Volume and neuron number of the lateral geniculate nucleus in schizophrenia and mood disorders

Dorph‐Petersen, Karl‐Anton; Carić, Damira; Saghafi, Ramin; Zhang, Wei; Sampson, Allan R.; Lewis, David A.

doi:10.1007/s00401-008-0410-2

Cited by 69 publications

(58 citation statements)

References 78 publications

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“…Finally, the effects of a lifetime of severe mental illness, and the stress associated with it, may not be disease-specific. Inclusion of a comparison group with a different mental illness permits assessment of the specificity of the findings to a particular disorder (Dorph-Petersen et al, 2009;McCullumsmith and Meador-Woodruff, 2002). In summary, postmortem studies are reliant on descriptive criteria for diagnostic assessment for diseases that are typically quite heterogeneous in their clinical presentation.…”

Section: Diagnosis and Phenotypementioning

confidence: 99%

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

McCullumsmith

Hammond

Shan

et al. 2013

Neuropsychopharmacol

107

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We propose that postmortem tissue is an underutilized substrate that may be used to translate genetic and/or preclinical studies, particularly for neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from subjects with schizophrenia have been extensively studied, and thus serve as a useful vehicle for illustrating the challenges associated with this biological substrate. Schizophrenia is likely caused by a combination of genetic risk and environmental factors that combine to create a disease phenotype that is typically not apparent until late adolescence. The complexity of this illness creates challenges for hypothesis testing aimed at understanding the pathophysiology of the illness, as postmortem brain tissues collected from individuals with schizophrenia reflect neuroplastic changes from a lifetime of severe mental illness, as well as treatment with antipsychotic medications. While there are significant challenges with studying postmortem brain, such as the postmortem interval, it confers a translational element that is difficult to recapitulate in animal models. On the other hand, data derived from animal models typically provide specific mechanistic and behavioral measures that cannot be generated using human subjects. Convergence of these two approaches has led to important insights for understanding molecular deficits and their causes in this illness. In this review, we discuss the problem of schizophrenia, review the common challenges related to postmortem studies, discuss the application of biochemical approaches to this substrate, and present examples of postmortem schizophrenia studies that illustrate the role of the postmortem approach for generating important new leads for understanding the pathophysiology of severe mental illness.

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Section: Diagnosis and Phenotypementioning

confidence: 99%

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

McCullumsmith

Hammond

Shan

et al. 2013

Neuropsychopharmacol

107

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“…This seems especially true in schizophrenia. As determined by magnetic resonance imaging and postmortem anatomy in schizophrenic patients, of those thalamic areas studied, first order nuclei appear relatively normal but higher order nuclei (e.g., the medial dorsal nucleus and pulvinar) are shrunken with neuronal loss and reduced activity (14,28,32,34,39,70,108,109,117). This suggests that schizophrenia may specifically disrupt transthalamic circuits, which could account for many of the cognitive issues associated with schizophrenia, since such disruption would impair corticocortical communication.…”

Section: Relationship To Schizophreniamentioning

confidence: 95%

Functioning of Circuits Connecting Thalamus and Cortex

Sherman¹

2017

Comprehensive Physiology

131

108

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Glutamatergic pathways in thalamus and cortex are divided into two distinct classes: driver, which carries the main information between cells, and modulator, which modifies how driver inputs function. Identifying driver inputs helps to reveal functional computational circuits, and one set of such circuits identified by this approach are cortico-thalamo-cortical (or transthalamic corticocortical) circuits. This, in turn, leads to the conclusion that there are two types of thalamic relay: first order nuclei (such as the lateral geniculate nucleus) that relay driver input from a subcortical source (i.e., retina), and higher order nuclei (such as the pulvinar) which are involved in these transthalamic pathways by relaying driver input from layer 5 of one cortical area to another. This thalamic division is also seen in other sensory pathways and beyond these so that most of thalamus by volume consists of higher-order relays. Many, and perhaps all, direct driver connections between cortical areas are paralleled by an indirect cortico-thalamo-cortical (transthalamic) driver route involving higher order thalamic relays. Such thalamic relays represent a heretofore unappreciated role in cortical functioning, and this assessment challenges and extends conventional views regarding both the role of thalamus and mechanisms of corticocortical communication. Finally, many and perhaps the vast majority of driver inputs relayed through thalamus arrive via branching axons, with extrathalamic targets often being subcortical motor centers. This raises the possibility that inputs relayed by thalamus to cortex also serve as efference copies, and this may represent an important feature of information relayed up the cortical hierarchy via transthalamic circuits. © 2017 American Physiological Society. Compr Physiol 7:713-739, 2017.

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“…Likewise, two studies by two different groups of authors (Selemon and Begovic, 2007; Dorph-Petersen et al, 2009) of the subregions of the lateral geniculate nucleus (LGN) did not reveal any changes in volume, neuron or glial cell numbers associated with schizophrenia.…”

Section: Postmortem Thalamic Findings In Schizophrenia Based Upon mentioning

confidence: 96%

Postmortem structural studies of the thalamus in schizophrenia

Dorph‐Petersen

Lewis

2017

Schizophrenia Research

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In this review, we seek to answer the following question: Do findings in the current literature support the idea that thalamo-cortical dysfunction in schizophrenia is due to structural abnormalities in the thalamus? We base our review on the existing literature of design-unbiased stereological studies of the postmortem thalamus from subjects with schizophrenia. Thus, all reported results are based upon the use of unbiased principles of sampling to determine volume and/or total cell numbers of thalamus or its constituent nuclei. We found 28 such papers covering 26 studies. In a series of tables we list all positive and negative findings from the total thalamus, the mediodorsal, pulvinar and anterior nuclei, as well as less frequently studied thalamic regions. Only four studies examined the entire thalamus and the results were inconsistent. We found largely consistent evidence for structural changes (reduced volume and cell numbers) in the pulvinar located in the posterior thalamus. In contrast, findings in the mediodorsal thalamic nucleus are inconsistent, with the largest and most recent studies generally failing to support earlier reports of a lower number of neurons in schizophrenia. Thus, the current findings of stereological studies of the thalamus in schizophrenia support the idea that thalamo-cortical dysfunction in schizophrenia might be attributable, at least in part, to structural alterations in the pulvinar that could impair thalamic inputs to higher order cortical association areas in the frontal and parietal lobes. However, more studies are needed before robust conclusions can be drawn.

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Volume and neuron number of the lateral geniculate nucleus in schizophrenia and mood disorders

Cited by 69 publications

References 78 publications

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

Functioning of Circuits Connecting Thalamus and Cortex

Postmortem structural studies of the thalamus in schizophrenia

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