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23 results

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  • 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
  • Journal: Psychological Medicine / Volume 53 / Issue 10 / July 2023
  • Published online by Cambridge University Press: 07 July 2022, pp. 4707-4719
  • Print publication: July 2023
  • 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.

    Methods

    Forty-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.

    Results

    Individuals 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.

    Conclusions

    We 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.

  • Individualized risk components guiding antipsychotic delivery in patients with a clinical high risk of psychosis: application of a risk calculator

  • TianHong Zhang, LiHua Xu, HuiJun Li, HuiRu Cui, YingYing Tang, YanYan Wei, XiaoChen Tang, YeGang Hu, Li Hui, ChunBo Li, Margaret A. Niznikiewicz, Martha E. Shenton, Matcheri S. Keshavan, William S. Stone, JiJun Wang
  • Journal: Psychological Medicine / Volume 52 / Issue 15 / November 2022
  • Published online by Cambridge University Press: 17 February 2021, pp. 3412-3421
  • Print publication: November 2022
  • Background

    Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics.

    Methods

    Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher).

    Results

    In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment.

    Conclusions

    Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

  • Calculating individualized risk components using a mobile app-based risk calculator for clinical high risk of psychosis: findings from ShangHai At Risk for Psychosis (SHARP) program

  • TianHong Zhang, LiHua Xu, HuiJun Li, Kristen A. Woodberry, Emily R. Kline, Jian Jiang, HuiRu Cui, YingYing Tang, XiaoChen Tang, YanYan Wei, Li Hui, Zheng Lu, LiPing Cao, ChunBo Li, Margaret A. Niznikiewicz, Martha E. Shenton, Matcheri S. Keshavan, William S. Stone, JiJun Wang
  • Journal: Psychological Medicine / Volume 51 / Issue 4 / March 2021
  • Published online by Cambridge University Press: 16 December 2019, pp. 653-660
  • Print publication: March 2021
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  • Background

    Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program.

    Method

    In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC.

    Results

    The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal.

    Conclusions

    The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.

  • A comparison of clinical and linguistic indices of deviance in the verbal discourse of schizophrenics

  • Lynne M. Sanders, Jane Adams, Helen Tager-Flusberg, Martha E. Shenton, Michael Coleman
  • Journal: Applied Psycholinguistics / Volume 16 / Issue 3 / July 1995
  • Published online by Cambridge University Press: 21 March 2016, pp. 325-338

  • The goal of this study was to compare clinical and psycholinguistic approaches to the measurement of verbal behavior according to their ability to discriminate schizophrenic (n = 11) from manic-depressive (n = 11) and normal control (n = 11) subjects. Language samples were obtained during Rorschach testing and analyzed using a clinical measure, the Thought Disorder Index (TDI), and a battery of linguistic measures. Five linguistic categories were examined: productivity, repetition, dysfluency, cohesiveness, and syntactic complexity. On the clinical measure, schizophrenic subjects had high thought disorder scores. On the linguistic measures, the speech of schizophrenics differed significantly from the other two groups in productivity and in the number of clearly referenced elements, a measure of cohesion. This measure of cohesion was positively correlated with TDI scores. The findings are discussed in terms of the benefits of using more objective and quantitative measurements in research on thought disorganization in schizophrenia.

  • Multimodal Imaging in Psychiatry: The Electroencephalogram as a Complement to Other Modalities

  • Dean F. Salisbury, Brian F. O'Donnell, Paul G. Nestor, Martha E. Shenton, Robert W. McCarley
  • Journal: CNS Spectrums / Volume 4 / Issue 8 / August 1999
  • Published online by Cambridge University Press: 07 November 2014, pp. 44-57

  • The use of different imaging modalities provides the clinician and researcher with different views of anatomy and physiology at unprecedented levels of detail. Multimodal imaging allows for noninvasive measurement of structure and function in humans during complex behavior, and thus provides information about the inner workings of the brain previously unavailable. The present paper examines the various imaging techniques available, and describes their application to the clinic—in the case of epilepsy—and to research—in the case of schizophrenia. Because the electroen-cephalogram has a dynamic response in milliseconds, it provides the best temporal sensitivity of functional measures of brain activity. When coupled with high-resolution magnetic resonance imaging measures of brain structure, this multimodal approach provides a powerful tool for understanding brain activity. Clinically, the use of multimodal imaging has provided greater precision in localization of the epileptogenic focus. For researchers attempting to determine the underlying causes of schizophrenia, the use of multimodal imaging has helped lead the field away from a specific lesion view to a more distributed system abnormality view of this disorder.

  • Section I - Schizophrenia

  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp -

  • Summary

    This chapter provides a review of the vast body of published research that has used either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI) to investigate for neuroanatomical abnormalities in schizophrenia (SZ) patients. If one thing is clear from the multitude of MRI and DTI studies reviewed in the chapter, it is that there is now a great deal of evidence indicating that SZ patients exhibit consistent (albeit subtle) and widespread abnormalities in both their gray matter (GM) and white matter (WM). An important question, then, is whether these GM and WM abnormalities have separate causes, or whether they share a common underlying pathology. A highly speculative theory is presented as to how a single mechanism could potentially underlie the GM abnormalities, WM abnormalities, hyperdopaminergia and psychotic features characteristic of SZ. This theory is extremely speculative and would benefit from a great deal more supporting empirical evidence.

  • Section VII - Developmental Disorders

  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp -

  • Summary

    This chapter reviews magnetic resonance imaging (MRI) findings on developmental disabilities that arise from both modular and distributed perspectives on brain function, although the former clearly represent the majority of existing data. It focuses exclusively on autism spectrum disorders (ASD) including the diagnoses of autism, Asperger's Syndrome, and pervasive developmental disorder. Some evidence indicates that observed abnormalities in language areas may reflect different processing styles, rather than deficits per se. Visual information processing has always been a topic of great interest to ASD researchers, as individuals with ASD often show preserved and sometimes enhanced visual abilities. A large number of studies have established the role of superior temporal sulcus in various aspects of social perception. Mirror neuron system (MNS) has proven responsive to both the perception and implementation of specific body movements. The relatively high spatial resolution of MRI lends itself very well to the isolation of specific brain structures.

  • Section IV - Cognitive Disorders

  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp -

  • Summary

    The computational anatomy techniques enable us to detect and to visualize discrete changes in cortical and hippocampal integrity and to track the spread of Alzheimer's disease (AD) pathology throughout the living brain. This chapter focuses on the new generation of cortical and hippocampal mapping techniques, while reviewing the research findings reported in the literature. The computational anatomy field is based on mathematical approaches for modeling anatomical structures in brain images. 3D surface-based analyses have documented the relentless progression of AD pathology-driven changes from pre-dementia of the Alzheimer's type (DAT) to moderate DAT. An important utility of the cortical mapping approaches is the exploration of brain-behavior correlations. For decades, DAT clinical trial design has relied solely on cognitive and functional outcome measures. A major advantage of computational anatomy techniques is to track the disease process in 3D, revealing the dynamic sequence in which brain structures are affected.

  • Preface

    • By Martha E. Shenton, VA Boston Healthcare System and Department of Psychiatry Brigham and Women's Hospital Harvard Medical School Boston, MA, USA, Bruce I. Turetsky, Department of Psychiatry University of Pennsylvania School of Medicine Philadelphia, PA, USA
  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp xiii-xiv

  • Summary

    Historically, the opportunity to examine the inner workings of the human body was limited to the study of cadavers. In the past 30 years, medical imaging technology has provided researchers with a new window into the living human body. Advances in medical imaging technology have, in fact, truly revolutionized nearly every area of medicine. These advances include both dramatic improvements in image resolution and the development of novel imaging techniques, from computed axial tomography (CT), to positron emission tomography (PET), to single photon emission tomography (SPECT), to magnetic resonance imaging (MRI), including fMRI (functional MRI) and diffusion tensor imaging (DTI), to magnetic resonance spectroscopy (MRS), ultrasound, and magnetoencephalography (MEG) – all of which provide an unprecedented view, in exquisite detail, of anatomical structures and/or functions in the living human body.

    One medical discipline that has been in the forefront of this revolution is neuropsychiatry (defined here as encompassing both psychiatry and behavioral neurology), where novel neuroimaging tools have been developed and applied to neuropsychiatric disorders in order to understand further the neuroanatomical and neurophysiological bases of mental illnesses and cognitive disorders, including Alzheimer's and Parkinson's diseases.

    This book reviews important new findings about the role of brain abnormalities in neuropsychiatric disorders based on this new imaging technology. In considering the progress in this area, it is clear that initially the quest was to identify and characterize focal brain abnormalities in an effort to delineate further various psychiatric and neuropsychiatric syndromes.

  • 1 - Structural imaging of schizophrenia

  • from Section I - Schizophrenia
    • 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
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp 1-29

  • 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.

Understanding Neuropsychiatric Disorders
  • Insights from Neuroimaging
  • Edited by Martha E. Shenton, Bruce I. Turetsky
  • Published online: 10 January 2011
  • Print publication: 09 December 2010
  • An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.

  • Section VI - Eating Disorders

  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp -

  • Summary

    The conceptual framework of the pathophysiology and etiology of the eating disorders (EDs) anorexia nervosa (AN), bulimia nervosa (BN) as well as the emerging ED binge eating disorder (BED), has undergone significant changes in the past few decades. Structural imaging techniques such as computer tomography (CT) and radiation-free magnetic resonance imaging (MRI) provide information on gross structural abnormalities. Quantitative electroencephalography (qEEG) studies have recently come to prominence as a functional assessment method. Functional brain imaging is performed in conjunction with paradigms and tasks that are meant to elicit areas of brain activation that might be specific for AN pathophysiology. Many different paradigms have been used over the past years, with positron emission tomography (PET) and single photon emission computed tomography (SPECT) comprising the earlier work and functional MRI achieving prominence more recently. A mixed group of AN and BN subjects had reduced prefrontal myo-inositol and lipid compounds compared to controls.

  • Section V - Substance Abuse

  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp -

  • Summary

    Alcoholism is frequently accompanied by comorbidities of drugs of abuse and psychiatric diseases. For example, individuals with schizophrenia are at increased risk for developing substance abuse disorders. The availability of imaging tools has enhanced the appreciation of the effects of chronic and excessive alcohol exposure on the human brain. In-vivo computerized tomography (CT) and magnetic resonance imaging (MRI) studies of alcoholism complement postmortem neuropathological investigations in the search for structural brain abnormalities due to alcoholism. This chapter first reviews the general principles of brain imaging and of images analyses as they pertain to the characterization of appropriate structural regions. Then, it reviews the literature on the effects of alcoholism on brain structure as revealed by brain imaging. In combination with structural imaging, experimental models of alcoholism could be a translational point in identifying mechanisms of alcohol-related brain dysmorphology.

  • Section III - Anxiety Disorders

  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp -

  • Summary

    Post-traumatic stress disorder (PTSD) includes a constellation of disabling behavioral and emotional symptoms that occur in a proportion of individuals exposed to severe psychological trauma. This chapter reviews the structural neuroimaging findings pertaining to specific brain regions in adults with PTSD. Although the majority of adult neuroimaging reports have centered on the hippocampus, medial prefrontal cortex, and amygdala, structural studies are potential abnormalities in other brain regions as well. The cavum septum pelucidum (CSP), a small cerebrospinal fluid filled cleft in the anterior portion of the septo-callosal junction, has been found to exist with greater frequency in individuals diagnosed with PTSD. Pediatric studies of PTSD have not fully replicated findings reported in the adult literature, and suggest that the neuroanatomical correlates of PTSD may manifest in a more generalized manner in children and adolescents who are traumatized.

  • Section II - Mood Disorders

  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Published online: 10 January 2011
  • Print publication: 09 December 2010, pp -

  • Summary

    This chapter discusses recent structural neuroimaging studies that address the regions of interest in the proposed anterior limbic network model. Given the predominance of MRI in structural imaging of psychiatric disorders, the chapter also focuses on this imaging modality. First, longitudinal studies are needed to clarify how brain structures change within individual patients, with particular regard to the corresponding course of illness. Second, more sophisticated measures, such as diffusion tensor imaging (DTI) tractography or shape analyses, may more consistently define the subtle structural abnormalities that are likely in bipolar disorder and that may be missed with less-specific measures. Third, studies in young patients are critical given the typical adolescent onset of bipolar disorder and early course progression. Finally, integrating structural imaging with functional and neurochemical are the only ways to move morphometric imaging from high-priced and sophisticated phrenology to a better understanding of the neural basis of bipolar disorder.

  • The effect of background noise on P300 to suprathreshold stimuli

  • DEAN F. SALISBURY, MASSIMO A. DESANTIS, MARTHA E. SHENTON, ROBERT W. MCCARLEY
  • Journal: Psychophysiology / Volume 39 / Issue 1 / January 2002
  • Published online by Cambridge University Press: 08 June 2017, pp. 111-115
  • Print publication: January 2002

  • Both the amplitude and latency of P300 vary with changes in stimulus parameters. Stimuli at intensities or pitch separations near threshold evoke a smaller and later P300. P300 is also affected by extraneous stimulus parameters in tasks where stimulus frequency separation is large and stimuli are well above intensity thresholds. For example, the presence of background white noise when tones are suprathreshold and easily detectable has been reported to increase P300 latency. However, the effects of background masking noise on P300 amplitude and scalp topography have not been reported. Subjects performed an oddball task both in the presence and in the absence of background noise. Performance accuracy was unaffected by background noise. P300 showed latency increases when noise was present, but P300 peak amplitude was unaffected. P300 scalp topography was stable across both conditions. P300 latency is affected by background noise, even when performance is not, but amplitude and amplitude topography remain unaffected.

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