Within-person Changes Research Articles

Longitudinal validity of the Hyperhidrosis Quality of Life Index (HidroQoL©) in a phase IIIb clinical trial population with hyperhidrosis: responsiveness and meaningful change.

The Hyperhidrosis Quality of Life Index (HidroQoL ©) is a well-developed patient-reported outcome measure assessing the quality of life (QoL) impacts in hyperhidrosis, which has proven very good measurement properties, such as structural validity and internal consistency. We aimed to investigate responsiveness over time and estimate values for meaningful within-person change (MWPC) towards symptom improvement for different measurement time points (4 and 12 weeks), extending the existing validity evidence in patients with primary axillary hyperhidrosis. Data (from a phase IIIb clinical trial) was collected at baseline, week 4, week 8, week 12, week 28, week 52, and week 72. For the assessment of responsiveness, HidroQoL change scores were correlated with corresponding change scores of the Hyperhidrosis Disease Severity Scale (HDSS), the Dermatology Life Quality Index (DLQI), and the gravimetric sweat production based on a-priori formulated hypotheses. Furthermore, it was tested whether the different HDSS change score groups differed significantly from each other over time and whether the HidroQoL was sensitive towards these group differences over time. This was extended by the calculation of matched-pair tests and effect sizes to test significance for each change group separately. For the estimation of MWPC thresholds towards symptom improvement, different anchor-based and integrated approaches were used. In total, the sample was composed of 357 patients with primary axillary hyperhidrosis. For the assessment of responsiveness, 5 out of 14 a-priori hypotheses regarding the correlation of the change scores could be confirmed, whereas the rejected hypotheses only marginally differed from the expected values. Furthermore, regarding responsiveness, the HidroQoL showed sensitivity towards symptom improvement at each measurement time point. Effect sizes were large as expected (d ≥ 0.806). MWPC thresholds towards symptom improvement were proposed for two measurement time points: 5 (week 4) and 6 (week 12). Increasing MWPC values over time were observed. This study extends the evidence for the longitudinal validity of the HidroQoL up to 72 weeks and proposed MWPC thresholds for different time intervals (4 and 12 weeks) after baseline, aiding interpretability. Results concur with findings from previous validation studies.

Fluctuations in Prejudice Do Not Track Fluctuations in Ordinary Contact in Three 5-Wave “Shortitudinal” Studies Examining Daily, Weekly, or Monthly Intervals

Intergroup contact is regarded as one of the most effective ways to reduce prejudice. However, recent longitudinal studies using contemporary statistical techniques (e.g., random intercept cross-lagged panel models [RI-CLPMs]) have failed to find evidence of within-person changes in prejudice following contact fluctuations. We propose that past time-lags may have been too long to capture change and conducted three studies with shorter time-lags of single days, weeks, or months. We also considered effects of positive versus negative contact frequency. We consistently found that people who are less prejudiced have more contact (i.e., between-person effects); however, fluctuations in naturally occurring contact were not followed by corresponding within-person changes in prejudice, suggesting shorter-term contact fluctuations are detached from prejudice. With abundant support for contact in the field, we argue that prejudice may be impacted by major contact events, or through gradually acquired cumulative experiences, but effects are not apparent when examining “thin-slices” of time.

Personal Relative Deprivation and Locus of Control.

We investigated the relationship between personal relative deprivation (PRD)-resentment from the belief that one is worse off than people who are similar to oneself-and locus of control. Research has yet to comprehensively investigate whether PRD is associated with a tendency to favor external (vs. internal) explanations for self- and other-relevant outcomes. Eight studies (Ntotal = 6729) employed cross-sectional, experimental, and (micro)longitudinal designs and used established trait and state measures of PRD and loci of control. Participants higher in PRD adopted more external (vs. internal) explanations for others' outcomes while controlling for socio-demographics (e.g., socioeconomic status; Studies 1-4). This relationship was mediated by a lowered sense of personal control (Study 1) and evident in a cross-national sample of participants in Asia (Study 2). PRD is more robustly associated with external than internal explanations for self and other-relevant outcomes (Studies 5-8), and within-person changes in PRD are positively associated with within-person changes in external explanations (month-to-month and day-to-day; Studies 7-8). PRD is positively associated with external locus of control independent of socioeconomic status, within and between people, and across cultures. This research highlights the implications of PRD for people's construal of the causal forces that govern their lives.

A longitudinal study of adolescent pathways differentiating suicide ideation and attempt in early adulthood.

Suicide ideation and attempt are leading risk factors for mortality in young adults. However, the adolescent risk factors distinguishing suicide ideation from attempt in young adults remain unclear. The present study aimed to examine the extent to which within-person stability and change in depressive symptoms, school difficulties, and peer victimization from ages 12 to 17 were differentially associated with later suicide ideation and attempt from ages 20 to 23. The study included 1647 participants from the Quebec Longitudinal Study of Child Development (QLSCD; 52% female). Participants reported on their depressive symptoms, school difficulties, and peer victimization at ages 12, 13, 15, and 17, and on suicide ideation and attempt at ages 20 and 23. Data were collected in the Province of Quebec, Canada, between 2010 and 2021. Results indicated that 11% (N = 121) and 8% (N = 86) reported suicide ideation and attempt, respectively, between ages 20 and 23. A random-intercept cross-lagged panel model showed that within-person increases in depressive symptoms during adolescence were related to both suicide ideation and attempt, whereas within-person increases in school difficulties and peer victimization were for the most part related to suicide attempt only. Within-person stability in depressive symptoms from ages 12 to 17 years were also related to suicide attempt, and not ideation. However, this association was only marginally significant. Findings suggest that experiencing unusual rises in school difficulties and peer victimization during adolescence, as well as depressive symptoms persisting over time, may distinguish young adults who think about suicide from those who attempt suicide.

Men and women transitioning to singlehood in young adulthood and midlife.

Research has long shown that men suffer more from romantic breakups than women. We predicted that men would on average be less inclined to initiate separation, decline with the separation more in well-being and increase more in loneliness, are less satisfied with singlehood, and desire a new partner more than women. We theorized that these gender differences in separation adaptation could be linked to men's higher reliance on their partners for emotional support. Because socioemotional selectivity theory suggests that with age people shift toward more fulfilling social connections, we also expected men's dependency on their partners for emotional support to be smaller in midlife than in young adulthood. To examine our hypotheses, we analyzed multiyear within-person longitudinal change data from 1,530 mostly unmarried participants from the annual German pairfam study who had experienced a relationship dissolution. We applied propensity score matching to compare separation-related changes in well-being and loneliness to case-matched controls who remained in a romantic relationship. Results showed that men relative to women were less likely to initiate separation, less satisfied with singlehood, and wished for a partner more. In contrast to our expectations, the gender differences observed did not differ by age, and no gender differences were found in separation-related changes in well-being and loneliness. Dissolution-related effects on well-being were only evident for marital relationships, while dissolution-related effects on loneliness were equally strong for marital and nonmarital dissolutions. Our study suggests that previous findings on gender-specific divorce-induced changes in well-being may not generalize to nonmarital dissolutions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psychosocial determinants of handwashing and physical distancing behaviour during the COVID-19 pandemic in the Netherlands: A longitudinal analysis.

Physical distancing and handwashing can be important infection prevention measures during an infectious disease outbreak such as the COVID-19 pandemic. To stimulate these behaviours, knowledge of psychosocial determinants as well as contextual factors is vital. We present longitudinal, within-person analyses of the impact of contextual and psychosocial factors on handwashing and distancing behaviour. We used individual-level data (186,490 participants completing 971,899 surveys) from the Corona Behavioural Unit COVID-19 Cohort, a dynamic cohort study conducted during 26 months of the COVID-19 pandemic in the Netherlands. Fixed-effects models were employed to estimate within-person associations between psychosocial factors and behaviour, combined with main and moderating effects of contextual factors. Pandemic severity was associated with more handwashing and distancing behaviour, while the duration of the pandemic had little effect. Within-person changes in response efficacy were most relevant for changes in both handwashing and distancing behaviour, while self-efficacy, descriptive norms and perceived severity of infecting others affected behaviour indirectly. These effects were stable over time. Associations were larger in cross-sectional models, indicating that such models tend to overestimate effects. Our study highlights the importance of longitudinal data and within-person models to detect possible causal associations. The results suggest that during an outbreak, government and public health professionals should clearly communicate the severity of the pandemic (e.g., hospitalization rates) and the effectiveness of recommended prevention measures in reducing that risk; and seek to improve people's capabilities and opportunities to adhere to guidelines, for example, by modifying the environment.

A longitudinal study of within-person trajectories in quality of life in patients receiving early palliative care.

To reveal the within-person trajectories in quality of life (QOL) in patients receiving early palliative care. Previous studies have mostly focused aggregated trajectories, based on all research participants combined, whereas this study focused on within-person trajectories in QOL and on whether the variability in QOL trajectories across patients is substantial enough to raise doubts about aggregated trajectories. Twenty-five older persons in early palliative care completed the McGill Quality of Life Questionnaire multiple times. Reliable change analyses provided estimates of the occurrence of statistically significant within-person change. There was reliable, within-person variation in QOL scores across time, more so for physical than for psychological aspects of well-being. Changes in QOL scores occurred for most patients but the trajectories were not linear and there was no common trend in the nonlinear patterns. Reliable change across time can be identified in persons receiving early palliative care. However, the trajectories are notably variable and patient-specific. The high degrees of within-person variability across time suggests the importance of repeated QOL assessments and of dynamic tailoring of clinical treatments.

Study protocol for a pragmatic randomised multiple baseline trial evaluating Knowledge Insight Tools (KIT), a cognitive behavioural therapy-informed school-based counselling intervention for children and young people in UK secondary schools with low mood and anxiety.

There is a pressing need to offer more accessible, evidence-based psychological interventions to secondary school students who are increasingly reporting difficulties with anxiety and low mood. The aim of this pragmatic randomised multiple baseline trial is to evaluate the efficacy of a school-based counselling intervention called Knowledge Insight Tools (KIT) for reducing anxiety and low mood in UK secondary school students. KIT is a flexible intervention delivered individually and informed by cognitive behavioural therapy (CBT). We will use a randomised multiple baseline design whereby young people will be randomly allocated to a baseline wait period of 3, 4, 5, 6, 7, or 8 weekly measurements, followed by receiving up to 10 weekly sessions of KIT delivered by trained, school-based practitioners. We aim to recruit 60 young people aged 11-18 who are primarily experiencing problems with low mood and/or anxiety from secondary schools across England and Scotland. We will assess child-reported anxiety, mood, and general psychological distress/coping with the Young Person's Clinical Outcomes in Routine Evaluation (YP-CORE), recorded at each session during the baseline and intervention phases. We will also assess child-reported anxiety and low mood with the Revised Children's Anxiety and Depression Scale (RCADS) at the beginning and end of treatment; practitioner-reported treatment fidelity with the KIT Fidelity Checklist; and practitioner-reported feasibility with an end-of-treatment Implementation Survey. We will analyse within-person and between-person change in YP-CORE scores across the baseline and intervention phases using visual analysis and piecewise multilevel growth curve models. We will also analyse pre-post changes in YP-CORE scores using randomisation tests, and reliable and clinically significant change using the RCADS scores. The KIT trial is a pragmatic, randomised multiple baseline trial aimed at evaluating a school-based, individual CBTcounselling intervention for reducing anxiety and low mood in UK secondary school students. Results will directly inform the provision of KIT in school-based counselling services, as well as the growing evidence-base for school-based CBT interventions. ClinicalTrials.gov NCT06188962. Retrospectively registered on 02/01/24.

Diet quality from early pregnancy through 1-y postpartum: a prospective cohort study

BackgroundAlthough diet quality during pregnancy and postpartum is important for multiple parent and child outcomes, within-person changes in diet quality throughout these periods have not been extensively examined. ObjectivesThis study investigated diet quality from early pregnancy through 1 y postpartum and examined differences by sociodemographic characteristics in participants receiving obstetric care in Chapel Hill, North Carolina, United States. MethodsParticipants completed 24-h dietary recalls at 6 study visits (each pregnancy trimester and 6 wk, 6 mo, and 1 y postpartum) (n = 383). Between-visit mean Healthy Eating Index-2015 (HEI) scores (min = 0, max = 100) were compared using the population ratio (PR) method. The NCI usual intakes method estimated the distribution of HEI scores in pregnancy and postpartum; unpaired t-tests compared usual mean HEI scores by covariates; paired t-tests compared differences between mean pregnancy and postpartum. ResultsThe total HEI mean ± standard error scores (NCI method) were 61.4 ± 0.8 in pregnancy and 61.7 ± 0.9 in postpartum. Mean HEI scores differed by sociodemographic characteristics, particularly education, marital status, and federal assistance participation. The highest scores were observed in participants with at least a bachelor’s degree (64.1 ± 0.9 in pregnancy, 64.5 ± 1.0 in postpartum, n = 257) and those with other non-Hispanic White race/ethnicity (64.7 ± 1.8 in pregnancy, 66.4 ± 2.2 in postpartum). There were no between-visit differences in mean total HEI scores (PR). Although differences were observed in some mean HEI component scores between pregnancy and postpartum visits, they were small (mostly <1 point) in magnitude and in inconsistent directions. ConclusionsStable total HEI mean scores suggest that adherence to dietary guidelines was consistent throughout pregnancy and postpartum in this sample. Although some sociodemographic characteristics may identify individuals at greater risk of diet-related pregnancy complications, low diet quality was pervasive throughout all subgroups and reflects an urgent need for widespread improvement.

Lagged effects of childhood depressive symptoms on adult epigenetic aging.

Cross-sectional studies have identified health risks associated with epigenetic aging. However, it is unclear whether these risks make epigenetic clocks 'tick faster' (i.e. accelerate biological aging). The current study examines concurrent and lagged within-person changes of a variety of health risks associated with epigenetic aging. Individuals from the Great Smoky Mountains Study were followed from age 9 to 35 years. DNA methylation profiles were assessed from blood, at multiple timepoints (i.e. waves) for each individual. Health risks were psychiatric, lifestyle, and adversity factors. Concurrent (N = 539 individuals; 1029 assessments) and lagged (N = 380 individuals; 760 assessments) analyses were used to determine the link between health risks and epigenetic aging. Concurrent models showed that BMI (r = 0.15, PFDR < 0.01) was significantly correlated to epigenetic aging at the subject-level but not wave-level. Lagged models demonstrated that depressive symptoms (b = 1.67 months per symptom, PFDR = 0.02) in adolescence accelerated epigenetic aging in adulthood, also when models were fully adjusted for BMI, smoking, and cannabis and alcohol use. Within-persons, changes in health risks were unaccompanied by concurrent changes in epigenetic aging, suggesting that it is unlikely for risks to immediately 'accelerate' epigenetic aging. However, time lagged analyses indicated that depressive symptoms in childhood/adolescence predicted epigenetic aging in adulthood. Together, findings suggest that age-related biological embedding of depressive symptoms is not instant but provides prognostic opportunities. Repeated measurements and longer follow-up times are needed to examine stable and dynamic contributions of childhood experiences to epigenetic aging across the lifespan.

Biopsychosocial factors intersecting with weekly sleep difficulties in the menopause transition

ObjectivesSleep difficulties are common in the menopause transition and increase risk for a variety of physical and psychological problems. The current study investigated potential interactions between psychosocial variables and within-person changes in ovarian hormones in predicting perimenopausal sleep problems as well as the potential interactions between poor sleep and psychosocial factors in predicting worsened mood, affect, and attention. Study designThe sample included 101 perimenopausal individuals. Participants completed 12 weekly assessments of self-reported sleep outcomes, depressive mood and affect, and attention function, and of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) levels (urinary metabolites of estradiol and progesterone, respectively); they also had 24-h tracking of vasomotor symptoms. Other psychosocial variables such as trauma history and stressful life events were assessed at baseline. ResultsA history of depression, baseline depressive symptoms, trait anxiety, and more severe and bothersome vasomotor symptoms predicted worsened sleep outcomes. Recent stressful life events, trauma history, and person-centred E1G and PdG changes did not predict sleep outcomes. However, there was an interaction whereby person-centred E1G decreases predicted lower sleep efficiency in those with higher baseline depressive symptoms. Higher baseline depression and trauma history also amplified the effect of vasomotor symptoms on sleep outcomes. In evaluating the effect of poor sleep on psychological and cognitive outcomes, stressful life events emerged as a moderating factor. Finally, trauma history and poor sleep interacted to predict worsened attention function. ConclusionsThe current study suggests that certain individuals may be at greater risk of perimenopausal sleep problems and the resulting negative effects on mood and cognition.

“I’m both smoking and vaping”: a longitudinal qualitative study of US young adults who tried to quit smoking cigarettes by using electronic cigarettes

ObjectiveTo describe how young adults use electronic cigarettes (electronic nicotine delivery systems (ENDS)) for smoking cessation and reasons why they may or may not successfully quit smoking.MethodsLongitudinal qualitative data were...

Prolonged perceived stress predicts fingernail cortisol increase: A longitudinal study

Cortisol levels in fingernail samples are known to represent cumulative hormone levels. However, findings on the association between fingernail cortisol and perceived stress have been inconsistent. Since the effect of confounding factors cannot be excluded in cross-sectional studies, this study longitudinally examined the effects of perceived stress and negative life events on changes in fingernail cortisol levels over a period of six months. In total, 113 university students rated their perceived stress and negative life events twice, fingernail samples were collected every 15 days during a six-month period. Furthermore, fingernail cortisol levels were quantified according to each stress and negative life event assessment. We conducted longitudinal multilevel analyses to estimate the effects of perceived stress and negative life events in changes within an individual (within-person change) as well as individual differences of them over the study period (between-person level) on changes in fingernail cortisol levels. Within-person increase in perceived stress and negative life events did not significantly predict within-person increase in fingernail cortisol levels. In the between-person level, higher average levels of negative life events did not significantly predict the rate of increase in fingernail cortisol levels than those with lower levels. However, individuals with higher average levels of perceived stress showed a steeper slope of time in fingernail cortisol levels. These findings suggest that prolonged high levels of perceived stress may be associated with fingernail cortisol levels.

Neighbourhood environments and cognitive health in the longitudinal Personality and Total Health (PATH) through life study: A 12-year follow-up of older Australians

BackgroundUrban neighbourhood environments may impact older adults’ cognitive health. However, longitudinal studies examining key environmental correlates of cognitive health are lacking. We estimated cross-sectional and longitudinal associations of neighbourhood built and natural environments and ambient air pollution with multiple cognitive health outcomes in Australian urban dwellers aged 60+ years. MethodsThe study included 1160 participants of the PATH Through Life study (60+ cohort) who were followed up for 12 years (four assessments; 2001/02 to 2013/15) and with data on socio-demographics, health, cognitive functions and diagnoses, and full residential address. Neighbourhood environmental features encompassed population and street-intersection densities, non-commercial land use mix, transit points, presence of blue space, percentages of commercial land, parkland and tree cover, and annual average PM2.5 and NO2 concentrations. All exposures except for tree cover were assessed at two time points. Generalised additive mixed models estimated associations of person-level average, and within-person changes in, exposures with cognitive functions. Multi-state hidden Markov models estimated the associations of neighbourhood attributes with transitions to/from mild cognitive impairment (MCI). ResultsDense, destination-rich neighbourhoods were associated with a lower likelihood of transition to MCI and reversal to no MCI. Positive cross-sectional and longitudinal associations of non-commercial land use mix, street intersection density and percentage of commercial land were observed especially with global cognition and processing speed. While access to parkland and blue spaces were associated with a lower risk of transition to MCI, the findings related to cognitive functions were mixed and supportive of an effect of parkland on verbal memory only. Higher levels of PM2.5 and NO2 were consistently associated with steeper declines and/or decreases in cognitive functions and worse cognitive states across time. ConclusionTo support cognitive health in ageing populations, neighbourhoods need to provide an optimal mix of environmental complexity, destinations and access to the natural environment and, at the same time, minimise ambient air pollution.

A Note on the Occurrence of the Illusory Between-Person Component in the Random Intercept Cross-Lagged Panel Model

The random intercept cross-lagged panel model (RICLPM) decomposes longitudinal associations between two processes X and Y into stable between-person associations and temporal within-person changes. In a recent study, Bailey et al. demonstrated through a simulation study that the between-person variance components in the RICLPM can occur only due to the presence of time-varying covariate processes that are omitted from the analysis model. Therefore, the between-person component was termed illusory. In this article, necessary and sufficient conditions for the occurrence of such illusory between-person components in an RICLPM are analytically derived and systematically investigated in a simulation study.

Acceptability, engagement, and preliminary efficacy of a college human physiology course with integrated mindfulness practice to support student wellbeing.

To evaluate the acceptability of and engagement with an undergraduate human physiology course embedded with mindfulness practice. To assess its preliminary efficacy on student mindfulness and wellbeing. Students (N = 36, 17% freshman, 33% sophomore, 22% junior, and 28% senior) answered online surveys at course completion. Primary outcomes were course ratings, assignment and assessment completion rates, minutes, types of mindfulness practice, changes in trait mindfulness (Mindful Attention Awareness Scale, MAAS), and self-reported wellbeing outcomes. We ran Chi-square goodness of fit tests and paired Wilcoxon signed-rank tests to decide if the outcomes differed significantly post-class. We tested the dose-response relation between mindfulness practice time and trait mindfulness and whether the out-of-class practice time was consistent across the weeks with generalized linear mixed-effect models. All participants reported finding the course enjoyable and that they would recommend it to their friends. They practiced for an average of 66 (SD = 27) min per week in the class and 112 (SD = 59) min on their own. The most common out-of-class practices were mindful movements, sitting meditation, and breathing. Per self-reports, the course increased student understanding of specific mindfulness practices and appreciation for their body. It improved wellbeing and trait mindfulness (MAAS mean within-person change = 1.2, SD = 0.8, p < 0.00001). We found no does-response relation between practice time and trait mindfulness. This pilot study supports that incorporating mindfulness practice into college-level courses may promote student wellbeing and such approaches warrant further investigation.

Short-Term Coupling Associations Between State Loneliness and Cognitive Performance in Daily Life Among Older Adults.

Despite extensive efforts to study individual differences in loneliness and neurocognitive health, little is known about how within-person changes in state loneliness relate to cognitive performance. This study addressed this gap by examining the association between within-person variation in state loneliness and cognitive performance assessed objectively in daily life. Participants were 313 community-dwelling older adults (70-90 years) who reported momentary feelings of loneliness and completed smartphone-based cognitive tests 5 times daily for 14 consecutive days. Mobile cognitive tests assess visual associative memory, processing speed, and spatial memory. At the day level, average state loneliness levels were negatively related to cognitive performance on the same day and subsequent day. Consistent with the day-level analysis, momentary assessments of increased loneliness were consistently linked to worse cognitive performance on concurrent assessments. However, moments characterized by lower cognitive performance predicted higher levels of loneliness 3-4hr later (next occasion), but not vice versa. The findings suggest a prospective association between loneliness and cognitive performance, with higher daily loneliness negatively associated with cognitive performance on the same day and predicting worse performance the following day. Notably, within a single day, lower cognitive performance at a given moment predicted elevated loneliness later in the day. This highlights a complex, reciprocal relationship-loneliness predicting and being predicted by cognitive performance depending on timescale.

Cross-sectional and longitudinal changes in mind-wandering in older adulthood.

Age-related declines in the frequency of mind-wandering are well established. Theories of mind-wandering have attempted to explain why this decline occurs, but no one theory firmly predicts such changes. One problem with these theoretical views, and the studies that have grown out of them, is their reliance on cross-sectional methods, which do not account for within-person changes over time in mind-wandering, and it is well-documented that cross-sectional and longitudinal changes in some cognitive domains do not align. We present a novel analysis of longitudinal change in subjective and objective indicators of mind-wandering during a sustained attention task. Cognitively normal adults (N = 277, age range 42-94) completed a sustained attention task with thought probes to measure mind-wandering repeatedly over several years. Linear mixed effect models revealed baseline differences in subjective mind-wandering reports among middle-aged and older adults. However, longitudinally, middle-aged participants showed a significant increase in subjective mind-wandering, whereas older participants showed no change. Changes in mind-wandering could not be explained by attentional control ability or contemporaneous estimates of interest and perceived difficulty, but they were explained by baseline levels of conscientiousness. Objective measures of mind-wandering did not show these same patterns and were largely only associated with participants perceived difficulty. Our results build on previous cross-sectional research and suggest that incorporating longitudinal analyses into theories of ageing and mind-wandering and mind-wandering more broadly is important for refining these theories. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Within-person biological mechanisms of mood variability in childhood and adolescence.

Mood variability, the day-to-day fluctuation in mood, differs between individuals and develops during adolescence. Because adolescents show higher mood variability and average mood than children and adults, puberty might be a potential biological mechanism underlying this increase. The goal of this preregistered developmental study was to examine the neural and hormonal underpinnings of adolescent-specific within-person changes in mood variability, with a specific focus on testosterone, cortisol, pubertal status, and resting-state functional brain connectivity. Data from two longitudinal cohorts were used: the L-CID twin study (aged 7-13, N at the first timepoint = 258) and the accelerated Leiden Self-Concept study (SC; aged 11-21, N at the first timepoint = 138). In both studies resting-state functional magnetic resonance imaging (rs-fMRI) data was collected, as well as daily mood. Additionally, in the SC study self-reported puberty testosterone and cortisol were collected. Random intercept cross-lagged panel models (RI-CLPM) were used to study the within-person relations between these biological measures and mood variability and average mood. Mood variability and average mood peaked in adolescence and testosterone levels and self-reported puberty also showed an increase. Connectivity between prefrontal cortex (dlPFC and vmPFC) and subcortical regions (caudate, amygdala) decreased across development. Moreover, higher testosterone predicted average negative mood at the next time point, but not vice versa. Further, stronger vmPFC-amygdala functional connectivity predicted decreases in mood variability. Here, we show that brain connectivity during development is an important within-person biological mechanism of the development of mood in adolescents. PRACTITIONER POINTS: Mood variability peaks in adolescence. Within-person changes in testosterone predict within-person changes in mood. Within-person changes in vmPFC-amygdala connectivity predict within-person changes in mood variability.

Estimating risk of consequences following hypoglycaemia exposure using the Hypo-RESOLVE cohort: a secondary analysis of pooled data from insulin clinical trials

Aims/hypothesisWhether hypoglycaemia increases the risk of other adverse outcomes in diabetes remains controversial, especially for hypoglycaemia episodes not requiring assistance from another person. An objective of the Hypoglycaemia REdefining SOLutions for better liVEs (Hypo-RESOLVE) project was to create and use a dataset of pooled clinical trials in people with type 1 or type 2 diabetes to examine the association of exposure to all hypoglycaemia episodes across the range of severity with incident event outcomes: death, CVD, neuropathy, kidney disease, retinal disorders and depression. We also examined the change in continuous outcomes that occurred following a hypoglycaemia episode: change in eGFR, HbA1c, blood glucose, blood glucose variability and weight.MethodsData from 84 trials with 39,373 participants were pooled. For event outcomes, time-updated Cox regression models adjusted for age, sex, diabetes duration and HbA1c were fitted to assess association between: (1) outcome and cumulative exposure to hypoglycaemia episodes; and (2) outcomes where an acute effect might be expected (i.e. death, acute CVD, retinal disorders) and any hypoglycaemia exposure within the last 10 days. Exposures to any hypoglycaemia episode and to episodes of given severity (levels 1, 2 and 3) were examined. Further adjustment was then made for a wider set of potential confounders. The within-person change in continuous outcomes was also summarised (median of 40.4 weeks for type 1 diabetes and 26 weeks for type 2 diabetes). Analyses were conducted separately by type of diabetes.ResultsThe maximally adjusted association analysis for type 1 diabetes found that cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of neuropathy, kidney disease, retinal disorders and depression, with risk ratios ranging from 1.55 (p=0.002) to 2.81 (p=0.002). Associations of a similar direction were found when level 1 episodes were examined separately but were significant for depression only. For type 2 diabetes cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of death, acute CVD, kidney disease, retinal disorders and depression, with risk ratios ranging from 2.35 (p<0.0001) to 3.00 (p<0.0001). These associations remained significant when level 1 episodes were examined separately. There was evidence of an association between hypoglycaemia episodes of any kind in the previous 10 days and death, acute CVD and retinal disorders in both type 1 and type 2 diabetes, with rate ratios ranging from 1.32 (p=0.017) to 2.68 (p<0.0001). These associations varied in magnitude and significance when examined separately by hypoglycaemia level. Within the range of hypoglycaemia defined by levels 1, 2 and 3, we could not find any evidence of a threshold at which risk of these consequences suddenly became pronounced.Conclusions/interpretationThese data are consistent with hypoglycaemia being associated with an increased risk of adverse events across several body systems in diabetes. These associations are not confined to severe hypoglycaemia requiring assistance.Graphical