publications
2024
- Maxime Taquet, Quentin Dercon, John A. Todd, and Paul J. Harrison
There is emerging evidence that the live herpes zoster (shingles) vaccine might protect against dementia. However, the existing data are limited, and only refer to the live vaccine now discontinued in the USA and many other countries in favour 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 vaccines. 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 compared to two other vaccines commonly used in older people: influenza and tetanus/diphtheria/pertussis vaccines. The effect was robust across multiple secondary analyses, and present in both men and women but greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomised control trial to confirm the possible additional benefit of the recombinant shingles vaccine.
- Alicia J. Smith, James A. Bisby, Quentin Dercon, Anna Bevan, Stacey L. Kigar, Mary-Ellen Lynall, Tim Dalgleish, Caitlin Hitchcock, and Camilla L. Nord
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.
- Maris Vainre, Tim Dalgleish, Peter Watson, Christina Haag, Quentin Dercon, Julieta Galante, and Caitlin Hitchcock
Background: Mindfulness-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.
Objective: This pragmatic randomised controlled feasibility trial assessed procedural uncertainties, intervention acceptability and preliminary effect sizes of an MBP on WP, relative to an alternative intervention.
Methods: 241 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.
Findings: 87% 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).
Conclusion: The 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 implications: Results 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 number: NCT04631302.
2023
- Camilla L. Nord, Beth Longley, Quentin Dercon, Veronica Phillips, Julia Funk, Siobhan Gormley, Rachel Knight, Alicia J. Smith, and Tim Dalgleish
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.
- Quentin Dercon†, Sara Z. Mehrhof†, Timothy R. Sandhu, Caitlin Hitchcock, Rebecca P. Lawson, Diego A. Pizzagalli, Tim Dalgleish, and Camilla L. Nord
Psychological therapy is an effective treatment for many mental health disorders, but its therapeutic mechanisms are relatively unclear. We investigated whether therapy may affect aspects of learning from rewards and losses, by comparing the performance on a learning task of participants who were asked to try to ’distance’ themselves from task feedback, to that of participants not engaging in so-called ’cognitive distancing’.
Participants engaging in cognitive distancing performed slightly better on the task. Using computational modelling, we found evidence that distancing led to choosing more driven by differences in expected values (i.e., the expected future return of a given option), and adaptive changes in how losses were used to compute and update these expected values. Our results indicate that distancing may improve symptoms of mental health disorders by promoting more effective engagement with negative information.
All analyses were implemented in a custom R package, pstpipeline, and each step is laid out in accompanying Jupyter notebooks alongside methodological motivations.
Background: Cognitive distancing is an emotion regulation strategy commonly used in psychological treatment of various mental health disorders, but its therapeutic mechanisms are unknown.
Methods: 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 (Q-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).
Results: 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.
Conclusions: 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.
2022
- Maxime Taquet, Rebecca Sillett, Lena Zhu, Jacob Mendel, Isabella Camplisson, Quentin Dercon, and Paul J. Harrison
Background: COVID-19 is associated with increased risks of neurological and psychiatric sequelae in the weeks and months thereafter. How long these risks remain, whether they affect children and adults similarly, and whether SARS-CoV-2 variants differ in their risk profiles remains unclear.
Methods: In this analysis of 2-year retrospective cohort studies, we extracted data from the TriNetX electronic health records network, an international network of de-identified data from health-care records of approximately 89 million patients collected from hospital, primary care, and specialist providers (mostly from the USA, but also from Australia, the UK, Spain, Bulgaria, India, Malaysia, and Taiwan). A cohort of patients of any age with COVID-19 diagnosed between Jan 20, 2020, and April 13, 2022, was identified and propensity-score matched (1:1) to a contemporaneous cohort of patients with any other respiratory infection. Matching was done on the basis of demographic factors, risk factors for COVID-19 and severe COVID-19 illness, and vaccination status. Analyses were stratified by age group (age \textless18 years [children], 18–64 years [adults], and ≥65 years [older adults]) and date of diagnosis. We assessed the risks of 14 neurological and psychiatric diagnoses after SARS-CoV-2 infection and compared these risks with the matched comparator cohort. The 2-year risk trajectories were represented by time-varying hazard ratios (HRs) and summarised using the 6-month constant HRs (representing the risks in the earlier phase of follow-up, which have not yet been well characterised in children), the risk horizon for each outcome (ie, the time at which the HR returns to 1), and the time to equal incidence in the two cohorts. We also estimated how many people died after a neurological or psychiatric diagnosis during follow-up in each age group. Finally, we compared matched cohorts of patients diagnosed with COVID-19 directly before and after the emergence of the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529) variants.
Findings: We identified 1 487 712 patients with a recorded diagnosis of COVID-19 during the study period, of whom 1 284 437 (185 748 children, 856 588 adults, and 242 101 older adults; overall mean age 42·5 years [SD 21·9]; 741 806 [57·8%] were female and 542 192 [42·2%] were male) were adequately matched with an equal number of patients with another respiratory infection. The risk trajectories of outcomes after SARS-CoV-2 infection in the whole cohort differed substantially. While most outcomes had HRs significantly greater than 1 after 6 months (with the exception of encephalitis; Guillain-Barré syndrome; nerve, nerve root, and plexus disorder; and parkinsonism), their risk horizons and time to equal incidence varied greatly. Risks of the common psychiatric disorders returned to baseline after 1–2 months (mood disorders at 43 days, anxiety disorders at 58 days) and subsequently reached an equal overall incidence to the matched comparison group (mood disorders at 457 days, anxiety disorders at 417 days). By contrast, risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period. Post-COVID-19 risk trajectories differed in children compared with adults: in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02 [95% CI 0·94–1·10) or anxiety (1·00 [0·94–1·06]) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 [1·09–1·33] to 2·16 [1·46–3·19]). Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days). A sizeable proportion of older adults who received a neurological or psychiatric diagnosis, in either cohort, subsequently died, especially those diagnosed with dementia or epilepsy or seizures. Risk profiles were similar just before versus just after the emergence of the alpha variant (n=47 675 in each cohort). Just after (vs just before) the emergence of the delta variant (n=44 835 in each cohort), increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate. With omicron (n=39 845 in each cohort), there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar.
Interpretation: This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them.
- Maxime Taquet, Quentin Dercon, and Paul J. Harrison
Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021, i.e. before the emergence of the Omicron variant). Associations with the number of vaccine doses (1 vs. 2) and age (\textless60 vs. ≥ 60 years-old) were assessed. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70–0.83, Bonferroni-corrected p \textless 0.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those \textless60 years-old, whereas no robust associations were observed in those ≥60 years-old. In summary, COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae.
2021
- Maxime Taquet, Quentin Dercon, Sierra Luciano, John R. Geddes, Masud Husain, and Paul J. Harrison
Background: 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.
Methods and Findings: 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. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.
Conclusions: 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.
- Quentin Dercon, Jennifer M. Nicholas, Sarah-Naomi James, Jonathan M. Schott, and Marcus Richards
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.
- Jordi Quoidbach, Quentin Dercon, Maxime Taquet, Martin Desseilles, Yves Alexandre Montjoye, and James J. Gross
