Postmortem studies in schizophrenia

Abstract

For over a century, postmortem studies have played a central part in the search for the structural and biochemical pathology of schizophrenia. However, for most of this time, little progress has been made. Recently, the situation has begun to change, helped by the emergence of more powerful methodologies and research designs, and by the availability of brain imaging to provide complementary information. As a result, it can now be clearly concluded that there are structural cerebral abnormalities in schizophrenia that are intrinsic to the disorder. The neuropathological process is not primarily degenerative, but involves a change in the normal cytoarchitecture of the brain, probably originating in development. Neurochemically, there is postmortem evidence for alterations in several transmitter systems including dopamine, glutamate, serotonin, and γ-aminobutyric acid (GABA). The cardinal findings are reviewed here, together with a consideration of the conceptual and methodological issues that face postmortem studies of schizophrenia.

Gene-sex interactions in schizophrenia: focus on dopamine neurotransmission

“…The bulk of the evidence suggests that the DAergic deficits in schizophrenia are underpinned by functional, rather than constitutive, abnormalities. Indeed, the majority of studies on post-mortem tissues have failed to identify consistent alterations in the expression of DAergic targets (Harrison, 2000 ). Accordingly, multiple large-scale genetic analyses have found no robust association for DAergic genes and schizophrenia (Hoogendoorn et al, 2005 ; Alvarez et al, 2010 ), and instead point to a predominant involvement of glutamatergic targets (Collier and Li, 2003 ).…”

Modeling psychiatric disorders: from genomic findings to cellular phenotypes

“… 87 Computed tomography and magnetic resonance imaging analyses have revealed structural changes in the brain of SCZ patients, such as enlarged lateral and third ventricles, smaller cortical volumes, smaller gray matter volumes and larger basal ganglia (reviewed by ref. 88 ). Morphometric changes generally do not progress overtime and therefore may match histological findings in postmortem tissue, which include altered cortical and hippocampal pyramidal neuron size, decreased interneuron numbers and reduced dendritic spine densities.…”

“…Morphometric changes generally do not progress overtime and therefore may match histological findings in postmortem tissue, which include altered cortical and hippocampal pyramidal neuron size, decreased interneuron numbers and reduced dendritic spine densities. 88 , 89 …”

The biology of schizophrenia

“…this synapse in response to PCP We interpreted these data to mean that a psychotomimetic compound like PCP can decrease glutamatergic transmission in hippocampus, thus critically interfering with hippocampal function. Since the hippocampus is a brain region already known from postmortem studies in schizophrenia to be abnormal, 85 these conclusions seemed plausible. Our own postmortem findings, most importantly including a decrease in NR] expression in the schizophrenic hippocampus, 86 are consistent with this current, formulation.…”

“…These include postmortem tissue studies and animal, model experiments. Findings from postmortem brain studies in schizophrenia are reviewed in this issue by Harrison et al 85 From the substantial body of postmortem work reviewed, several guiding formulations emerge: (i) the limbic system has been consistently identified as affected in schizophrenia; and (ii) although the examination of postmortem transmitter systems has been skewed toward the monoamines and dopamine in particular, it. is clear that many chemical systems are affected in schizophrenia.…”