4 results
Shared and distinct white matter abnormalities in adolescent-onset schizophrenia and adolescent-onset psychotic bipolar disorder
- Johanna Seitz-Holland, Felix L. Nägele, Marek Kubicki, Ofer Pasternak, Kang Ik K. Cho, Morgan Hough, Christoph Mulert, Martha E. Shenton, Timothy J. Crow, Anthony C. D. James, Amanda E. Lyall
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- Journal:
- Psychological Medicine / Volume 53 / Issue 10 / July 2023
- Published online by Cambridge University Press:
- 07 July 2022, pp. 4707-4719
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Background
While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need.
MethodsForty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence.
ResultsIndividuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age.
ConclusionsWe observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.
Reduced limbic microstructural integrity in functional neurological disorder
- Ibai Diez, Benjamin Williams, Marek R. Kubicki, Nikos Makris, David L. Perez
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- Journal:
- Psychological Medicine / Volume 51 / Issue 3 / February 2021
- Published online by Cambridge University Press:
- 26 November 2019, pp. 485-493
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Background
Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration.
MethodsA diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons.
ResultsCompared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients.
ConclusionsIn this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.
Neuroimaging auditory verbal hallucinations in schizophrenia patient and healthy populations
- Maria Angelique Di Biase, Fan Zhang, Amanda Lyall, Marek Kubicki, René C. W. Mandl, Iris E. Sommer, Ofer Pasternak
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- Journal:
- Psychological Medicine / Volume 50 / Issue 3 / February 2020
- Published online by Cambridge University Press:
- 14 February 2019, pp. 403-412
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Background
Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers.
MethodsDiffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan–Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls.
ResultsCompared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (<40 years) H-AVH and SCZ-AVH subjects displayed overlapping FA deficits across four regions (p < 0.05): the genu and splenium of the corpus callosum, as well as the anterior limbs of the internal capsule. Analyzing these regions with free-water imaging ascribed overlapping FA abnormalities to tissue-specific anisotropy changes.
ConclusionsWe identified white matter pathology associated with the presence of AVH, independent of diagnostic status. However, commonalities were constrained to younger and more homogenous groups, after reducing pathologic variance associated with advancing age and chronicity effects.
1 - Structural imaging of schizophrenia
- from Section I - Schizophrenia
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- By Thomas J. Whitford, Department of Psychiatry Brigham and Women's Hospital Harvard School of Medicine Boston, MA, USA and Department of Psychiatry Melbourne Neuropsychiatry Centre University of Melbourne Melbourne, Australia, Marek Kubicki, Department of Psychiatry VA Boston Healthcare System and Department of Psychiatry Brigham and Women's Hospital Harvard Medical School Boston, MA, USA, Martha E. Shenton, VA Boston Healthcare System and Department of Psychiatry Brigham and Women's Hospital Harvard Medical School Boston, MA, USA
- Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
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- Book:
- Understanding Neuropsychiatric Disorders
- Published online:
- 10 January 2011
- Print publication:
- 09 December 2010, pp 1-29
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Summary
Introduction
Emil Kraepelin, one of the founding fathers of the diagnostic concept of schizophrenia, argued that the disorder was underpinned by abnormalities in brain structure. In his 1899 textbook, Kraepelin wrote: “in dementia praecox [schizophrenia], partial damage to, or destruction of, cells of the cerebral cortex must probably occur” (Kraepelin,1907). Since that time, an enormous amount of research has been undertaken with an eye to determining whether or not Kraepelin was correct. Until recently, the question of whether patients with schizophrenia (SZ) exhibit abnormalities in brain structure was more or less synonymous with the question of whether they exhibit abnormalities in gray matter (GM). The GM, so-called because of its grayish appearance in post-mortem tissue sections, is thought to consist primarily of neuron bodies, dendrites, axon terminals and other synaptic infrastructure and certain classes of neuroglia. Until recently, the vast majority of research aimed at investigating the neuroanatomical underpinnings of SZ has focused on GM. This is perhaps understandable, given that GM comprises both the brain's fundamental units of information processing (neurons) and the sites-of-action for most psychotropic medications (synapses). In recent years, however, a growing proportion of contemporary research has begun to focus on the “other half of the brain” (as wryly denoted by Fields, 2004), i.e. the white matter. The white matter (WM) is primarily constituted of myelinated axon sheaths, which form the infrastructure for signal transmission between spatially discrete populations of neurons.