Publications by authors named "Edward Bullmore"

Although both central and peripheral inflammation have been observed consistently in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression.

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Recent advances in structural MRI analytics now allow the network organization of individual brains to be comprehensively mapped through the use of the biologically principled metric of anatomical similarity. In this Review, we offer an overview of the measurement and meaning of structural MRI similarity, especially in relation to two key assumptions that often underlie its interpretation: (i) that MRI similarity can be representative of architectonic similarity between cortical areas and (ii) that similar areas are more likely to be axonally connected, as predicted by the homophily principle. We first introduce the historical roots and technical foundations of MRI similarity analysis and compare it with the distinct MRI techniques of structural covariance and tractography analysis.

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Introduction: Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis-C virus (HCV) infection. Though clinically effective, IFN-α frequently induces functionally impairing mood and motivation symptoms, particularly fatigue. Unlike mood impairment, which typically emerges after weeks of treatment, fatigue tends to emerge and evolve rapidly, typically within hours of the first IFN-α injection.

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Article Synopsis
  • Post-mortem studies reveal that patients who died from COVID-19 often show brainstem damage, which may result from immune responses during and after the infection.
  • Symptoms such as fatigue, breathlessness, and chest pain in post-hospitalization COVID-19 patients may be linked to these brainstem abnormalities.
  • Using advanced MRI techniques, a study found increased susceptibility in key brainstem regions of COVID-19 survivors, indicating a correlation between these changes and the severity of their illness and recovery outcomes.
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Background: The Choroid Plexus (ChP) plays a vital role in brain homeostasis, serving as part of the Blood-Cerebrospinal Fluid Barrier, contributing to brain clearance pathways and being the main source of cerebrospinal fluid. Since the involvement of ChP in neurological and psychiatric disorders is not entirely established and currently under investigation, accurate and reproducible segmentation of this brain structure on large cohorts remains challenging. This paper presents ASCHOPLEX, a deep-learning tool for the automated segmentation of human ChP from structural MRI data that integrates existing software architectures like 3D UNet, UNETR, and DynUNet to deliver accurate ChP volume estimates.

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Transcriptomic profiles are important indicators for molecular mechanisms and pathways involved in major depressive disorder (MDD) and its different phenotypes, such as immunometabolic depression. We performed whole-transcriptome and pathway analyses on 139 individuals from the observational, case-control, BIOmarkers in DEPression (BIODEP) study, 105 with MDD and 34 controls. We divided MDD participants based on levels of inflammation, as measured by serum high-sensitivity C-reactive protein (CRP), in n = 39 'not inflamed' (CRP < 1 mg/L), n = 31 with 'elevated CRP' (1-3 mg/L), and n = 35 with 'low-grade inflammation' (>3 mg/L).

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The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown.

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Article Synopsis
  • Chronic social defeat (CSD) stress in mice leads to a significant accumulation of neutrophils in the meningeal area, while acute stress does not have the same effect.
  • The study utilizes various techniques, like cytometry and single-cell sequencing, to show that CSD increases neutrophil movement from bone marrow through vascular channels.
  • Blocking type I interferon (IFN-I) signaling can prevent negative behaviors linked to CSD stress, suggesting that targeting this pathway could help develop new treatments for stress-related disorders.
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We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (n = 34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bimodal distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex, and complex sulci were less heritable and typically located in heteromodal cortex.

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  • Autism and ADHD are complex neurodevelopmental disorders with overlapping features, but they are rarely studied together, especially regarding sex differences.
  • The study utilized a large neuroimaging dataset to analyze cortical anatomy linked to autism and ADHD, revealing specific patterns in brain structure for each condition.
  • Findings showed that autism presented with greater cortical thickness in specific areas, while ADHD had more global increases in thickness but lower volume and surface area; also, unique patterns were observed in individuals with both conditions.
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  • The study investigates how the brain’s structural and functional networks develop during adolescence, highlighting the importance of these changes for adult cognitive and emotional outcomes.
  • It analyzes MRI data from 300 healthy adolescents to create morphometric similarity networks (MSNs), revealing increased similarity in paralimbic areas (like the insula) but decreased similarity in neocortical areas as adolescence progresses.
  • Findings suggest that while neocortical areas become more functionally integrated and distinct (often linked to processes like thinning and myelination), paralimbic areas focus on affective functions and show less differentiation during this critical developmental period.
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Adolescence is a period of dynamic brain remodeling and susceptibility to psychiatric risk factors, mediated by the protracted consolidation of association cortices. Here, we investigated whether longitudinal variation in adolescents' resilience to psychosocial stressors during this vulnerable period is associated with ongoing myeloarchitectural maturation and consolidation of functional networks. We used repeated myelin-sensitive Magnetic Transfer (MT) and resting-state functional neuroimaging (n = 141), and captured adversity exposure by adverse life events, dysfunctional family settings, and socio-economic status at two timepoints, one to two years apart.

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Article Synopsis
  • - The study investigates how major depressive disorder (MDD) affects brain structure and cognitive function, particularly looking at how these changes relate to normal brain development and aging in adolescents and adults.
  • - Researchers analyzed brain data from 304 participants with MDD and 236 without, finding that individuals with MDD had lower brain centile scores, indicating atypical brain aging, and those scores were linked to working memory only in the control group.
  • - The findings suggest that MDD is associated with unusual brain development and aging, but severity of depression and childhood maltreatment did not significantly influence brain measurements or treatment responses.
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Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence.

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Childhood maltreatment (CM) leads to a lifelong susceptibility to mental ill-health which might be reflected by its effects on adult brain structure, perhaps indirectly mediated by its effects on adult metabolic, immune, and psychosocial systems. Indexing these systemic factors via body mass index (BMI), C-reactive protein (CRP), and rates of adult trauma (AT), respectively, we tested three hypotheses: (H1) CM has direct or indirect effects on adult trauma, BMI, and CRP; (H2) adult trauma, BMI, and CRP are all independently related to adult brain structure; and (H3) childhood maltreatment has indirect effects on adult brain structure mediated in parallel by BMI, CRP, and AT. Using path analysis and data from = 116,887 participants in UK Biobank, we find that CM is related to greater BMI and AT levels, and that these two variables mediate CM's effects on CRP [H1].

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Sex hormones have biological effects on inflammation, and these might contribute to the sex-specific features of depression. C-reactive protein (CRP) is the most widely used inflammatory biomarker and consistent evidence shows a significant proportion (20-30 %) of patients with major depressive disorder (MDD) have CRP levels above 3 mg/L, a threshold indicating at least low-grade inflammation. Here, we investigate the interplay between sex hormones and CRP in the cross-sectional, observational Biomarkers in Depression Study.

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We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (N=34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bipolar distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex; complex sulci were less heritable and typically located in heteromodal cortex.

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Background: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Normative modelling provides a unified framework for studying age-specific and sex-specific divergences in neurodivergent brain development.

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Genetic risks for schizophrenia are theoretically mediated by genetic effects on brain structure but it has been unclear which genes are associated with both schizophrenia and cortical phenotypes. We accessed genome-wide association studies (GWAS) of schizophrenia (N = 69,369 cases; 236,642 controls), and of three magnetic resonance imaging (MRI) metrics (surface area, cortical thickness, neurite density index) measured at 180 cortical areas (N = 36,843, UK Biobank). Using Hi-C-coupled MAGMA, 61 genes were significantly associated with both schizophrenia and one or more MRI metrics.

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Background Clinically acquired brain MRI scans represent a valuable but underused resource for investigating neurodevelopment due to their technical heterogeneity and lack of appropriate controls. These barriers have curtailed retrospective studies of clinical brain MRI scans compared with more costly prospectively acquired research-quality brain MRI scans. Purpose To provide a benchmark for neuroanatomic variability in clinically acquired brain MRI scans with limited imaging pathology (SLIPs) and to evaluate if growth charts from curated clinical MRI scans differed from research-quality MRI scans or were influenced by clinical indication for the scan.

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The relationship between obesity and human brain structure is incompletely understood. Using diffusion-weighted MRI from ∼30,000 UK Biobank participants, we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal/temporal/striatal system associated with ISOVF and a medial temporal/occipital/striatal system associated with ICVF.

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Autism presents with significant phenotypic and neuroanatomical heterogeneity, and neuroimaging studies of the thalamus, globus pallidus and striatum in autism have produced inconsistent and contradictory results. These structures are critical mediators of functions known to be atypical in autism, including sensory gating and motor function. We examined both volumetric and fine-grained localized shape differences in autism using a large (=3145, 1045-1318 after strict quality control), cross-sectional dataset of T1-weighted structural MRI scans from 32 sites, including both males and females (assigned-at-birth).

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Article Synopsis
  • The study examined the genetic basis of various structural features of the human cerebral cortex using data from over 36,000 individuals and identified 4,349 significant genetic locations linked to cortical traits.
  • Researchers explored 13 different phenotypes, including thickness, surface area, and water diffusion, and found four genetic structures that suggest different developmental gene expression paths.
  • The findings highlight complex relationships among the identified phenotypes and suggest that genetic variants related to cortical expansion may also be linked to certain head disorders, emphasizing the genetic organization of the cortex and its developmental implications.
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Childhood adversity is one of the strongest predictors of adolescent mental illness. Therefore, it is critical that the mechanisms that aid resilient functioning in individuals exposed to childhood adversity are better understood. Here, we examined whether resilient functioning was related to structural brain network topology.

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Structural similarity is a growing focus for magnetic resonance imaging (MRI) of connectomes. Here we propose Morphometric INverse Divergence (MIND), a new method to estimate within-subject similarity between cortical areas based on the divergence between their multivariate distributions of multiple MRI features. Compared to the prior approach of morphometric similarity networks (MSNs) on n > 11,000 scans spanning three human datasets and one macaque dataset, MIND networks were more reliable, more consistent with cortical cytoarchitectonics and symmetry and more correlated with tract-tracing measures of axonal connectivity.

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