Explore the vast range of titles available.

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness. This review discusses the major challenges facing neuroimaging research of bipolar disorder and highlights the major accomplishments, ongoing challenges and future goals of the ENIGMA Bipolar Disorder Working Group.

Abstract Background Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Design Structural magnetic resonance imaging (MRI) from people with first-episode psychosis and controls (n = 79 and 218) were obtained at enrollment, after 12 months (n = 67 and 197), and 10 years (n = 23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n = 42 983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive and Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects models assessed effects of diagnosis, time, and their interactions on cortical deviations plus associations with symptoms. Results LMEs revealed conditional main effects of diagnosis and time × diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. Conclusions This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.

Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age. Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer. CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions. Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Cortical thickness reductions associated with chronic methamphetamine use exhibit a non-uniform spatial distribution across brain regions. A potential neurobiological mechanism underlying for this heterogeneous pattern may involve the structural and functional organization of cortical connectivity networks, which could mediate the propagation of neuroanatomical alterations. Here, we aimed to explore how brain network architecture constrains cortical thickness alterations and their clinical relevance. The 3D-T1 images were acquired from 139 patients with methamphetamine use disorder (MUD) and 119 sex- and age-matched healthy controls. We first characterized distributed cortical thinning patterns in patients with MUD, then evaluated the relationships between regional atrophy and (1) multimodal nodal centrality measures (structural, morphological, and functional) and (2) atrophy profiles of structural connected neighbors. Individual network-weighted cortical abnormality maps were used to identify distinct MUD biotypes and related to clinical features through k-means clustering and partial least squares regression. Cortical thinning patterns demonstrated significant associations with nodal centrality across all modalities, as well as cortical thinning of connected neighbors revealing a network-dependent atrophy architecture. Fronto-temporal regions emerged as critical epicenters, showing both high nodal centrality and strong correlations with connected neighbors' thinning severity. We found that the individual differences in network-weighted cortical abnormality corresponded to clinical symptom variability, and distinguished two MUD biotypes associated with drug use. Our findings suggest that cortical thinning in MUD is influenced by the brain connectome architecture, providing a mechanistic framework for understanding individual variability in addiction progression.

Lower midlife physical activity is associated with higher risk of neurodegenerative disease in late life. However, it remains unknown whether physical exercise and fitness are associated with brain structural integrity during midlife. The purpose of this study was to compare brain structures between middle-aged aerobically trained adults (MA), middle-aged sedentary (MS), and young sedentary (YS) adults. Thirty MA (54±4 years), 30 MS (54±4 years), and 30 YS (32±6 years) participants (50% women) underwent measurements of brain volume, cortical thickness, and white matter (WM) fiber integrity using MRI. MA participants had aerobic training for 24.8±9.6 years and the highest cardiorespiratory fitness level (i.e., peak oxygen uptake: VO2peak) among all groups. Global WM integrity, as assessed with fractional anisotropy (FA) from diffusion tensor imaging, was lower in the MS compared with the YS group. However, global FA in the MA group was significantly higher than that in the MS group (P<0.05) and at a similar level to the YS group. Furthermore, tract-based spatial statistical analysis demonstrated that FA in the anterior, superior, and limbic WM tracts (e.g., the genu of the corpus callosum, superior longitudinal fasciculus, uncinate fasciculus) was higher in the MA compared with MS groups, and positively associated with VO2peak, independently from age and sex. From cortical thickness analysis, MS and MA participants showed thinner prefrontal and parieto-temporal areas than the YS group. On the other hand, the MA group exhibited thicker precentral, postcentral, pericalcarine, and lateral occipital cortices than the MS and YS groups. But, the insula and right superior frontal gyrus showed thinner cortical thickness in the MA compared with the MS groups. Collectively, these findings suggest that midlife aerobic exercise is associated with higher WM integrity and greater primary motor and somatosensory cortical thickness.

Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The -statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

DNA methylation influences gene-environment interactions and brain development in bipolar disorder (BD). We aimed to identify BD-associated epigenetic loci and examine their associations with brain structural variation. We conducted an epigenome-wide association study (BD group, n = 90; healthy controls group, n = 161) to identify BD-associated DNA methylation loci, and we additionally performed copy number alteration and functional enrichment analyses. The correlations between epigenetic loci and cortical thickness (CT) were assessed using Pearson's partial correlation analysis, and the co-methylation effect of the epigenetic loci identified in the neuroimaging-epigenetic analysis was investigated. A total of 156 differentially methylated positions (DMPs) and 7 differentially methylated regions were identified, and the genes associated with them were observed to be enriched in biological processes related to muscle hypertrophy and neuronal activity. Significant correlations between the methylation levels of 13 DMPs associated with three genes ( , , and ) and the CT of the right postcentral gyrus and inferior frontal gyrus were identified. Specifically, 10 DMPs associated with the CpG island in the upstream region of the gene showed negative correlations with the right postcentral gyrus CT, implicating -associated CpG-island methylation in regional cortical thinning. Epigenetic changes might play an important role in brain structural changes in BD. These multimodal findings nominate -related methylation as a candidate molecular correlate of cortical thinning and warrant replication and mechanistic follow-up in larger, state-diverse cohorts.

•Motor and visuospatial functions are predictors of social skills in IDD children.•Deviation from typical development of cortical thickness might impair cognition.•Fronto-parietal areas impact social skills via attention and visuospatial abilities.•Early visuospatial rehabilitation may improve social skills in IDD. Different theoretical perspectives emphasize the significance of sensorimotor and visuospatial functions in shaping social perception, including theory of mind (ToM) and affect recognition (AR) abilities. This study aimed to investigate where in the brain cortical thickness (CT) predicts social perception, and which cognitive functions mediate such relationship. To these aims, we used a hierarchical analytical plan: Step 1 identified brain areas’ CT that correlate with cognitive measures; Step 2 used stepwise regression to predict social perception outcomes (ToM and AR) from brain areas’ CT; Step 3 assessed whether cognitive measures mediate the link between CT and social perception outcomes. The results showed that the CT of the left inferior frontal gyrus (IFG; pars triangularis) predicted both ToM and AR, while the CT of the right superior parietal gyrus (SPL) and of the right anterior occipital sulcus (AOcs) predicted only AR. Mediation models unveiled that visuo-constructive abilities and visual attention mediated the relationship between CT in these areas and social perception outcomes. These findings align with the role of the IFG in mentalizing abilities and underscore the involvement of SPL in visuospatial functions, including mental object rotation and spatial perspective-taking, which are essential for advanced social skills; the role of the AOcs in face processing was also highlighted. Importantly, the findings suggest that fronto-parietal areas are indirectly involved in social perception thorough their involvement in visuo-constructive abilities and visual attention.

Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. Methods We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period. For this purpose, we leveraged longitudinal MRI data from 451 cognitively unimpaired participants (DELCODE; median age 69.71 [IQR 65.51, 75.50] years; 52.32% female). Participants underwent MRI sessions annually over a four-year period (1815 sessions in total, with roughly four MRI sessions per participant). We adjusted all models for demographics and cardiovascular risk. Results Our findings were three-fold. First, larger WMH volumes were linked to lower cortical thickness ( σ  = -0.165, SE  = 0.047, Z  = -3.515, P  < 0.001). Second, individuals with higher WMH volumes experienced more rapid cortical thinning ( σ  = -0.226, SE  = 0.093, Z  = -2.443, P  = 0.007), particularly in temporal, cingulate, and insular regions. Similarly, those with lower initial cortical thickness had faster WMH progression ( σ  = -0.141, SE  = 0.060, Z  = -2.336, P  = 0.009), with this effect being most pronounced in temporal, cingulate, and insular cortices. Third, faster WMH progression was associated with accelerated cortical thinning ( σ  = -0.239, SE  = 0.139, Z  = -1.710, P  = 0.044), particularly in frontal, occipital, and insular cortical regions. Conclusions Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable. Trial registration German Clinical Trials Register (DRKS00007966, 04/05/2015).

There is a growing body of evidence based on adult neuroimaging that suggests that the brain adapts to bilingual experiences to support language proficiency. The Adolescent Brain Cognitive Development (ABCD) Study is a useful source of data for evaluating this claim during childhood, as it involves data from a large sample of American children. Using the baseline ABCD Study data collected at ages nine and ten, the goal of this study was to identify differences in cortical thickness between bilinguals and monolinguals and to evaluate how variability in English vocabulary and English use within bilinguals might explain these group differences. We identified bilingual participants as children who spoke a non-English language and were exposed to the non-English language at home. We then identified a matched sample of English monolingual participants based on age, sex, pubertal status, parent education, household income, non-verbal IQ, and handedness. Bilinguals had thinner cortex than monolinguals in widespread cortical regions. Within bilinguals, more English use was associated with greater frontal and parietal cortical thickness; greater English vocabulary was associated with greater frontal and temporal cortical thickness. These findings replicate and extend previous research with bilingual children and highlight unexplained cortical thickness differences between bilinguals and monolinguals.