Maldistribution of Interstitial Neurons in Prefrontal White Matter of the Brains of Schizophrenic Patients

Akbarian, Schahram; Jj, Kim; Potkin, Steven G.; Wp, Hetrick; We, Bunney; Eg, Jones

doi:10.1001/archpsyc.1996.01830050061010

Cited by 367 publications

(239 citation statements)

References 85 publications

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“…Altered neuronal densities were reported in the prefrontal cortex (Akbarian et al, 1996;Anderson et al, 1996;Connor et al, 2009;Daviss and Lewis, 1995;Ikeda et al, 2004;Joshi et al, 2012;Morris et al, 2008;Rajkowska et al, 1998;Selemon et al, 1995Selemon et al, , 1998Selemon et al, , 2003Yang et al, 2011), auditory cortex (Dorph-Petersen et al, 2009), cingulate cortex (Benes, 1991(Benes, , 1993Brune et al, 2010;Connor et al, 2009), entorhinal cortex (Arnold et al, 1991;Falkai et al, 2000;Jakob and Beckmann, 1986;Kovalenko et al, 2003;Wang et al, 2011), fusiform cortex (Di Rosa et al, 2009), occipital cortex (Selemon et al, 1995), parietal cortex (Chance et al, 2005), visual cortex (Dorph-Petersen et al, 2007), thalamus (Young et al, 2000), hypothalamus (Bernstein et al, 1998), striatum (Kreczmanski et al, 2007), amygdala (Kreczmanski et al, 2007), and hippocampus (Konradi et al, 2011) in post-mortem brain tissue from schizophrenic patients. Interestingly, many of these reports show specific defects in GABAergic interneuron density or distribution (Benes et al, 1991;Chance et al, 2005;Daviss and Lewis, 1995;Di Rosa et al, 2009;Ikeda et al, 2004;Joshi et al, 2012;Konradi et al, 2011;Morris et al, 2008;Wang et al, 2011;Yang et al, 2011).…”

Section: Anatomical and Histological Findings Suggest Neurodevelopmenmentioning

confidence: 99%

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Schmidt

Mirnics

2014

Neuropsychopharmacol

180

130

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The origins of schizophrenia have eluded clinicians and researchers since Kraepelin and Bleuler began documenting their findings. However, large clinical research efforts in recent decades have identified numerous genetic and environmental risk factors for schizophrenia. The combined data strongly support the neurodevelopmental hypothesis of schizophrenia and underscore the importance of the common converging effects of diverse insults. In this review, we discuss the evidence that genetic and environmental risk factors that predispose to schizophrenia disrupt the development and normal functioning of the GABAergic system.

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Section: Anatomical and Histological Findings Suggest Neurodevelopmenmentioning

confidence: 99%

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Schmidt

Mirnics

2014

Neuropsychopharmacol

180

130

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“…(ii) Selective displacement of interstitial white matter neurons in the frontal lobes of schizophrenics that may reflect an alteration in the migration of subplate neurons or in the pattern of programmed cell death. Both could be associated with abnormal neural circuitry and connectivity (Akbarian et al, 1996). Electron microscopy of synaptic ultrastructure in regions associated with the dopaminergic system has revealed changes that are consistent with anomalous plasticity: namely, anomalous axonal sprouting with an increase in axospinous, and decrease in axodendritic, synapses in schizophrenia (Uranova, 1996).…”

Section: Theoretical Neurobiologymentioning

confidence: 99%

The disconnection hypothesis

Friston

1998

Schizophrenia Research

782

469

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This article reviews the disconnection hypothesis of schizophrenia and presents a mechanistic account of how dysfunctional integration among neuronal systems might arise. This neurobiological account is based on the central role played by neuronal plasticity in shaping the connections and the ensuing dynamics that underlie brain function. The particular hypothesis put forward here is that the pathophysiology of schizophrenia is expressed at the level of modulation of associative changes in synaptic efficacy; specifically the modulation of plasticity in those brain systems responsible for emotional learning and memory, in the post-natal period. This modulation is mediated by ascending neurotransmitter systems that: (i) have been implicated in schizophrenia; and (ii) are known to be involved in consolidating synaptic connections during learning. The proposed pathophysiology would translate, in functional terms, into a disruption of the reinforcement of adaptive behaviour that is consistent with the disintegrative aspects of schizophrenic neuropsychology.

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“…Importantly, if glial dysfunction is confirmed in schizophrenia, this alone could explain abnormal neuronal cytoarchitecture and functional deficits including functional fronto-temporal disconnections observed in schizophrenia (see also the recent review of white matter in schizophrenia by Davis et al (2003). Finally, Akbarian et al (1996) reported a maldistribution of the interstitial neurons in both prefrontal and temporal white matter in schizophrenia brains. The observed altered neuronal distributions in both prefrontal and temporal lobe regions suggested to these investigators that neurodevelopmental abnormalities were present in at least a subgroup of patients, and that such abnormalities could alter the connectivity of these brain regions.…”

Section: Introductionmentioning

confidence: 99%

A review of diffusion tensor imaging studies in schizophrenia

Kubicki

McCarley

Westin

et al. 2007

Journal of Psychiatric Research

684

532

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Both post-mortem and neuroimaging studies have contributed significantly to what we know about the brain and schizophrenia. MRI studies of volumetric reduction in several brain regions in schizophrenia have confirmed early speculations that the brain is disordered in schizophrenia. There is also a growing body of evidence suggesting that a disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, are responsible for the clinical symptoms and cognitive dysfunctions observed in this disorder. Thus an interest in white matter fiber tracts, subserving anatomical connections between distant, as well as proximal, brain regions, is emerging. This interest coincides with the recent advent of diffusion tensor imaging (DTI), which makes it possible to evaluate the organization and coherence of white matter fiber tracts. This is an important advance as conventional MRI techniques are insensitive to fiber tract direction and organization, and have not consistently demonstrated white matter abnormalities. DTI may, therefore, provide important new information about neural circuitry, and it is increasingly being used in neuroimaging studies of psychopathological disorders. Of note, in the past five years 18 DTI studies in schizophrenia have been published, most describing white matter abnormalities. Questions still remain, however, regarding what we are measuring that is abnormal in this disease, and how measures obtained using one method correspond to those obtained using other methods? Below we review the basic principles involved in MR-DTI, followed by a review of the different methods used to evaluate diffusion. Finally, we review MR-DTI findings in schizophrenia.

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Maldistribution of Interstitial Neurons in Prefrontal White Matter of the Brains of Schizophrenic Patients

Cited by 367 publications

References 85 publications

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

The disconnection hypothesis

A review of diffusion tensor imaging studies in schizophrenia

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