Sophia Frangou's research while affiliated with University of British Columbia - Vancouver and other places

Publications (368)

Preprint
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Mood and anxiety disorders typically begin in adolescence and have overlapping clinical features but marked inter-individual variation in clinical presentation. The use of multimodal neuroimaging data may offer novel insights into the underlying brain mechanisms. We applied Heterogeneity Through Discriminative Analysis (HYDRA) to measures of region...
Article
Bipolar disorder (BD) is a severe mental illness associated with alterations in brain organization. Neuroimaging studies have generated a large body of knowledge regarding brain morphological and functional abnormalities in BD. Current advances in the field have focussed on the need for more precise neuroimaging biomarkers. Here we present a select...
Article
Full-text available
Background: Major depressive disorder (MDD) is a polygenic disorder associated with brain alterations but until recently, there have been no brain-based metrics to quantify individual-level variation in brain morphology. Here, we evaluated and compared the performance of a new brain-based 'Regional Vulnerability Index' (RVI) with polygenic risk sc...
Article
Background There is significant heterogeneity in cognitive function in patients with bipolar I disorder (BDI); however, there is a dearth of research into biological mechanisms that might underlie cognitive heterogeneity, especially at disease onset. To this end, this study investigated the association between accelerated or delayed age-related bra...
Article
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Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface are...
Article
Full-text available
The brain-age-gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine-learning models to neuroimaging data and is considered a biomarker of brain health. Understanding sex differences in brainAGE is a significant step toward precision medicine. Global and local brainAGE (G-brainAGE and L-bra...
Article
Application of machine learning (ML) algorithms to structural magnetic resonance imaging (sMRI) data has yielded behaviorally meaningful estimates of the biological age of the brain (brain‐age). The choice of the ML approach in estimating brain‐age in youth is important because age‐related brain changes in this age‐group are dynamic. However, the c...
Article
Background: The COVID-19 pandemic has been associated with increased levels of depression and anxiety with implications for the use of antidepressant medications. Methods: The incident rate of antidepressant fills before and during the COVID-19 pandemic were compared using interrupted time-series analysis followed by comprehensive sensitivity an...
Article
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Background Accelerated aging has been proposed as a mechanism underlying the clinical and cognitive presentation of schizophrenia. The current study extends the field by examining both global and regional patterns of brain aging in schizophrenia, as inferred from brain structural data, and their association with cognitive and psychotic symptoms.Met...
Poster
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Introduction Cognitive symptoms are a common feature of schizophrenia (Kahn 2013), that are already present in the early stages of the illness. However, there is significant heterogeneity amongst patients with prior studies distinguishing two subgroups; one with cognitive impairment and another with preserved cognition (Wenzel 2021). Here, we repli...
Preprint
Mechanisms underpinning neurotypical age-related variations in cortical thickness in the human brain remain insufficiently specified. Here we used cell-specific marker genes, followed by gene ontology and enrichment analyses, to quantify the association between gene-expression levels and inter-regional age-related variations in neurotypical cortica...
Article
Objective: The study objective was to investigate the predictive value of functional connectivity changes induced by acute repetitive transcranial magnetic stimulation (rTMS) for clinical response in treatment-resistant depression. Methods: Cross-sectional changes in functional connectivity induced by a single concurrent rTMS-fMRI session were a...
Preprint
Eating disorders (ED) are psychiatric disorders with a neurobiological, psychological and socio-environmental basis. Specific neuropsychological and brain structure and function characteristics have been identified in ED. However, evidence has often relied on patients in the acute phase or recovered, precluding an understanding of whether such diff...
Article
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Background Metabolic dysregulation is currently considered a major risk factor for hippocampal pathology. The aim of the present study was to characterize the influence of key metabolic drivers on functional connectivity of the hippocampus in healthy adults. Methods Insulin resistance was directly quantified by measuring steady-state plasma glucos...
Article
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Background Global brainAGE predictions using structural MRI (i.e., deviation between neuroimaging-predicted and actual age) have shown accelerated aging in early psychosis (EP) patients, but are not informative about regional differences. Additionally, the link between brain-ageing and cognition in EP has not been addressed. Here, we used machine l...
Article
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Objective Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the l...
Preprint
Mechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 individuals, aged 4-89 years) depended on cell-specific ma...
Article
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Anorexia Nervosa has been associated with white matter abnormalities implicating subcortical abnormal myelination. Extending these findings to intracortical myelin has been challenging but ultra-high field neuroimaging offers new methodological opportunities. To test the integrity of intracortical myelin in AN we used 7 T neuroimaging to acquire T1...
Article
Anorexia Nervosa has been associated with white matter abnormalities implicating subcortical abnormal myelination. Extending these findings to intracortical myelin has been challenging but ultra‑high field neuroimaging offers new methodological opportunities. To test the integrity of intracortical myelin in AN we used 7 T neuroimaging to acquire T1...
Article
Full-text available
Background: Studies of COVID-19 pandemic biopsychosocial exposure and schizophrenia risk showed contradictory results, were undertaken early in the pandemic, and did not consider lockdowns or COVID-19 infection. Hence, we examined the association between COVID-19 biopsychosocial exposure and incident schizophrenia. Methods: An interrupted time-s...
Article
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Background One of the challenges in human neuroscience is to uncover associations between brain organization and psychopathology in order to better understand the biological underpinnings of mental disorders. Here, we aimed to characterize the neural correlates of psychopathology dimensions obtained using two conceptually different data-driven appr...
Preprint
Background The brain-age-gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine-learning models to neuroimaging data, and is considered a biomarker of brain health. Understanding sex-differences in brainAGE is a significant step toward precision medicine. Methods Global and local brainAGE...
Preprint
Full-text available
Schizophrenia is a chronic mental illness that is amongst the most debilitating conditions encountered in medical practice. A recent landmark schizophrenia study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This study -- and most...
Preprint
Full-text available
Application of machine learning algorithms to structural magnetic resonance imaging (sMRI) data has yielded behaviorally meaningful estimates of the biological age of the brain (brainage). The choice of the machine learning approach in estimating brain-age in children and adolescents is important because age-related brain changes in these age-group...
Article
Full-text available
Background To characterize the association between the protracted biopsychosocial coronavirus disease 2019 (COVID-19) pandemic exposures and incident suicide attempt rates. Methods Data were from a nationally representative cohort based on electronic health records from January 2013 to February 2021 ( N = 852 233), with an interrupted time series...
Poster
Our preliminary evidence suggest cognitive flexibility and aberrant functional connectivity as biomarkers for eating disorders.
Article
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Adolescence is a period of major brain reorganization shaped by biologically timed and by environmental factors. We sought to discover linked patterns of covariation between brain structural development and a wide array of these factors by leveraging data from the IMAGEN study, a longitudinal population-based cohort of adolescents. Brain structural...
Article
Background Aberrant emotion regulation has been posited as a putative endophenotype of bipolar disorder (BD). We therefore aimed to compare the neural responses during voluntary down-regulation of negative emotions in a large functional magnetic resonance imaging study of BD, patients' unaffected first-degree relatives (URs), and healthy controls (...
Article
Hippocampal integrity Is highly susceptible to metabolic dysfunction, yet its mechanisms are not well defined. We studied 126 healthy individuals aged 23-61 years. Insulin resistance (IR) was quantified by measuring steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Body mass index (BMI), adiposity, fasting insuli...
Article
Full-text available
Healthy aging is typically associated with some level of cognitive decline, but there is substantial variation in such decline among older adults. The mechanisms behind such heterogeneity remain unclear but some have suggested a role for cognitive reserve. In this work, we propose the “person-based similarity index” for cognition (PBSI-Cog) as a pr...
Chapter
Psychiatric disorders are brain disorders with high global prevalence that confer a significant personal and economic burden due to treatment costs, reduced productivity and increased morbidity and mortality. In the last three decades, neuroimaging has provided new tools and methods that enable the in vivo examination of brain organization in healt...
Article
Full-text available
Understanding sex-related differences across the human cerebral cortex is an important step in elucidating the basis of psychological, behavioural and clinical differences between the sexes. Prior structural neuroimaging studies primarily focused on regional sex differences using univariate analyses. Here we focus on sex differences in cortical mor...
Article
Brain-predicted age difference (brainPAD) has been used in schizophrenia to assess individual-level deviation in the biological age of the patients’ brain (i.e., brain-age) from normative reference brain structural datasets. There is marked inter-study variation in brainPAD in schizophrenia which is commonly attributed to sample heterogeneity. Howe...
Article
Full-text available
Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,07...
Article
Full-text available
Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resource...
Article
Full-text available
Background: Early psychosis in first-episode psychosis (FEP) and clinical high-risk (CHR) individuals has been associated with alterations in mean regional measures of brain morphology. Examination of variability in brain morphology could assist in quantifying the degree of brain structural heterogeneity in clinical relative to healthy control (HC...
Article
Full-text available
Objective: Suicide deaths and suicidal thoughts and behaviors are considered a public health emergency, yet their underpinnings in the brain remain elusive. The authors examined the classification accuracy of individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates, of suicidal thoughts and behaviors...
Article
Full-text available
Bipolar disorder (BD) and major depressive disorder (MDD) have both common and distinct clinical features, that pose both conceptual challenges in terms of their diagnostic boundaries and practical difficulties in optimizing treatment. Multivariate machine learning techniques offer new avenues for exploring these boundaries based on clinical neuroa...
Article
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Although previous studies have highlighted associations of cannabis use with cognition and brain morphometry, critical questions remain with regard to the association between cannabis use and brain structural and functional connectivity. In a cross‐sectional community sample of 205 African Americans (age 18–70) we tested for associations of cannabi...
Article
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Background and Purpose Source‐based morphometry(SBM) has been used in multicenter studies pooling magnetic resonance imaging data across different scanners to advance the reproducibility of neuroscience research. In the present study, we developed an analysis strategy for Scanner‐Specific Detection (SS‐Detect) of SBPs in multiscanner studies, and e...
Article
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Bipolar disorder and schizophrenia are associated with brain morphometry alterations. This study investigates inter-individual variability in brain structural profiles, both within diagnostic groups and between patients and healthy individuals. Brain morphometric measures from three independent samples of patients with schizophrenia ( n = 168), bip...
Article
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Abstract This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci as...
Article
Background Progress in precision psychiatry is predicated on identifying reliable individual-level diagnostic biomarkers. For psychosis, measures of structural and functional connectivity could be promising biomarkers given consistent reports of dysconnectivity across psychotic disorders using magnetic resonance imaging. Methods We leverage data f...
Article
Full-text available
Currently, several human brain functional atlases are used to define the spatial constituents of the resting-state networks (RSNs). However, the only brain atlases available are derived from samples of young adults. As brain networks are continuously reconfigured throughout life, the lack of brain atlases derived from older populations may inf luen...
Article
Full-text available
For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international da...
Presentation
There is good evidence that differences in executive function and functional connectivity at rest are present in individuals with eating disorders (ED) compared to healthy controls. However, we still do not know whether these anomalies are a consequence or precede ED. This is the first study to use the high-risk methodology (i.e. children born to m...
Poster
Full-text available
Myelin is a lipid-containing substance that coats axons enabling fast electrical impulse propagation. Cognitive functions rely on adequate axonal myelination. Few studies have investigated myelin abnormalities in patients with Anorexia nervosa (AN) using standard 3T MR scanners. In this preliminary study we aimed to examine intracortical myelin in...
Article
Full-text available
First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to co...
Article
Full-text available
Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early‐onset psychosis (mean...
Preprint
Full-text available
Background and Purpose Source-based morphometry (SBM) is a data-driven multivariate approach for interrogating covariation in structural brain patterns (SBPs) across subjects and quantifying the subject-specific loading parameters of these patterns. This approach has been used in multi-centre studies pooling magnetic resonance imaging (MRI) data ac...
Article
Full-text available
Background Adolescence is a critical developmental stage. A key challenge is to characterize how variation in adolescent brain organization relates to psychosocial and environmental influences. Methods We used canonical correlation analyses to discover distinct patterns of covariation between measures of brain organization (brain morphometry, intr...
Article
Full-text 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...
Preprint
Full-text available
Background: Schizophrenia has been associated with lifelong deviations in the normative trajectories of brain structure. These deviations can be captured using the brain-predicted age difference (brainPAD), which is the difference between the biological brain age of an individual, as inferred from neuroimaging data, and their chronological age. Var...
Preprint
Full-text available
Currently, several human brain functional atlases are used to define the spatial constituents of the resting-state networks (RSNs). However, the only brain atlases available are derived from samples of young adults. As brain networks are continuously reconfigured throughout life, the lack of brain atlases derived from older populations may influenc...
Article
Full-text available
BACKGROUND Bipolar disorder shows significant variability in clinical presentation. Here we adopt a personalized approach to quantify the brain structural and functional similarity of each individual patient to other patients and to healthy individuals. METHODS Brain morphometric and resting-state functional connectivity measures from two independ...
Article
Full-text available
Background.: The default mode network (DMN) dysfunction has emerged as a consistent biological correlate of multiple psychiatric disorders. Specifically, there is evidence of alterations in DMN cohesiveness in schizophrenia, mood and anxiety disorders. The aim of this study was to synthesize at a fine spatial resolution the intra-network functiona...
Article
Full-text available
Background.: The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is cur...
Preprint
Full-text available
Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalised on the resource...
Preprint
Full-text available
Delineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thi...
Article
Background: Chronological age can be accurately predicted using machine learning analysis of MRI data. Discrepancies between MRI-predicted and actual age have been interpreted in terms of delayed maturation (negative brain age gap) or accelerated ageing (positive brain age gap). Here we test whether such brain age gaps are associated with cognitive...