Brain Abnormalities in Schizophrenia

11 Key excerpts on "Brain Abnormalities in Schizophrenia"

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  eBook - ePub

  Controversies in Schizophrenia

  Issues, Causes, and Treatment

  • Michael Farrell(Author)
  • 2023(Publication Date)
  • Routledge

    (Publisher)

  6 Brain Anomalies in Schizophrenia

  DOI: 10.4324/9781003413554-6

  Introduction

  This chapter firstly summarise points emerging from orthodox and dissenting positions. These concern brain anomalies in some people with schizophrenia, and whether schizophrenia is a brain disorder. I discuss imaging techniques like computerised tomography (CT) or magnetic resonance imagery (MRI) scans which indicate structural and functional brain anomalies in people with schizophrenia. These have been studied through repeated assessments at different stages of the disorder. Structural deficits include reduced grey matter volume, and the disruption of the integrity of white matter. Among functional anomalies identified have been abnormal neural activity when people with schizophrenia engage in certain cognitive tasks for example involving long and short-term memory. Specific parts of the brain have been related to changes, such as enlargement of the lateral ventricles, and reduction of the hippocampus (located in the temporal lobe).

  Next, the chapter examines criticisms of research into brain differences in people with schizophrenia which point to possible flaws in the studies involved. These include the low reliability of the construct of schizophrenia which may compromise research findings because the subjects involved in research can differ widely. Critics point out that large ventricles are not a specific cause of schizophrenia given that they appear in other conditions, like alcoholism. Also, dissenters argue that environmental factors like childhood trauma may contribute to the development of schizophrenia and may be associated with brain anomalies.

  The chapter examines some weaknesses of these dissenting views. Critics may overstate evidence to argue that antipsychotic medication causes brain anomalies. For example, they may cite studies that ‘suggest’ such an association but report them as ‘confirming’ this view. Also sometimes overstated is the possible role of childhood trauma. Critics may offer a mistrustful presentation of evidence concerning the role of drug companies, and the credibility of drug funded research findings and associated researchers. In presenting evidence in this way, critics may suggest that such researchers are driven by ideology rather than scientific rigor. A laudatory presentation of selected supportive evidence may be given by dissenters, for example aspects of an MRI study associating antipsychotic drugs and changes in brain volume.

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  Schizophrenia

  • Siegfried Kasper, George N. Papadimitriou(Authors)
  • 2009(Publication Date)
  • CRC Press

    (Publisher)

  This argues for considerable inhomogenity of brain abnormali-ties in schizophrenia. The major problem in looking for Brain Abnormalities in Schizophrenia is the con-siderable heterogeneity not only in the structural findings but also in the clinical symp-toms and course of the disease. This is not surprising, since the term “schizophrenia” remains until today an diagnostic construct that was defined decades ago by leading authorities in the field (Kraepelin, Schneider, Bleuler) and is now defined by commit-tees setting up operationalized criteria for the clinical diagnosis. Thus, it becomes more and more likely that schizophrenia comprises a quite inhomogeneous group of different neuropathologies and pathophysiologies resulting in similar clinical symptoms (com-parable, for example, to “dementia,” “fever,” or “rheumatism”). This might explain the enormous variance of all neurobiological finding in schizophrenic patients that is also characteristic for neuropathological studies, that are summarized in this chapter. Despite the enormous advances that have been achieved by the introduction of structural and functional imaging methods to clarify the neurobiology of schizophre-nia, only postmortem investigations applying modern microscopic, biochemical, and molecular biological techniques may help to clarify the cellular basis of schizophre-nia, and the cellular and molecular pathologic mechanisms behind these disturbances. During the past two decades, a plethora of studies has been published pointing not only to alterations in mean volumes, neuron and glial cell densities in different brain areas in schizophrenia, but also to characteristic changes in neurotransmitter/receptor sys-tems, growth factors, hormones, regulatory proteins, and brain energy metabolism. 87 9

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  Biological Psychiatry

  • Edward Bittar(Author)
  • 1999(Publication Date)
  • Elsevier Science

    (Publisher)

  Later maturational events alone might trigger these, building as they would on damaged foundations. Alternatively, environmental factors (e.g., stressors) could trigger the appearance of symptoms in at-risk individuals carrying a neurodevelopmental abnormality (Weinberger, 1987). The presence of a neurodevelopmental disturbance remains an hypothesis of considerable potency. Functional Indices of Brain Changes in Schizophrenia In parallel with studies that have examined the structure and chemistry of the schizophrenic brain, there have also been studies that have examined its activity. The electrical activity of the brain is known to be altered in schizophrenic patients. Abnormalities have been found in the auditory P300, an event-related potential generated by novel relevant stimuli, in schizophrenic patients (as it has in other groups of patients). More intriguingly, there appears to be some relationship between this and reduction in the volume of the left posterior superior temporal gyms (McCadey et al., 1993). However, most information over the last several The Biological Basis of Schizophrenia 247 years about the functional state of the brain has not come from electrophysiologi-cal studies but from positron emission tomography (PET) and other functional imaging techniques. The first studies to investigate regional cerebral blood flow (rCBF) in patients were undertaken in Sweden by David Ingvar and colleagues, who showed that there was abnormally low activity in the prefrontal cortex of many, but not all, schizophrenic patients (Ingvar and Franzen, 1974; see Ingvar, 1995, for review). The term hypofrontality was used to describe this phenome-non, which has since been observed in many laboratories around the world. What has become more obvious with time is that (1) not all patients show hypofrontality and (2) many other groups of patients also have the condition.

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  Introduction to Psychiatry

  Preclinical Foundations and Clinical Essentials

  • Audrey Walker, Steven Schlozman, Jonathan Alpert(Authors)
  • 2021(Publication Date)
  • Cambridge University Press

    (Publisher)

  This means that insults during brain development increase the morbid risk for the condition, but once an active disor- der is triggered, additional loss of functioning ensues. This hypothesis is supported by the finding that a longer DUP is associated with worse biological measures such as gray matter volume as well as with worse clinical outcomes. Note that neurode- generation in this context does not refer to neuropathologically defined changes, as in Alzheimer’s disease, but rather to progressive dysfunction in neural circuitry and grey matter volume loss. Some theories of biological abnormality in the brains of individuals with schiz- ophrenia focus on the dopamine system. This is because substances of abuse that enhance dopamine signaling are psychotomimetic, whereas drugs that block do- pamine neurotransmission are antipsychotic. The latter were discovered through serendipity, as there was no a priori reason to suspect dopaminergic dysfunction in schizophrenia. Although dopamine no doubt plays a role, it is only one of multiple neurochemical systems where abnormalities are found. Research has identified significant abnormalities in GABAergic interneurons in the cerebral cortex and limbic system of people with schizophrenia. This is significant because these neu- rons may function as inhibitory filters, allowing information signals to be trans- mitted while silencing inappropriate background activity. In addition, multiple lines of convergent evidence suggest that the ionotropic glutamate NMDA receptor is hypofunctioning in schizophrenia. This would lead to abnormalities in learning and memory, as well as moment to moment information processing in the human brain. Several small molecules (e.g., glycine and D-serine) that enhance NMDA receptor function have shown modest therapeutic effects in schizophrenia.

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  Functional MRI

  Applications in Clinical Neurology and Psychiatry

  • Mark D'Esposito(Author)
  • 2006(Publication Date)
  • CRC Press

    (Publisher)

  INTRODUCTION Schizophrenia is a common and devastating mental illness that affects approximately 1% of the population worldwide. Neuroimaging findings now form part of the bedrock of clinical investigation into this disorder. Following on the heels of structural imaging findings of increased ventricular spaces and reduced brain volumes, decreased dorso-lateral prefrontal cortex (DLPFC) activity or hypofrontality helped to establish schizophre-nia as biological in origin, to encourage a dialogue between basic and clinical scientists regarding neurochemistry, neuronal pathol-ogy, and molecular biology within DLPFC, and to foster a keener interest in cognitive dysfunction and its potential pharmacological remediation. However, as the methodology has matured, the essential questions regard-ing brain dysfunction in schizophrenia have changed as well. Some questions have been altered as a result of new neuroimaging findings. For example, decreased DLPFC activity is not the sole signature of dysfunction in schizophrenia. Some questions have been changed in scope. Instead of an exclusive focus on isolated regions of dysfunction, experiments and analyses are increasingly aimed at networks and interactions within them. Finally, some questions have been changed in kind as the result of rapid advances in other research disciplines. Elucidating the relationship between genetic variation and regional brain activation is a challenge that did not exist in the pre-genomic era. This chapter will address recent findings relevant to each of these issues, since new answers may ultimately drive the field in unexpected directions as further improve-ments in diagnosis and treatment are still desperately needed. OVERVIEW OF SCHIZOPHRENIA To put a wide range of neuroimaging research into some context, it is helpful to consider some basic observations about the illness.

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  Neuroimaging in Psychiatry

  • Cynthia H. Y. Fu, Carl Senior, Tamara Russell, Daniel R. Weinberger, Robin Murray, Cynthia H. Y. Fu, Carl Senior, Tamara Russell, Daniel R. Weinberger, Robin Murray(Authors)
  • 2003(Publication Date)
  • CRC Press

    (Publisher)

  Many difficulties attend the search for core structural and functional abnormalities in schizophrenia. These are rooted in an incomplete understanding of the illness itself and the extent to which it may be considered a unitary phenomenon. This uncertainty may account for a good deal of the inconsistency surrounding structural and functional imaging findings in schizophrenia. Furthermore, studies of brain function carry with them additional uncertainties surrounding the extent to which chosen ‘activation’ tasks may succeed in isolating and manipulating the cognitive processes of interest. These uncertainties are compounded when the same tasks are carried out by schizophrenic people since unequal performance levels introduce further ambiguity and even matched performance may be achievable through activation of different brain systems. Nevertheless, careful group selection, informed perhaps by more specific subgrouping on the basis of both phenotypic and genotypic features, is likely to have a major impact, particularly when combined with improved models of cognitive function. In this setting the techniques may realize an exciting potential. This potential, however, addresses only one aspect of structure–function relations in the brain: that of functional segregation. A functionally segregated view of the brain is based upon the notion that different functions and processes are carried out in different parts of the brain. As a partial description of brain organization, this is indisputable. It is not, however, complete. An understanding of brain function (and dysfunction) must also acknowledge the enormous degree of interregional connectivity and the compelling likelihood that separable regions, while showing functional specialization, must act as parts of integrated systems. This description of brain organization, i.e. in terms of functional integration, will be discussed in the final section with particular emphasis on its disruption as a key feature of schizophrenia. We will examine, furthermore, the peculiar advantages of the functional neuroimaging techniques to evaluating brain function in terms of interregional integration.

  Schizophrenia: a disorder of brain integration?

  Since brain function may be fully characterized only with reference both to regional specialization of function and to the integration of brain regions with differing functions, we must consider the possibility that the core disturbance in schizophrenia is a distributed one. Does schizophrenia exist as a disconnection syndrome?95

  Before considering the insights that may be offered by high-resolution, whole brain functional neuroimaging, it is important to clarify what is meant by the term disconnection in the current formulation. We are referring specifically to a functional disconnection. The existence of such a disconnection does not necessarily depend upon a gross disturbance of white matter tracts (i.e. an anatomical disconnection). That is not to say that there is no infrastructural marker for the functional disconnection (e.g. at the synaptic level) but we wish to confine our discussion to a disconnection expressed in terms of abnormal functional interactions between brain regions. We suggest that such deficits may be invoked to explain the symptoms of schizophrenia more adequately than the idea of schizophrenia as a localized brain impairment.

  Before considering the contribution of functional neuroimaging (specifically that of fMRI) to this theoretical position, it is worth identifying some of the key pieces of evidence that point towards schizophrenia as a disconnection syndrome. One important observation was the degree of symptomatic overlap between schizophrenia and metachromatic leukodystrophy, a condition accompanied by disruptions in white matter tracts (i.e. anatomical disconnectivity), and features of psychosis that, to some extent, mimic acute schizophrenia.96 While this is not to suggest that identical deficits underlie the two conditions, the anatomical disconnection as a partial model of schizophrenia may be informative. Furthermore, chemical disconnection produced by the acute administration of phencyclidine (a NMDA [N-methyl-D-aspartate] receptor antagonist) also produces symptoms that compellingly mimic schizophrenia.97 This re-emerging viewpoint of schizophrenia as a disconnection disorder is lent support by consideration of the condition within the field of connectionist modelling

  98 ,99

  and by suggestionsthat a core (but distributed) deficit in schizophrenia lies in an abnormal neuronal plasticity.100

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  The Boundaries of Consciousness: Neurobiology and Neuropathology

  • Steven Laureys(Author)
  • 2006(Publication Date)
  • Elsevier Science

    (Publisher)

  Chapter 22 Functional brain imaging of symptoms and cognition in schizophrenia

  Tilo T.J. Kircher* [email protected] , Renate Thienel

  Department of Psychiatry and Psychotherapy, University of Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany * Corresponding author. Tel.: +49 (0)241 8089637; Fax: +49 (0)241 8082401

  Abstract

  The advent of functional magnetic resonance imaging and positron emission tomography has provided novel insights into the neural correlates of cognitive function and psychopathological symptoms. In patients with mental disorders, cognitive and emotional processes are disrupted. In this chapter, we review the basic methodological and conceptual principles for neuroimaging studies in these patients. By taking schizophrenia as an example, we outline the cerebral processes involved in the symptoms of this disorder, such as auditory hallucinations and formal thought disorder. We also characterize the neural networks involved in their emotional and cognitive dysfunction.

  Introduction

  Mental phenomena and their disruption, evident in mental disorders, result from disturbances in the interaction of different neural networks. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) enable us to visualize cerebral function. We use schizophrenia as an example of how core psychopathological symptoms of the disorder, such as auditory hallucinations and formal thought disorder (FTD) as well as cognitive deficits, can be represented by their cerebral correlates. Since there are many myths and misconceptions about schizophrenia, we will concentrate in this chapter on established facts on brain–behavior relationships in this disorder. We will further discuss briefly on models and recent data on consciousness and self-consciousness in schizophrenia (Kircher and David, 2003 ; Kircher and Leube, 2003

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  Developmental Psychopathology, Developmental Neuroscience

  • Dante Cicchetti(Author)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  Figure 23.1 ). As noted previously, the most well established disease-related deficits in schizophrenia involve frontal and temporal lobe structures, abnormalities of which have been linked to the occurrence of hypoxia-associated birth complications among individuals with schizophrenia. Nevertheless, as we shall see, additional progressive deficits in these brain structures appear to characterize the period proximal to illness onset. While there is debate regarding the interpretation of longitudinal MRI studies, as the reported rates of annualized gray matter decline seem unsustainably high (Weinberger & McClure, 2002), emerging evidence suggests that rates of decline in gray matter may level off with age, distinct from the course of atrophy typically associated with neurodegenerative disorders (Mathalon, Rapoport, Davis, & Krystal, 2003). The question then becomes, if these disease–related deficits are present to some degree from early in life, what mechanisms cause them to further deteriorate in adolescence/early adulthood, and are these mechanisms primary or secondary to the emergence of psychosis?

  Clinical High-Risk Studies and Early Detection

  With the shift in focus from an early neurodevelopmental model of schizophrenia to increasing interest in more proximal developmental risk factors, a new research strategy has emerged and gathered considerable support. Building on traditional high-risk approaches, the so-called clinical high-risk (CHR) paradigm (Yung & McGorry, 1996; Yung et al., 1998) goes beyond indicators of genetic vulnerability to focus on clinical features that are believed to reflect heightened vulnerability for imminent onset of psychosis. A central goal in CHR research is to prospectively follow a well-characterized group of putatively prodromal individuals through the period of conversion to gain a deeper understanding of the progression of clinical, biological, and neurocognitive changes that characterize the onset of overt illness. Such studies may enhance our understanding of the pathophysiology of psychotic illness, and allow for the discrimination of the schizophrenia prodrome

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  Handbook of Medical Psychiatry

  • Jair C. Soares, Samuel Gershon, Jair C. Soares, Samuel Gershon(Authors)
  • 2003(Publication Date)
  • CRC Press

    (Publisher)

  16 Neuroimaging Findings in Schizophrenia From Mental to Neuronal Fragmentation LAWRENCE S. KEGELES and MARC LARUELLE Columbia University, New York, New York, U.S.A. I. INTRODUCTION Over the last 20 years, the ability to image the living human brain underwent enormous developments, opening direct windows into brain function and cellu-lar processes associated with health and disease. Brain imaging techniques are classically divided into struc-tural, functional, and chemical imaging, although the distinctions among these domains are somewhat arbitrary. These techniques are based either on the injection of radioactive moieties whose distribution is recorded with positron emission tomography (PET) or single photon emission computerized tomography (SPECT), or on the direct detection of molecules based on their intrinsic magnetic properties with mag-netic resonance imaging (MRI and fMRI) or spectro-scopy (MRS). This chapter will summarize important results obtained using brain imaging techniques in schizophre-nia research, and the various insights on the pathophy-siology and treatment of schizophrenia gained by these results. A more detailed technical discussion of these various imaging modalities is found in Chapter 7 of this volume. II. STRUCTURAL IMAGING Tomographic imaging, beginning with CT scanning and shortly thereafter MRI, has enabled rapid progress in studying brain structure in vivo. Following the initial CT report of enlarged ventricles in schizo-phrenia [1], a large number of CT studies replicated this observation [reviewed in 2–4]. This finding is the most replicated and well-established brain imaging finding in schizophrenia, and was historically impor-tant in establishing that schizophrenia is a brain dis-ease.

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  Schizo-Obsessive Disorder

  • Michael Poyurovsky(Author)
  • 2013(Publication Date)
  • Cambridge University Press

    (Publisher)

  Reprinted with permission from the Journal of Neuropsychiatry and Clinical Neurosciences (copyright 2007, American Psychiatric Association). 184 Chapter 10: Neurobiology of schizo-obsessive disorder research methodology also failed to find any significant group differences (Sevincok et al., 2006; Thomas and Tharyan, 2011; Tumkaya et al., 2012). Hence, it is conceivable that a pervasive schizophrenia-related “soft neurological deficit” superimposes any additional deficits related to a comorbid disorder, such as OCD. Neurophysiological alterations Neurophysiological evaluation involves assessment of brain electrical activity using scalp electrodes at rest or during participation in experimental paradigms. The major advantage of these techniques is the high temporal resolution that enables tracking the various stages of information processing from primary sensory to association brain regions (Javitt et al., 2008). Neurophysiological approaches include among others (Braff and Light, 2005; Keshavan et al., 2008):  P300 event-related potentials (ERP), which involve averaging EEG epochs time-locked to repeated presentations of specific stimuli (typically auditory or visual) with the positive wave occurring about 300 ms after the delivery of a task-relevant stimulus considered to reflect higher cognitive functions; schizophrenia is associated with blunted amplitude of the auditory P300 response to salient stimuli.  P50 auditory-evoked response, the ability of the brain to attenuate the P50 response (a positive ERP component about 50 ms after each click) to the second stimulus when presented with two clicks separated by 500 ms; this inhibitory effect is reduced in schizophrenia.

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  Psychopathology

  The Evolving Science of Mental Disorder

  • Steven Matthysse, Francine M. Benes, Deborah L. Levy, Jerome Kagan(Authors)
  • 1996(Publication Date)
  • Cambridge University Press

    (Publisher)

  These factors have been particularly important to schizophrenia, where brain abnormalities are often more subtle and therefore harder to detect, than for other pathophysiological diseases, and where, consequently, precise and accurate measurements become that much more important. Our lab- oratory has applied these newly developed MR imaging techniques to high spatial resolution MR images in order to quantify in vivo differ- ences between the brains of normal controls and patients afflicted with schizophrenia. These data will be presented, following a review of MR temporal lobe studies in schizophrenia, in order to provide an example of what new image-processing techniques offer future stud- ies in this field. Review of temporal lobe MR imaging studies in schizophrenia Table 4.2 summarizes 24 MRI studies of temporal lobe structures in schizophrenia, including asymmetry findings in the size of the lateral ventricles. We first comment on the studies measuring temporal lobe Temporal lobe abnormalities in schizophrenia 77 volume, where differences in measurement technique, as well as in subject populations, may account for differing findings. Three studies have reported no differences in temporal lobe size between normals and schizophrenics (Barta et al., 1990; Shenton et al., 1992; Swayze et al., 1992), five studies have reported left temporal lobe reduction in schizophrenia (Coffman et al., 1989; Johnstone et al., 1989; Rossi et al., 1989, 1990; DeLisi et al., 1991), one study has reported gray matter reduction in the left temporal lobe (Suddath et al., 1990), three studies have reported bilateral reduction in the temporal lobe (Suddath et al., 1989; Dauphinais et al., 1990; Rossi et al., 1991 - compared to bipolars), and one study has reported right temporal lobe reduction in schizophrenia (Bogerts et al., 1990 - male first episode patients).

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