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Major Depressive Disorder (MDD) is a complex mental health condition characterized by a wide spectrum of symptoms. According to the Diagnostic Statistical Manual 5 (DSM-5) criteria, patients can present with up to 1,497 different symptom combinations, yet all receive the same MDD diagnosis. This diversity in symptom presentation poses a significant challenge to understanding the disorder in the wider population. Subtyping offers a way to unpick this phenotypic diversity and enable improved characterization of the disorder. According to reviews, MDD subtyping work to date has lacked consistency in results due to inadequate statistics, non-transparent reporting, or inappropriate sample choice. By addressing these limitations, the current study aims to extend past phenotypic subtyping studies in MDD.
Objectives
(1) To investigate phenotypic subtypes at baseline in a sample of people with MDD;
(2) To determine if subtypes are consistent between baseline 6- and 12-month follow-ups; and
(3) To examine how participants move between subtypes over time.
Methods
This was a secondary analysis of a one-year longitudinal observational cohort study. We collected data from individuals with a history of recurrent MDD in the United Kingdom, the Netherlands and Spain (N=619). The presence or absence of symptoms was tracked at three-month intervals through the Inventory of Depressive Symptomatology: Self-Report (IDS-SR) assessment. We used latent class and three-step latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined participants’ transitions over time.
Results
We identified a 4-class solution based on model fit and interpretability, including (Class 1) severe with appetite increase, (Class 2), severe with appetite decrease, (Class 3) moderate, and (Class 4) low severity. The classes mainly differed in terms of severity (the varying likelihood of symptom endorsement) and, for the two more severe classes, the type of neurovegetative symptoms reported (Figure 1). The four classes were stable over time (measurement invariant) and participants tended to remain in the same class over baseline and follow-up (Figure 2).
Image:
Image 2:
Conclusions
We identified four stable subtypes of depression, with individuals most likely to remain in their same class over 1-year follow-up. This suggests a chronic nature of depression, with (for example) individuals in severe classes more likely to remain in the same class throughout follow-up. Despite the vast heterogeneous symptom combinations possible in MDD, our results emphasize differences across severity rather than symptom type. This raises questions about the meaningfulness of these subtypes beyond established measures of depression severity. Implications of these findings and recommendations for future research are made.
Disclosure of Interest
C. Oetzmann Grant / Research support from: C.O. is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences., N. Cummins: None Declared, F. Lamers: None Declared, F. Matcham: None Declared, K. White: None Declared, J. Haro: None Declared, S. Siddi: None Declared, S. Vairavan Employee of: S.V is an employee of Janssen Research & Development, LLC and hold company stocks/stock options., B. Penninx : None Declared, V. Narayan: None Declared, M. Hotopf Grant / Research support from: M.H. is the principal investigator of the RADAR-CNS programme, a precompetitive public–private partnership funded by the Innovative Medicines Initiative and the European Federation of Pharmaceutical Industries and Associations. The programme received support from Janssen, Biogen, MSD, UCB and Lundbeck., E. Carr: None Declared
Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.
Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity.
Methods
Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions.
Results
Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms.
Conclusions
Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.
Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an exciting opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks.
Objectives
To describe the amount of data collected during a multimodal longitudinal RMT study, in an MDD population.
Methods
RADAR-MDD is a multi-centre, prospective observational cohort study. People with a history of MDD were provided with a wrist-worn wearable, and several apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks and cognitive assessments and followed-up for a maximum of 2 years.
Results
A total of 623 individuals with a history of MDD were enrolled in the study with 80% completion rates for primary outcome assessments across all timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. Data availability across all RMT data types varied depending on the source of data and the participant-burden for each data type. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. 110 participants had > 50% data available across all data types, and thus able to contribute to multiparametric analyses.
Conclusions
RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible.
To determine associations of alcohol use with cognitive aging among middle-aged men.
Method:
1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003–2007 to 2016–2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1–4 drinks in past 14 days), light (5–14 drinks), moderate (15–28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors.
Results:
Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by –0.21 SD (95% CI –0.35, –0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, –0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association.
Conclusions:
Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.
Recursive formulae satisfied by the Fourier coefficients of meromorphic modular forms on groups of genus zero have been investigated by several authors. Bruinier et al. [‘The arithmetic of the values of modular functions and the divisors of modular forms’, Compositio Math. 140(3) (2004), 552–566] found recurrences for SL(2,ℤ); Ahlgren [‘The theta-operator and the divisors of modular forms on genus zero subgroups’, Math. Res. Lett.10(5–6) (2003), 787–798] investigated the groups Γ0(p); Atkinson [‘Divisors of modular forms on Γ0(4)’, J. Number Theory112(1) (2005), 189–204] considered Γ0(4), and S. Y. Choi [‘The values of modular functions and modular forms’, Canad. Math. Bull.49(4) (2006), 526–535] found the corresponding formulae for the groups Γ+0(p). In this paper we generalize these results and find recursive formulae for the Fourier coefficients of any meromorphic modular form f on any genus-zero group Γ commensurable with SL(2,ℤ) , including noncongruence groups and expansions at irregular cusps. The form of the recurrence relations is well suited for the computation of the Fourier coefficients of the functions and forms on the groups which occur in monstrous and generalized moonshine. The required initial data has, in many cases, been computed by Norton (private communication).
We compared reproductive characteristics of the dendrobatid frog Colostethus trinitatis at the Tamana cave in the Central Range hills and at five forest stream sites in the Northern Range hills of Trinidad. There were significant differences between sites in adult female body size, intraovarian clutch size (in absolute terms and relative to body size) and the size of tadpoles carried by male frogs. Clutch sizes ranged from 6 to 13 in the Northern Range samples and from 12 to 26 at Tamana. Adult male body size was similar at all sites. Tadpoles carried by male C. trinitatis at Tamana were significantly smaller (mean length 14.2 mm) than those carried by males at the five Northern range sites (mean length 16.4–16.7 mm). The smallest clutches and largest tadpoles were found at Mount St Benedict, where there was evidence of size-selective predation on tadpoles by fish. Tamana, where clutches were large and tadpoles small, differed from the Northern Range sites in terms of the physical environment (cave vs forest) and the abundance of invertebrates. We discuss possible ultimate and proximate causes of the differences in clutch size and tadpole size, particularly size-selective predation and availability of food.
Two natural human interferon alpha preparations, (nHuIFN-μ [Cantell]) and (Nhuifn-μ [ISI]), were used for the oral treatment of cattle experimentally infected with Theileria parva parva. In the first experiment, 8 Friesian bulls were inoculated with a 1 in 10 dilution of a sporozoite stabilate of T. p. parva (Marikebuni) stock. Four of the cattle were treated daily with 1 international unit/kg body weight (i.u./kg bwt) of nHuIFN-μ (Cantell) from day –2 to day 8 p.i. None of the 4 calves given IFN developed clinical theileriosis, but 3 of the 4 control calves died of theileriosis while the fourth had a mild infection. Three of 4 treated calves and the 1 surviving control calf developed a detectable antibody response to T. p. parva schizont antigen but, on challenged with a 10-fold higher dose of stabilate, the surviving control animal and only 1 of the 4 treated calves proved to be immune. In a second experiment, 4 groups of 4 calves were inoculated with the same stabilate dilution. Three treatment groups were given either 1 i.u. nHuIFN-μ (Cantell), 1 i.u. nHuIFN-μ (ISI), or 10 i.u. nHuIFN-μ (ISI)/kg bwt from day –2 to day 8 p.i. once daily and the fourth group were controls. Clinical theileriosis occurred in 2 controls, 2 calves given 10 i.u. nHuINF-μ (ISI), 1 calf given 1 i.u. nHuIFN-μ (ISI) and no calves given 1 i.u. nHuIFN-μ (Cantell)/kg bwt. Of these, 2, 1, 0 and 0 cattle died in the respective groups. All the surviving cattle proved to be immune on homologous challenge with 10-fold higher dose of stabilate except the 2 cattle which did not develop high antibody responses. A third experiment using an undiluted challenge of T. p. parva (Muguga) sporozoite stabilate (10α) on 8 steers. Four steers were treated with 1 i.u. nHuIFN-α (Cantell)/kg bwt and 4 were controls. All calves developed acute theileriosis and the experiment was terminated. Cells of the C2 lymphoblastoid cell line, infected with T. p. parva (Muguga) schizonts, were cultured in vitro with various concentrations (0-01-100 i.u./ml) of nHuIFN-a (Cantell). The IFN appeared to have no effect on host cell or parasite developmental variables when compared to untreated control cultures.
To develop an objective, nutrient-based, healthy eating indicator shopping basket (HEISB) tool for use in studies of access to healthy food.
Design
Tool development used a literature search to identify previous practice, web information on current definition of healthy foods by the UK Food Standards Agency, and population-based dietary surveys to identify culturally acceptable foods. These findings were then appraised with respect to practical fieldwork considerations.
Setting
The review took account of surveys undertaken in a range of geographical areas.
Results
Previous tools have varied in the foods selected and the rationale for inclusion. Most have considered nutritional composition but no systematic definition has been used and foods have been subjectively classified as ‘less healthy’ or ‘more healthy’. Recent UK work on nutrient profiling enabled individual food items to be objectively assessed for inclusion. Data from national food surveys enabled commonly consumed and culturally acceptable foods to be identified. Practical considerations included item use in meals, convenience, price, and fieldwork constraints. Other issues including health and price discriminators as well as regional preferences were considered. The final HEISB tool comprised 35 items within the following categories – 17 from fruit and vegetables, nine from potatoes, bread and cereal, five from fish/meats, three from dairy, and one from fatty and sugary foods.
Conclusions
The tool provides a rational basis for examining access and availability of healthy foods in cross-sectional and longitudinal retail and consumer studies.
Residual feed intake (RFI) is a measure of feed efficiency calculated as the difference between an animal’s actual intake and its expected intake based on its liveweight and growth rate over a specified period of time (Richardson, Herd et al. 2002). The efficiency with which an animal utilises energy during growth, is dependent on a number of physiological factors including body composition and the relative proportions of lean tissue mass (LTM) and fat tissue mass (FTM), due to differences in the energy cost of depositing and maintaining these tissues. Protein or lean tissue is continually degraded and resynthesised and thus the rate at which this occurs may contribute to the variation in energy required by an animal for maintenance and growth (Archer, Richardson et al. 1999). The objective of this work was to determine the relationship between feed conversion ratio (FCR, kg feed:kg gain) and residual feed intake (RFI) with body composition in rams at six months of age (6mo), and then again in the same rams at thirteen months of age (13mo).
The constructive interference between direct and indirect channels above the absorption threshold of a core level leads to a massive increase in the emission cross section leading to a phenomenon called “resonant photoemission”. Using novel magnetic linear dichroism in angular distribution photoelectron spectroscopy experiment we have tried to understand the nature of the resonant photoemission process in Gd metal. The presence of dichroism in Gd 4f photoemission intensity at a photon energy corresponding to resonant photoemission clearly demonstrates the photoemission-like nature of the resonant photoemission process.
It is shown that if ƒ is a Hauptmodul with rational integer coefficients for a group G < PGL2(ℚ)+, of genus zero, containing a with finite index and z ⟼ z+k precisely when k is an integer, then ƒ is replicable. Examples of such functions are given by the Moonshine functions described by Conway and Norton [CN].