Naomi P. Friedman

Chronic pain affects brain gray matter structure, but the magnitude, pattern, and reversibility of brain changes upon pain recovery remain unclear because of inconsistent findings from small-scale studies. We analyzed data from 35,052 UK Biobank participants who completed chronic pain assessments at 2 time points, approximately 9 years apart, evaluating pain lasting 3 months or more, across 8 body sites. Brain magnetic resonance imaging data were available from the second time point. Participants were grouped into 4 categories: Pain-free controls, New chronic pain, Persistent chronic pain, and Resolved chronic pain. We examined relationships between these categories and 313 brain-wide measures across cortical surface area, cortical thickness, and subcortical volume. New chronic pain was associated with surface area reductions in sensorimotor, temporo-parietal, and medial and lateral prefrontal cortices. Persistent chronic pain showed larger and more widespread area reductions and mixed changes in cortical thickness and subcortical volumes, including cerebellar atrophy and hypertrophy in the thalamus and basal ganglia. Resolved pain demonstrated reversibility of most brain changes, except sustained surface area reductions in the primary somatosensory cortex. No areas showed effects consistent with a predisposition to pain. Brain structural changes in chronic pain reflect adaptive neuroplasticity rather than irreversible damage or preexisting vulnerability. Most changes appear reversible with pain resolution, underscoring the importance of effective pain treatment to alleviate symptoms and support recovery of brain structure and function.

Background and Objectives: Cognitive dispersion, reflecting intraindividual variability across tasks, may signal dementia risk in older adults, but its origins and relevance before midlife are unclear. We examined dispersion as a potential marker of cognitive reserve in established adulthood and distinguished it from general ability using heritability analyses. Research Design and Methods: 1,245 primarily non-Hispanic White twins and siblings were assessed at 33.3 years (SD = 5.0; 53% female) using 2 cognitive batteries. Bayesian mixed effects location scale models estimated mean performance and dispersion across cognitive tasks, with tasks standardized against current sample-based norms (age 33) and adolescent norms (age 16). The mean of task scores standardized to current norms reflects current ability, while the mean of the same scores standardized to adolescent norms reflects growth in ability. The respective dispersion estimates represent task-specific deviations from general ability and task-specific gains. Results: Across 4 models fitted by battery and standardization, greater cognitive dispersion was associated with higher general ability (r = 0.23–0.56) and developmental gains (r = 0.62–0.93). Verbal tasks showed lower dispersion relative to performance tasks (β = 0.83–0.87). Dispersion was strongly heritable overall (43%–84%), and moderately heritable independent of general ability (36%–37%) and growth (2%–16%). Dispersion did not predict education or occupational outcomes beyond general ability and growth. Discussion and Implications: Before midlife, cognitive dispersion is distinct from general ability and moderately heritable. Dispersion is associated with higher cognitive ability and growth, but not directly with educational or occupational attainment, suggesting dispersion may relate to cognitive reserve through other pathways.

Executive-function (EF) deficits are a putative risk factor for adolescent depression, but neural correlates of this association remain unclear. Imbalances between externally and internally oriented attention underlying depression risk may be reflected in altered temporal dynamics of large-scale functional brain networks. In this longitudinal study, we evaluated neural correlates of EF-related depression risk in an adolescent sample ( N = 154, ages 13–19). We applied coactivation pattern analysis to identify transient network states occurring during a working memory (WM) task and dynamic structural equation modeling to model depressive-symptom trajectories over 2 years. Results failed to support general EF as predictor of symptoms, but exploratory analyses revealed that WM deficits during low-load conditions predicted greater depression variability. WM-related risk for depression was partially mediated by longer persistence of a transient network involving coactivation of frontoparietal regions. Findings suggest that WM deficits and related temporal dynamics of frontoparietal regions may contribute to depression risk.

Previous studies have suggested that alterations in white matter (WM) microstructure are implicated in suicidal thoughts and behaviours (STBs). However, findings of diffusion tensor imaging (DTI) studies have been inconsistent. In this large-scale mega-analysis conducted by the ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium, we examined WM alterations associated with STBs. Data processing was standardised across sites, and resulting WM microstructure measures (fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity and radial diffusivity) for 24 WM tracts and one global measure were pooled across 40 cohorts. We compared these measures among individuals with a psychiatric diagnosis and lifetime history of suicide attempt ( n = 652; mean age = 35.4 ± 14.7; female = 71.8%), individuals with a psychiatric diagnosis but no STB (i.e., clinical controls; n = 1871; mean age = 34 ± 14.8; female = 59.8%), and individuals with no psychiatric diagnosis and no STB (i.e., healthy controls; n = 642; mean age = 29.6 ± 13.1; female = 62.9%). We also compared these measures among individuals with recent suicidal ideation ( n = 714; mean age = 36.3 ± 15.3; female = 66.1%), clinical controls ( n = 1184; mean age = 36.8 ± 15.6; female = 63.1%), and healthy controls ( n = 1240; mean age = 31.6 ± 15.5; female = 61.0%). We found subtle but statistically significant effects, such as lower FA associated with a history of suicide attempt, over and above the effect of psychiatric diagnoses. These effects were strongest in the corona radiata, thalamic radiation, fornix/stria terminalis, corpus callosum and superior longitudinal fasciculus. Recent suicidal ideation was associated with higher AD in the cingulum. Effect sizes were small (partial eta-squared < 0.015). This large-scale coordinated mega-analysis revealed subtle regional and global alterations in WM microstructure in individuals with a history of suicide attempt and recent suicidal ideation. Longitudinal studies are needed to confirm whether these alterations are a risk factor for suicidal behaviour or ideation.

Measures of general cognitive ability (GCA) are highly stable from adolescence onward, particularly at the level of genetic influences. In contrast, measurement of GCA in early life (before 3 y old) is less reliable and less is known about the stability of GCA across this period, including its relation to adult GCA. Using data from the Colorado Longitudinal Twin study (N = 1,098), we examined the stability of GCA measures across 5 time-points (years 1 to 2, 3, 7, 16, and 29), including how an array of cognitive measures given at 7 and 9 mo relate to later GCA. We then examined the genetic and environmental stability of GCA across the first 30 y of life using complementary methods: twin analyses and polygenic scores (PGSs). Two infant cognition measures, object novelty and tester-rated task orientation, predicted GCA in adulthood ( r = 0.16 and 0.18, respectively). Correlational analyses were consistent with a pattern of increasing stability across development for GCA measures between year 1 to 2 and adulthood ( r = 0.39 to 0.85). Subsequent twin analyses revealed that 22% of variance in adulthood GCA was captured by genetic influences on GCA from year 3 or earlier, with an additional 10% explained by shared environmental influences on GCA at year 1 to 2. PGSs for adulthood GCA and educational attainment predicted GCA from 1 to 2 y onward ( β s = 0.09 to 0.44) but not infant cognition. Findings suggest that genetic and environmental influences on GCA demonstrate considerable stability as early as age 3 y, but that measures of infant cognition are less predictive of later cognitive ability.

Abnormalities in reward sensitivity and cognitive control are observed in multiple psychiatric disorders. However, differences in measurement strategies for evaluating reward sensitivity and cognitive control across studies have yielded mixed findings. Despite assumptions of convergence, the correlation between survey-based and task-based assessments of these constructs remains small. In this preregistered study of data from the Adolescent Brain and Cognitive Development (ABCD) sample (N=11,875; ages 9-12), we found evidence for multiple cognitive control and reward sensitivity factors with modest correlations. Factors segregated by construct but also by method (task-based vs. survey), and survey rater (self vs. caregiver). Cognitive control and reward sensitivity independently predicted both internalizing and externalizing psychopathology factors two years later (Beta= 0.01 to |.605|) with multiple factors appearing transdiagnostic. Our findings highlight the complementary predictive power of these multi-method and multi-rater factors, each contributing unique information about risk for psychopathology in adolescence.

Background: The onset of the COVID-19 pandemic in early 2020 introduced unprecedented disruptions impacting the emotional well-being and daily routines of US youths. However, the patterns and persistence of these impacts over the pandemic’s multiyear course remain less well understood. Objective: This study examined longitudinal changes in affect and daily mobility patterns observed in adolescence and young adulthood from June 2016 to April 2022. The study aimed to quantify changes in youths’ mood and daily routines following the pandemic’s onset and in response to local COVID-19 case rates as well as the persistence of these effects over the pandemic’s multiyear course. Methods: Colorado-based adolescent and young adult twins (N=887; n=479, 54% female; meanage 19.2, SDage 1.5 years on January 01, 2020) participating in the CoTwins study between June 2016 and April 2022 were followed via a smartphone app, which recorded persistent GPS location data and, beginning in February 2019, administered an abbreviated Positive and Negative Affect Schedule every 2 weeks. Nonlinear trajectories in affect and daily mobility over time and in response to local COVID-19 counts were modeled via generalized additive mixed models, while the magnitude and persistence of pandemic-related changes were quantified via linear mixed effects regressions. Results: Between January and April 2020, participants experienced a 28.6% decline in daily locations visited (from 3.5 to 2.5; SD 0.9) and a 60% reduction in daily travel distance (from 20.0 to 8.0 km; SD 9.4). Mean positive affect similarly declined by 0.3 SD (from 3.0 to 2.79; SD 0.6), while, correspondingly, mean negative affect increased by 0.3 SD (from 1.85 to 2.10; SD 0.6). Though mobility levels partially recovered beginning in the summer of 2020, daily locations visited remained slightly below 2019 levels through the study’s conclusion in April 2022 (standardized β=–0.10; P<.001). Average positive affect similarly remained slightly below (standardized β=–0.20; P<.001) and negative affect slightly above (standardized β=0.14; P=.04) 2019 levels through April 2022. Weekly county-level COVID-19 transmission rates were negatively associated with mobility and positive affect and positively with negative affect, though these effects were greatly weakened later in the pandemic (eg, early 2022) or when transmission rates were high (eg, >200 new cases per 100,000 people per week). Conclusions: Findings demonstrate large initial declines in daily mobility, a moderate decline in positive affect, and a moderate increase in negative affect following the pandemic’s onset in 2020. Though most effects attenuated over time, affect and mobility levels had not recovered to prepandemic levels by April 2022. Findings support theories of hedonic adaptation and resiliency while also identifying lingering emotional and behavioral consequences. The study highlights both youth’s resiliency in adapting to major stressors while also underscoring the need for continued support for youth mental health and psychosocial functioning in the pandemic’s aftermath.

Mounting evidence supports a prominent neurobiological and psychological component to chronic pain. However, the genetic association between chronic pain, psychiatric conditions, and neuroticism remains unclear. To assess this, we estimated genetic correlations between latent factors for General and Musculoskeletal Pain and Externalizing, Psychotic Thought, Compulsive Thought, and Internalizing psychopathology using genomic structural equation models of published genome-wide association studies. We further estimated the proportion of each pain-psychopathology correlation explained by neuroticism. We observed substantial genetic correlations for the General Pain factor with Internalizing and Externalizing psychiatric factors ( r = .7 for both); genetic correlations with Psychotic and Compulsive Thought disorders were negligible ( r < .2). Neuroticism explained substantial (19%–53%) shared genetic variance for General Pain with Externalizing and Internalizing factors. Overlapping genetic risks for chronic pain, psychiatric conditions, and neuroticism suggest shared biological mechanisms, underscoring the importance of chronic-pain assessment and treatment programs that address these shared mechanisms.