traumatic events may be encoded as fragmented sensory-perceptual details without a broader conceptual organisation. This can result in involuntary retrieval of perceptual information triggered by environmental cues without the associated context – a phenomenon referred to as intrusive memories.Currently, it is unknown whether individuals who experience intrusive memories have an underlying vulnerability to aberrant memory encoding, which may lead to the onset or maintenance of symptoms.In Experiment 1, we examined memory recall for neutral and negative images in a transdiagnostic sample of patients with intrusive memories (N = 36), compared to healthy controls (N = 44). Clinical diagnoses in the patient sample included Post-Traumatic Stress Disorder, Major Depressive Disorder, Social Anxiety Disorder, Generalised Anxiety Disorder, Panic Disorder and Other Specified Feeding or Eating Disorders. We excluded participants currently taking psychotropic medication. At encoding, participants viewed neutral, negative and mixed valence image pairs. In the test phase, participants were presented with cues and, if recognised, were asked to recall the associated image. We found a significant group effect, with patients demonstrating impaired item memory for negative images [F(1,280) = 4.435, p = 0.036], relative to healthy controls. This group difference might suggest that individuals with intrusive memories experienced greater sensitivity to negative stimuli, leading to disruptions in memory encoding. Recent work highlights attention maintenance on threat and high levels of threat-related emotional arousal in anxiety- and fear-related disorders which may be one factor driving the disruption to item memory observed in our clinical population.For Experiment 2, in a separate sample of healthy participants (N = 18) we measured eye-tracking behaviour during the encoding phase of the same task. Healthy participants showed greater item memory [F(3, 136 = 2.893, p = 0.0377] and avoidance of fixation [F(1, 110) = 4.898, p = 0.029] on highly arousing, negative stimuli relative to neutral. This might suggest that a shift in attention away from negative stimuli prevents item memory impairments for emotional information.Our future work will identify biological factors driving attentional biases and higher emotional arousal in clinical populations.

Cognitive distancing is an emotion regulation strategy commonly used in psychological treatment of various mental health disorders, but its therapeutic mechanisms are unknown. 935 participants completed an online reinforcement learning task involving choices between pairs of symbols with differing reward contingencies. Half (49.1%) of the sample was randomised to a cognitive self-distancing intervention and were trained to regulate or 'take a step back' from their emotional response to feedback throughout. Established computational ( -learning) models were then fit to individuals' choices to derive reinforcement learning parameters capturing clarity of choice values (inverse temperature) and their sensitivity to positive and negative feedback (learning rates). Cognitive distancing improved task performance, including when participants were later tested on novel combinations of symbols without feedback. Group differences in computational model-derived parameters revealed that cognitive distancing resulted in clearer representations of option values (estimated 0.17 higher inverse temperatures). Simultaneously, distancing caused increased sensitivity to negative feedback (estimated 19% higher loss learning rates). Exploratory analyses suggested this resulted from an evolving shift in strategy by distanced participants: initially, choices were more determined by expected value differences between symbols, but as the task progressed, they became more sensitive to negative feedback, with evidence for a difference strongest by the end of training. Adaptive effects on the computations that underlie learning from reward and loss may explain the therapeutic benefits of cognitive distancing. Over time and with practice, cognitive distancing may improve symptoms of mental health disorders by promoting more effective engagement with negative information.

At least half of all patients with mental health disorders do not respond adequately to psychological therapy. Acutely enhancing particular biological or psychological processes during psychological therapy may improve treatment outcomes. However, previous studies are confined to specific augmentation approaches, typically assessed within single diagnostic categories. Our objective was to assess to what degree acute augmentations of psychological therapy reduce psychiatric symptoms and estimate effect sizes of augmentation types (for example, brain stimulation or psychedelics). We searched Medline, PsycINFO and Embase for controlled studies published between database inception and 25 May 2022. We conducted a preregistered random-effects meta-analysis (PROSPERO CRD42021236403). We identified 108 studies ( N  = 5,889). Acute augmentation significantly reduced the severity of mental health problems (Hedges’ g  = −0.27, 95% CI: [−0.36, −0.18]; P  < 0.0001), particularly for the transdiagnostic dimensions 'Fear' and 'Distress'. This result survived a trim-and-fill analysis to account for publication bias. Subgroup analyses revealed that pharmacological, psychological and somatic augmentations were effective, but to varying degrees. Acute augmentation approaches are a promising route to improve outcomes from psychological therapy.

Importance: To support treatment assignment, mechanistic biomarkers should be selectively sensitive to specific interventions. Here, we examine whether different components of reinforcement learning in humans satisfy this necessary precondition. We focus on pharmacological manipulations of dopamine and serotonin that form the backbone of first-line management of common mental illnesses such as depression and anxiety. Objective: To perform a meta-analysis of pharmacological manipulations of dopamine and serotonin and examine whether they show distinct associations with reinforcement learning components in humans. Data Sources: Ovid MEDLINE/PubMed, Embase, and PsycInfo databases were searched for studies published between January 1, 1946 and January 19, 2023 (repeated April 9, 2024, and October 15, 2024) investigating dopaminergic or serotonergic effects on reward/punishment processes in humans, according to PRISMA guidelines. Study Selection: Studies reporting randomized, placebo-controlled, dopaminergic or serotonergic manipulations on a behavioral outcome from a reward/punishment processing task in healthy humans were included. Data Extraction and Synthesis: Standardized mean difference (SMD) scores were calculated for the comparison between each drug (dopamine/serotonin) and placebo on a behavioral reward or punishment outcome and quantified in random-effects models for overall reward/punishment processes and four main subcategories. Study quality (Cochrane Collaboration's tool), moderators, heterogeneity, and publication bias were also assessed. Main Outcome(s) and Measure(s): Performance on reward/punishment processing tasks. Results: In total, 68 dopamine and 39 serotonin studies in healthy volunteers were included (Ndopamine=2291, Nplacebo=2284; Nserotonin=1491, Nplacebo=1523). Dopamine was associated with an increase in overall reward (SMD=0.18, 95%CI [0.09 0.28]) but not punishment function (SMD=-0.06, 95%CI [-0.26,0.13]). Serotonin was not meaningfully associated with overall punishment (SMD=0.22, 95%CI [-0.04,0.49]) or reward (SMD=0.02, 95%CI [-0.33,0.36]). Importantly, dopaminergic and serotonergic manipulations had distinct associations with subcomponents. Dopamine was associated with reward learning/sensitivity (SMD=0.26, 95%CI [0.11,0.40]), reward discounting (SMD=-0.08, 95%CI [-0.14,-0.01]) and reward vigor (SMD=0.32, 95%CI [0.11,0.54]). By contrast, serotonin was associated with punishment learning/sensitivity (SMD=0.32, 95%CI [0.05,0.59]), reward discounting (SMD=-0.35, 95%CI [-0.67,-0.02]), and aversive Pavlovian processes (within-subject studies only; SMD=0.36, 95%CI [0.20,0.53]). Conclusions and Relevance: Pharmacological manipulations of both dopamine and serotonin have measurable associations with reinforcement learning in humans. The selective associations with different components suggests that reinforcement learning tasks could form the basis of selective, mechanistically interpretable biomarkers to support treatment assignment.Competing Interest StatementQJMH has received fees and options for consultancies for Aya Technologies and Alto Neuroscience. MB has received consulting fees from J&J, Engrail Therapeutics, CHDR, and travel expenses from Lundbeck. He was previously employed by P1vital Ltd.Footnotes* fixed minor errors and revised language and uploading higher resolution figures.