Biomedical subjects

James H Meador-Woodruff

Publications and source records attributed to James H Meador-Woodruff.

At least 19 recordsLinked to original sources

PubMed2007

Expression of transcripts for myelination-related genes in the anterior cingulate cortex in schizophrenia.

Several recent studies have found changes in the expression of genes functionally related to myelination and oligodendrocyte homeostasis in schizophrenia. These studies utilized microarrays and quantitative PCR (QPCR), methodologies which do not permit direct, unamplified examination of mRNA expression. In addition, these studies generally only examined transcript expression in homogenates of gray matter. In the present study, we examined the expression of myelination-related genes previously implicated in schizophrenia by microarray or QPCR. Using in situ hybridization, we measured transcript expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), myelin-associated glycoprotein (MAG), transferrin (TF), quaking (QKI), gelsolin, myelin oligodendrocyte glycoprotein, v-erb-b2 erythroblastic leukemia viral oncogene homolog 3, erbb2 interacting protein, motility-related protein-1, SRY-box containing gene 10, oligodendrocyte transcription factor 2, peripheral myelin protein 22, and claudin-11 in both gray and white matter of the anterior cingulate cortex (ACC) in subjects with schizophrenia (n=41) and a comparison group (n=34). We found decreased expression of MAG, QKI, TF, and CNP transcripts in white matter. We did not find any differences in expression of these transcripts between medicated (n=31) and unmedicated (n=10) schizophrenics, suggesting that these changes are not secondary to treatment with antipsychotics. Finally, we found significant positive correlations between QKI and MAG or CNP mRNA expression, suggesting that the transcription factor QKI regulates MAG and CNP expression. Our results support the hypothesis that myelination and oligodendrocyte function are impaired in schizophrenia.

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PubMed2006

Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia.

Ampakines, positive AMPA receptor modulators, can improve cognitive function in schizophrenia, and enhancement of AMPA receptor-mediated currents by them potentiates the activity of antipsychotics. In vitro studies have revealed that trafficking of AMPA receptors is mediated by specific interactions of a complex network of proteins that also target and anchor them at the postsynaptic density (PSD). The aim of this study was to determine whether there are abnormalities of the molecules associated with trafficking and localization of AMPA receptors at the PSD in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. We analyzed AMPA receptor expression in DLPFC in schizophrenia, major depression, bipolar disorder, and a control group, by examining transcript levels of all four AMPA receptor subunits by in situ hybridization. We found decreased GluR2 subunit expression in all three illnesses, decreased GluR3 in major depression, and decreased GluR4 in schizophrenia. However, autoradiography experiments showed no changes in AMPA receptor binding; thus, we hypothesized that these changes in receptor subunit stoichiometry do not alter binding to the assembled receptor, but rather intracellular processing. In situ hybridization for AMPA-trafficking molecules showed decreased expression of PICK1 and increased expression of stargazin in DLPFC in schizophrenia, both restricted to large cells of cortical layer III. These data suggest that AMPA-mediated glutamatergic neurotransmission is compromised in schizophrenia, particularly at the level of AMPA-related PSD proteins that mediate AMPA receptor trafficking, synaptic surface expression, and intracellular signaling.

Adult↗

PubMed2006

Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder.

OBJECTIVES: Schizophrenia is associated with dysfunction of glutamatergic neurotransmission, and several studies have suggested glutamatergic abnormalities in bipolar disorder. Recent data suggest involvement of the NMDA receptor signaling complex, which includes NMDA receptor subunits as well as associated intracellular interacting proteins critical for NMDA receptor assembly, trafficking, and activation; the most well-characterized being PSD93, PSD95, SAP102, and NF-L. Previously, studies from our laboratories have described changes in glutamate receptor subunit transcript and binding site expression in schizophrenia and changes in NMDA receptor binding site expression in bipolar disorder in postmortem brain tissue. In the present work, we focus on the expression of these molecules in hippocampus in schizophrenia and bipolar affective disorder I. METHODS: We performed in situ hybridization to assess hippocampal expression of the transcripts encoding NMDA receptor subunits NR1, 2A, 2B, 2C and 2D, and the transcripts for the NMDA receptor associated PSD proteins PSD95, PSD93, NF-L, and SAP102 in subjects with schizophrenia, bipolar affective disorder I, and a comparison group. We also measured [(3)H]CGP39653 and [(3)H]MK-801 binding site expression in the hippocampus in schizophrenia. RESULTS: There was a significant decrease in the expression of transcripts for NR1 and NR2A subunits and SAP102 in bipolar disorder. We did not detect any changes in these transcripts or in binding site expression in the hippocampus in schizophrenia. CONCLUSIONS: We propose that the NMDA receptor signaling complex, including the intracellular machinery that is coupled to the NMDA receptor subunits, is abnormal in the hippocampus in bipolar disorder. These data suggest that bipolar disorder might be associated with abnormalities of glutamate-linked intracellular signaling and trafficking processes.

Binding Sites↗

PubMed2006

NMDA receptors and schizophrenia.

The pathophysiology of schizophrenia is poorly understood but is likely to involve alterations in excitatory glutamatergic signaling molecules in several areas of the brain. Clinical and experimental evidence has shown that expression of the N-methyl-D-aspartate (NMDA) receptor and intracellular NMDA receptor-interacting proteins of the glutaminergic synapse appear to be dysregulated in schizophrenia. It has been suggested that schizophrenia involves molecular changes in the glutamatergic pathways that mediate excitatory communication between multiple brain regions. Recent data also implicate abnormalities in cellular functions such as receptor trafficking and synaptic targeting.

Animals↗

PubMed2006

Dopamine receptor signaling molecules are altered in elderly schizophrenic cortex.

Alterations of molecules that mediate dopaminergic signal transduction have been found in schizophrenia, supporting the hypothesis of altered dopaminergic neurotransmission in this illness. To further explore this hypothesis, the authors measured transcript expression of three proteins involved in dopamine (DA) signaling in postmortem dorsolateral prefrontal and anterior cingulate cortex of elderly schizophrenic subjects and a comparison group. The transcript encoding calcyon, a protein that potentiates crosstalk between D1 DA receptors and Gq/11-linked receptors, was increased in schizophrenic prefrontal and cingulate cortex by 25%. Transcript levels of spinophilin, a protein enriched in dendritic spines that modulates excitatory neurotransmission, were increased 22% in dorsolateral prefrontal cortex but were unchanged in anterior cingulate cortex in schizophrenia. Levels of DARPP-32 mRNA, a downstream effector of dopaminergic neurotransmission, were similar in both groups for both cortical groups. These alterations in spinophilin and calcyon mRNA levels in schizophrenic prefrontal and cingulate cortex provide further evidence of altered dopaminergic neurotransmission in this illness.

Aged↗

PubMed2006

Serine racemase protein expression in cortex and hippocampus in schizophrenia.

Evidence of glutamatergic dysfunction in schizophrenia associated with the N-methyl-D-aspartate receptor has historically demonstrated changes primarily attributable to neurons. We propose an astrocytic component to N-methyl-D-aspartate receptor dysfunction in this illness. We studied the expression of serine racemase, an astrocytic enzyme which synthesizes the N-methyl-D-aspartate receptor coagonist D-serine, using Western blot analysis in postmortem hippocampus and cortex in schizophrenia and a comparison group. We found increased expression in the hippocampus in schizophrenia. This is the first study to demonstrate alterations in schizophrenia of an astrocytic enzyme responsible for synthesizing a neuromodulator, and further evidence that astrocytes may play a direct role in N-methyl-D-aspartate receptor dysfunction in schizophrenia.

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PubMed2006

Plasma copper, iron, ceruloplasmin and ferroxidase activity in schizophrenia.

As ceruloplasmin and copper abnormalities have been implicated in schizophrenia, we investigated the role of a second copper-containing non-ceruloplasmin protein, the iron oxidase ferroxidase II, in a prospective study of ten inpatients with schizophrenia and a comparison group. Ferroxidase II is a protein known to reciprocally regulate with ceruloplasmin in Wilson's disease, an illness characterized by psychotic symptoms, decreased ceruloplasmin, and increased copper deposition in tissues. Ferroxidase II plays a key role in the maintenance of near-normal iron metabolism in Wilson's disease, but its role in schizophrenia has never been studied. In this study, we assayed ceruloplasmin by two enzymatic assays, a standard clinical laboratory p-phenylenediamine oxidation assay and a second assay based on the rate of the oxidation and incorporation of iron (Fe3+) into transferrin; we assayed ferroxidase II activity using this second iron oxidation assay. We found that ceruloplasmin levels as measured by both enzymatic methods, but not ferroxidase II, were elevated in schizophrenia. The increased ceruloplasmin also correlated with elevated serum copper as assayed by atomic absorption spectrophotometry, which was unsurprising as the majority of copper in blood is bound to ceruloplasmin. It has been proposed that copper, as a component of several enzymes linked to dopamine synthesis, may play a role in schizophrenia by exacerbating or perpetuating dopaminergic dysregulation. Our study suggests that the ceruloplasmin elevation in schizophrenia is specific, and not simply an elevation of plasma copper-containing oxidative enzymes. Increases in ceruloplasmin may result in increased levels of copper, which ultimately proves deleterious in schizophrenia.

Adult↗

PubMed2006

Up-regulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia.

Numerous studies have described structural and functional abnormalities of the thalamus in schizophrenia, but surprisingly few studies have examined neurochemical abnormalities that accompany these pathological changes. We previously identified abnormalities of multiple molecules associated with glutamatergic neurotransmission, including changes in NMDA receptor subunit transcripts and binding sites and NMDA receptor-associated post-synaptic density (PSD) protein transcripts in the thalamus of elderly patients with schizophrenia. In the present study, we performed western blot analysis to determine whether protein levels of NMDA receptor subunits (NR1, NR2A, NR2B) and associated PSD proteins (NF-L, PSD95, SAP102) are altered in schizophrenia. Thalamic tissue from each subject was grossly dissected into two regions: a dorsomedial region containing limbic-associated dorsomedial, anterior and central medial thalamic nuclei; and a ventral thalamus region that primarily consisted of the ventral lateral nucleus. We observed increased protein expression of the NR2B NMDA receptor subunit and its associated intracellular protein, PSD95, in the dorsomedial thalamus of patients with schizophrenia, but the other molecules were unchanged, and we found no changes in the ventral thalamus. These data provide additional evidence of thalamic neurochemical abnormalities, particularly in thalamic nuclei which project to limbic regions of the brain. Further, these findings provide additional evidence of NMDA receptor alterations in schizophrenia, which may play an important role in the neurobiology of the illness.

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PubMed2006

Expression of excitatory amino acid transporter interacting protein transcripts in the thalamus in schizophrenia.

The excitatory amino acid transporters (EAATs) are a family of plasma membrane proteins that maintain synaptic glutamate concentration by removing glutamate from the synaptic cleft. EAATs are expressed by glia (EAAT1 and EAAT2) and neurons (EAAT3 and EAAT4) throughout the brain. Glutamate reuptake is regulated, in part, by EAAT-interacting proteins that modulate subcellular localization and glutamate transport activity of the EAATs. Several lines of investigation support the hypothesis of glutamatergic abnormalities in schizophrenia. Previous work in our laboratory demonstrated increased expression of EAAT1 and EAAT2 transcripts in the thalamus, suggesting that alterations in synaptic glutamate levels may contribute to the pathophysiology of schizophrenia. Since EAAT-interacting proteins regulate EAAT function, directly impacting glutamatergic neurotransmission, we hypothesized that expression of EAAT-interacting proteins may also be altered in schizophrenia. Using in situ hybridization in subjects with schizophrenia and a comparison group, we detected increased expression of JWA and KIAA0302, molecules that regulate EAAT3 and EAAT4, respectively, in the thalamus in schizophrenia. In contrast, we did not find changes in the expression of transcripts for the EAAT2 and EAAT4 regulatory proteins GPS-1 and ARHGEF11. To address prior antipsychotic treatment in our schizophrenic subjects, we treated rats with haloperidol and clozapine for 4 weeks, and found changes in transcript expression of the EAAT-interacting proteins in clozapine-, but not haloperidol-, treated rats. These findings suggest that proteins associated with the regulation of glutamate reuptake may be abnormal in this illness, supporting the hypothesis of altered thalamic glutamatergic neurotransmission in schizophrenia.

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PubMed2005

Abnormal striatal expression of transcripts encoding NMDA interacting PSD proteins in schizophrenia, bipolar disorder and major depression.

Previous studies have described abnormal expression of molecules involved in glutamatergic signaling in psychiatric illnesses, including proteins associated with receptor signaling complexes in the postsynaptic density (PSD). In particular the N-methyl-d-aspartate (NMDA) receptor complex has been associated with these illnesses. Several subcortical structures including the striatum are innervated by direct glutamatergic projections from the prefrontal cortex, and these connections may be affected in severe psychiatric illnesses. Abnormal expression of molecules critical for glutamatergic signaling in subcortical structures may thus be associated with the pathophysiology of severe psychiatric illnesses. In the present study postmortem tissue from patients with schizophrenia, bipolar disorder and major depression was used to examine striatal expression of transcripts encoding NMDA receptor interacting proteins of the PSD required for trafficking, membrane targeting and synaptic function of this receptor. We found decreased striatal expression of transcripts encoding PSD-95 and SAP-102 in bipolar disorder and of SAP-102 in major depression and schizophrenia, while no significant changes in NF--L and PSD-93 mRNAs were observed. Abnormal expression of SAP-102 in schizophrenia and SAP-102 and PSD-95 in mood disorders in subcortical structures receiving afferent glutamatergic innervation from frontal cortex suggests dysregulation of cortical-subcortical circuitry in these illnesses.

Adult↗

PubMed2005

Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia.

We investigated the expression of metabotropic glutamate receptors (mGluR) in the prefrontal cortex (PFC) and striatum in schizophrenia. mGluRs modulate the release and reuptake of synaptic glutamate and mediate some molecular correlates of neuroplasticity, including long-term potentiation. The mGluRs are expressed widely in the PFC and striatum, regions often implicated in the pathophysiology of schizophrenia. Thus, we hypothesized that abnormal expression of mGluRs might contribute to glutamatergic dysfunction observed in the PFC and striatum in schizophrenia. Accordingly, we measured the expression of metabotropic glutamate receptors (mGluRs) in Brodmann areas 9, 11, 32, and 46 in the prefrontal cortex (PFC) and the caudate, putamen, and nucleus accumbens in schizophrenia (16 cases, 9 controls) by Western blot analysis. We found an increase in the expression of mGluR1a and mGluR2/3 immunoreactivity in the PFC in schizophrenia, while no changes in the expression of mGluR4a or mGluR5 were detected in this region. In the striatum we found no changes in the expression of any of the mGluRs studied. These results suggest that alterations of mGluR1a and mGluR2/3 expression in the PFC may contribute to the pathophysiology of schizophrenia, and support targeting these receptors for the generation of novel treatment modalities for this disabling illness.

Aged↗

PubMed2005

Increased expression of glutaminase and glutamine synthetase mRNA in the thalamus in schizophrenia.

Numerous molecules enable the handling of glutamate that is destined for neurotransmitter release, including transporters, receptors and glutamatergic enzymes. Previous work in our lab has shown altered levels of transcript expression of excitatory amino acid transporters and a vesicular glutamate transporter in the thalamus in schizophrenia. These changes suggest that molecules that facilitate the release and reuptake of glutamate may be abnormal in schizophrenia. In this study we determined the levels of expression of phosphate activated glutaminase (PAG), which converts glutamine to glutamate, and glutamine synthetase (GS), which converts glutamate to glutamine, with the hypothesis that thalamic PAG and GS transcript expression is altered in schizophrenia. We investigated expression of PAG and GS mRNA using in situ hybridization in six different thalamic nuclei (anterior, dorsomedial, centromedial, ventral anterior, ventral and reticular) from 13 persons with schizophrenia and 8 comparison subjects and found that transcripts for PAG and GS were significantly increased in schizophrenia. Increased PAG and GS transcripts suggest enhanced glutamatergic neurotransmission in the thalamus and its efferent targets in schizophrenia.

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PubMed2005

Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains.

BACKGROUND: Previous studies of postmortem neurochemical markers in severe psychiatric disorders have been carried out on different brain collections, making it difficult to compare results. METHODS: One hundred RNA, protein, and other neurochemical markers were assessed in a single set of 60 postmortem brains (15 each with schizophrenia, bipolar disorder, major depression without psychosis, and unaffected control subjects) in relation to seven neurochemical systems. Quantitative measures of continuous variables for prefrontal, hippocampus, anterior cingulate, superior temporal cortex, or a combination of these were analyzed from published and unpublished studies by 56 research groups. RESULTS: Before correcting for multiple comparisons, 23% of markers (23/100) were abnormal in one or more regions, with most indicating decreased expression. The largest percentage were associated with the developmental/synaptic (10/22) and gamma-aminobutyric acid (GABA; 3/7) systems. Bipolar disorder (20) and schizophrenia (19) had the most abnormalities, with a 65% overlap. When all brain areas were considered together and corrected for multiple comparisons, reelin, parvalbumin, and GAD67 were the most abnormal. CONCLUSIONS: Confirming other studies, the GABA and developmental/synaptic neurochemical systems are promising areas for research on schizophrenia and bipolar disorder. Research should include tissue from both diseases, and additional brain areas should be assessed.

Adult↗

PubMed2005

Cortical glutamatergic markers in schizophrenia.

Post-mortem studies have yet to produce consistent findings on cortical glutamatergic markers in schizophrenia; therefore, it is not possible to fully understand the role of abnormal glutamatergic function in the pathology of the disorder. To better understand the changes in cortical glutamatergic markers in schizophrenia, we measured the binding of radioligands to the ionotropic glutamate receptors (N-methyl D-aspartate, [3H]CGP39653, [3H]MK-801), amino-3-hydroxy-5-methyl-4-isoxazole ([3H]AMPA), kainate ([3H]kainate), and the high-affinity glutamate uptake site ([3H]aspartate) using in situ radioligand binding with autoradiography and levels of mRNA for kainate receptors using in situ hybridization in the dorsolateral prefrontal cortex from 20 subjects with schizophrenia and 20 controls matched for age and sex. Levels of [3H]kainate binding were significantly decreased in cortical laminae I-II (p = 0.01), III-IV (p < 0.05), and V-VI (p < 0.01) from subjects with schizophrenia. By contrast, levels of [3H]MK-801, [3H]AMPA, [3H]aspartate, or [3H]CGP39653 binding did not differ between the diagnostic cohorts. Levels of mRNA for the GluR5 subunit were decreased overall (p < 0.05), with no changes in levels of mRNA for GluR6, GluR7, KA1, or KA2 in tissue from subjects with schizophrenia. These data indicate that the decreased number of kainate receptors in the dorsolateral prefrontal cortex in schizophrenia may result, in part, from reduced expression of the GluR5 receptor subunits.

2-Amino-5-phosphonovalerate↗

PubMed2005

Dopaminergic regulation of orexin neurons.

Orexin/hypocretin neurons in the lateral hypothalamus and adjacent perifornical area (LH/PFA) innervate midbrain dopamine (DA) neurons that project to corticolimbic sites and subserve psychostimulant-induced locomotor activity. However, it is not known whether dopamine neurons in turn regulate the activity of orexin cells. We examined the ability of dopamine agonists to activate orexin neurons in the rat, as reflected by induction of Fos. The mixed dopamine agonist apomorphine increased Fos expression in orexin cells, with a greater effect on orexin neurons located medial to the fornix. Both the selective D1-like agonist, A-77636, and the D2-like agonist, quinpirole, also induced Fos in orexin cells, suggesting that stimulation of either receptor subtype is sufficient to activate orexin neurons. Consistent with this finding, combined SCH 23390 (D1 antagonist)-haloperidol (D2 antagonist) pretreatment blocked apomorphine-induced activation of medial as well as lateral orexin neurons; in contrast, pretreatment with either the D1-like or D2-like antagonists alone did not attenuate apomorphine-induced activation of medial orexin cells. In situ hybridization histochemistry revealed that LH/PFA cells rarely express mRNAs encoding dopamine receptors, suggesting that orexin cells are transsynaptically activated by apomorphine. We therefore lesioned the nucleus accumbens, a site known to regulate orexin cells, but this treatment did not alter apomorphine-elicited activation of medial or lateral orexin neurons. Interestingly, apomorphine failed to activate orexin cells in isoflurane-anaesthetized animals. These data suggest that apomorphine-induced arousal but not accumbens-mediated hyperactivity is required for dopamine to transsynaptically activate orexin neurons.

Afferent Pathways↗

PubMed2005

Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin.

OBJECTIVE: While both thalamic abnormalities and dopaminergic dysregulation have been separately implicated in the pathophysiology of schizophrenia, little is known about the possible dysfunction of molecules associated with dopaminergic neurotransmission in the thalamus in this illness. In this study, the authors studied this question by measuring in postmortem brain the expression of molecules associated with dopaminergic neurotransmission. METHOD: Using in situ hybridization and receptor autoradiography, the authors determined in schizophrenia and comparison subjects 1) thalamic expression of the transcripts encoding the five dopamine receptors; 2) binding to the dopamine D(1), D(2), and D(3) receptors; 3) monoaminergic innervation as assessed by binding to the vesicular monoamine transporter; and 4) transcripts encoding three dopamine receptor-associated intracellular proteins (calcyon, spinophilin, and DARPP-32) that mediate integration of dopaminergic signaling with other neurotransmitter systems. RESULTS: Both calcyon and spinophilin transcripts were significantly elevated in schizophrenia subjects. Monoaminergic innervation, as well as dopamine receptor transcripts and binding sites, were unaffected in this illness. CONCLUSIONS: These data indicate that there are dopaminergic abnormalities in the thalamus in schizophrenia but that they are at the level of intracellular integration of dopamine signaling with other neurotransmitter systems, likely including glutamate, in thalamic neurons.

Aged↗

PubMed2004

Distribution of the NMDA receptor NR3A subunit in the adult pig-tail macaque brain.

The NMDA subtype of glutamate receptors are heteromeric complexes comprised of multiple subunits encoded by at least seven different genes (NR1, NR2A-2D and NR3A-3B), and differential expression of these subunits alters the pharmacological and electrophysiological properties of NMDA receptors. NR3A is a recently identified unique modulatory subunit that decreases NMDA receptor current and calcium influx. In rodents, NR3A is developmentally expressed, displaying robust expression early in development that declines with age, reaching low levels in the adult brain. A distinct and highly selective pattern of expression is observed in the developing and mature rodent brain, suggesting that NR3A may play a very specific role in NMDA receptor-mediated processes. NR3A expression in other species, however, is unknown. Therefore, we examined the expression of NR3A mRNA and protein in the adult macaque brain. Our results indicate that NR3A mRNA is expressed throughout much of the adult primate brain, and at high levels in specific brain regions including the neocortex, substantia nigra par compacta and cerebellum, as well as select areas of the hippocampus, amygdala, thalamus and hypothalamus. Western blot analysis reflects that this protein is translated and expressed in multiple brain regions. In contrast to the rat mRNA, our results suggest that NR3A transcript is widely expressed in the adult primate brain. Particular enrichment in some brain areas may reflect brain-region or circuit-specific functions for this NMDA receptor subunit.

Animals↗

PubMed2004

NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder.

Growing evidence suggests that NMDA receptor (NMDAR) dysfunction may be involved in schizophrenia. The NMDAR is a multimeric assembly derived from seven different genes (NR1, NR2A-2D and NR3A-3B). While region-specific changes in the expression of most NMDAR subunits have been reported in schizophrenia, possible abnormalities of NR3A expression have not been investigated. Both electrophysiological and anatomical data in rodents, however, suggest that NR3A subunits could play a role in this disorder. In this study, we measured NR3A transcript levels in the dorsolateral prefrontal cortex (DLPFC) and inferior temporal neocortex in the brains of people with schizophrenia, bipolar disorder, depression, and a comparison group. This transcript was elevated by 32% in schizophrenia relative to controls, but only in the DLPFC and not inferior temporal cortical regions. Interestingly, this effect was restricted to gyral aspects of the DLPFC and did not involve sulcal areas. NR3A mRNA was significantly decreased by 12% in bipolar disorder relative to the comparison group in DLPFC, although there were no gyral versus sulcal differences. As was the case in schizophrenia, no changes in NR3A expression were observed in the inferior temporal cortex in bipolar disorder. These data indicate that the NR3A subunit is abnormally expressed in both schizophrenia and bipolar disorder.

Adult↗