Psychiatry - Research Publications
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ItemMachine Learning for Large-Scale Quality Control of 3D Shape Models in Neuroimaging(SPRINGER INTERNATIONAL PUBLISHING AG, 2017)As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.
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ItemChildhood adversity impacts on brain subcortical structures relevant to depression(PERGAMON-ELSEVIER SCIENCE LTD, 2017-03)Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression.
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ItemCortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium(ELSEVIER SCIENCE INC, 2018-11-01)BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.
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ItemCortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group(NATURE PUBLISHING GROUP, 2017-06)The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
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ItemNeurodevelopmental correlates of the emerging adult self(ELSEVIER SCI LTD, 2019-04)The self-concept - the set of beliefs that a person has about themselves - shows significant development from adolescence to early adulthood, in parallel with brain development over the same period. We sought to investigate how age-related changes in self-appraisal processes corresponded with brain network segregation and integration in healthy adolescents and young adults. We scanned 88 participants (46 female), aged from 15 to 25 years, as they performed a self-appraisal task. We first examined their patterns of activation to self-appraisal, and replicated prior reports of reduced dorsomedial prefrontal cortex activation with older age, with similar reductions in precuneus, right anterior insula/operculum, and a region extending from thalamus to striatum. We used independent component analysis to identify distinct anterior and posterior components of the default mode network (DMN), which were associated with the self-appraisal and rest-fixation parts of the task, respectively. Increasing age was associated with reduced functional connectivity between the two components. Finally, analyses of task-evoked interactions between pairs of nodes within the DMN identified a subnetwork that demonstrated reduced connectivity with increasing age. Decreased network integration within the DMN appears to be an important higher-order maturational process supporting the emerging adult self.
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ItemNeuroimaging predictors of onset and course of depression in childhood and adolescence: A systematic review of longitudinal studies(ELSEVIER SCI LTD, 2019-10)Major depressive disorder (MDD) often emerges during adolescence with detrimental effects on development as well as lifetime consequences. Identifying neurobiological markers that are associated with the onset or course of this disorder in childhood and adolescence is important for early recognition and intervention and, potentially, for the prevention of illness onset. In this systematic review, 68 longitudinal neuroimaging studies, from 34 unique samples, that examined the association of neuroimaging markers with onset or changes in paediatric depression published up to 1 February 2019 were examined. These studies employed different imaging modalities at baseline; structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI) or electroencephalography (EEG). Most consistent evidence across studies was found for blunted reward-related (striatal) activity (fMRI and EEG) as a potential biological marker for both MDD onset and course. With regard to structural brain measures, the results were highly inconsistent, likely caused by insufficient power to detect complex mediating effects of genetic and environmental factors in small sample sizes. Overall, there were a limited number of samples, and confounding factors such as sex and pubertal development were often not considered, whereas these factors are likely to be relevant especially in this age range.
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ItemHuman subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex(SPRINGER, 2017-10)The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.
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ItemNovel genetic loci associated with hippocampal volume(NATURE PUBLISHING GROUP, 2017-01-18)The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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ItemNo Preview AvailableBrain Structural Signatures of Adolescent Depressive Symptom Trajectories: A Longitudinal Magnetic Resonance Imaging Study(ELSEVIER SCIENCE INC, 2017-07)OBJECTIVE: Most evidence for structural brain abnormalities associated with adolescent depression is based on cross-sectional study designs that do not take into account the dynamic course of depressive symptoms and brain maturation across adolescence. In this study, a longitudinal design was used to investigate the association between different trajectories of depressive symptoms and longitudinal changes in brain structure throughout adolescence. METHOD: One hundred forty-nine adolescents were assessed on depressive symptoms and underwent structural magnetic resonance imaging at 12 years of age and were followed up multiple times until 19 years. Three depressive symptom trajectories (low-stable [n = 97], early-decreasing [n = 33], late-increasing [n = 19]) were identified, and effects of group and group by time on hippocampus and amygdala volume and prefrontal cortical thickness and surface area were evaluated. RESULTS: The early-decreasing symptoms group exhibited differences in cortical surface area compared to the low-stable and late-increasing symptoms groups, moderated by sex. Specifically, females in the early-decreasing symptoms group showed lower anterior cingulate and orbitofrontal cortex surface areas across adolescence compared to females in the other groups. Males in the early-decreasing symptoms group showed lower right orbitofrontal cortex surface area expansion over time compared to males in the low-stable and late-increasing symptoms groups. No effects were found for cortical thickness or for hippocampus and amygdala volume. CONCLUSION: Alterations in cortical surface area were specifically observed in young people experiencing depressive symptoms in early adolescence. These findings suggest that early adolescence is a particularly sensitive period for cortical surface area abnormalities associated with depressive symptoms and could provide a critical window for treatment of (subthreshold) depressive symptoms.