Positron emission tomography and subcortical glucose metabolism in schizophrenia
ABSTRACT Our previous observation of a disturbed subcortical-to-cortical gradient of activity in schizophrenia was further elucidated by examining glucose metabolism in three subcortical structures: lenticular nucleus, caudate nucleus, and thalamus. Local cerebral glucose metabolism was determined with 18F- fluorodeoxyglucose using positron emission tomography (PET) in a sample of 20 unmedicated schizphrenics and 18 normal volunteers. Repeated evaluations were performed for 12 schizophrenics following treatment with psychotropic medications and for 11 controls. Unmedicated schizophrenics had lower cortical and caudate absolute metabolic rates. Subcortical-to-cortical ratios for the lenticular nucleus and thalamus were increased in schizophrenics compared with controls, reflecting a preservation of activity in these structures relative to decreased cortical metabolism. When patients were grouped by length of medication-free period before the initial study, there was a trend for patients who had been medication free < 6 months to have higher subcortical ratios. However, there were no consistent effects of medication in the subsample of patients whose PET studies were repeated following treatment. The results demonstrate relative hypermetabolism in structures implicated in dopamine pathways. An understanding of the physiological significance of this finding awaits the combined measurement of metabolic activity and neuroreceptors in schizophrenics.
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ABSTRACT: Postmortem and in vivo imaging studies have revealed structural and functional pathology in the thalamus in schizophrenia. We have reported a series neurochemical changes in the thalamus in schizophrenia, including decreased expression of NMDA receptor subunit transcripts and increased levels of NMDA receptor-associated intracellular proteins like postsynaptic density protein 95 (PSD95) and neurofilament-light (NF-L) chain that link the NMDA receptor to downstream signal transduction pathways. NF-L, along with the neurofilament subunit proteins NF-medium (NF-M) chain and NF-heavy (NF-H) chain, assemble to form neurofilaments, one of the most abundant cytoskeletal elements. While the neurofilament subunits play a crucial role in sustaining the neuronal cytoskeleton, two subunits, NF-L and NF-M, also participate in neurotransmission, interacting with the NMDA and the dopamine Dl receptors, respectively. In the present study, using in situ hybridization, we determined whether all of the neurofilament subunits (NF-L, NF-M, and NF-H) are abnormally expressed in the thalamus in schizophrenia, or whether the abnormality is specific to NF-L. We found that NF-L and NF-M transcripts are both increased in schizophrenia, but the expression of NF-H is unchanged. Both NF-L and NF-M play an important role in maintaining the neuronal cytoskeleton, so abnormal transcript expression may be associated with structural thalamic pathology. Alternatively, since these proteins are also known to interact with the NMDA and Dl dopamine receptors, abnormal transcript levels may be associated with abnormalities of neurotransmission in the thalamus in schizophrenia.Thalamus & Related Systems 06/2004; 2(04):265 - 272.
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ABSTRACT: A quantitative cortical model is developed, based on both computational and simulation approaches, which relates measured changes in cortical activity of gray matter with changes in the integrity of longitudinal fiber pathways. The model consists of modules of up to 5,000 neurons each, 80% excitatory and 20% inhibitory, with these having different degrees of synaptic connectiveness both within a module as well as between modules. It is shown that if the inter-modular synaptic connections are reduced to zero while maintaining the intra-modular synaptic connections constant, then activity in the modules is reduced by about 50%. This agrees with experimental observations in which cortical electrical activity in a region of interest, measured using the rate of oxidative glucose metabolism (CMRglc(ox)), is reduced by about 50% when the cortical region is isolated, either by surgical means or by transient cold block. There is also a 50% decrease in measured cortical activity following inactivation of the nucleus of Meynert and the intra-laminar nuclei of the thalamus, which arise either following appropriate lesions or in sleep. This occurs in the model if the inter-modular synaptic connections require input from these nuclei in order to function. In schizophrenia there is a 24% decrease in functional anisotropy of longitudinal fasciculi accompanied by a 7% decrease in cortical activity (CMRglc(ox)).The cortical model predicts this, namely for a 24% decrease in the functioning of the inter-modular connections, either through the complete loss of 24% of axons subserving the connections or due to such a decrease in the efficacy of all the inter-modular connections, there will be about a 7% decrease in the activity of the modules. This work suggests that deterioration of longitudinal fasciculi in schizophrenia explains the loss of activity in the gray matter.PLoS ONE 04/2013; 8(4):e60518. · 3.53 Impact Factor
- Fortschritte der Neurologie · Psychiatrie 10/2004; 72(11):621-634. · 0.76 Impact Factor