Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combining in situ radioligand binding with autoradiography, we previously identified a reduction of [(3)H]phorbol 12,13-dibutyrate binding in the parahippocampal gyrus from schizophrenic subjects. To determine whether these changes were due to decreases in the level of protein kinase C, we measured [(3)H]phorbol 12,13-dibutyrate binding, levels of the protein kinase C isoforms alpha, beta, delta, epsilon, gamma, eta and theta, as well as protein kinase C activity in crude particulate membranes from parahippocampal gyri of 15 schizophrenic and 15 control subjects. There was a significant decrease in the density (mean +/- SEM: 6.56 +/- 0.73 pmol mg(-1) vs 9.68 +/- 1.22 pmol mg(-1); P < 0.05) and affinity (mean K(D) +/- SEM: 4.64 +/- 0.34 nM vs 2.95 +/- 0.35 nM; P < 0.005) of [(3)H]phorbol 12,13-dibutyrate binding in homogenates from schizophrenic subjects. There were no significant changes in levels of the protein kinase C isoforms which are known to bind phorbol esters or in the activity of protein kinase C in membranes from schizophrenic subjects. These results suggest that there are changes in molecules capable of binding [(3)H]phorbol 12,13-dibutyrate, other than protein kinase C, in the parahippocampal gyrus from subjects with schizophrenia.
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PMID:Decreased phorbol ester binding in the parahippocampal gyrus from subjects with schizophrenia is not associated with changes in protein kinase C. 1219 11

Mounting evidence suggests that schizophrenia is a neurodevelopmental disease resulting in dysfunctional connectivity between various brain regions. Retinoid pathway dysregulation has been proposed as a potentially important factor in the etiology of schizophrenia. Retinoid signaling plays a central role in many aspects of development, ranging from neurogenesis to activity-dependent plasticity, and regulates the expression of many candidate genes for schizophrenia. The retinoid pathway acts through two families of nuclear receptors highly expressed in the hippocampus, the retinoic acid (RAR) and retinoid X (RXR) receptors, both existing in three different subtypes (alpha, beta and gamma) and several isoforms. The present study examines the expression of the retinoid receptors in the dentate gyrus of schizophrenia and nonpsychiatric controls. The proportion of granule cells of the dentate gyrus expressing RAR(alpha) is increased by twofold in schizophrenia, while the proportion of cells expressing RAR(gamma)1 and 2, as well as RXR(beta) and gamma, is unchanged. These results demonstrate a dysregulation in the expression of at least one member of the RAR family of retinoid receptors in schizophrenia. Understanding the basis for this and how it affects downstream molecular pathways associated with hippocampal plasticity may provide insight into the dysfunctional connectivity of schizophrenia.
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PMID:The expression of retinoic acid receptor alpha is increased in the granule cells of the dentate gyrus in schizophrenia. 1569 73

Calcineurin (protein phosphatase 2B) is a calcium-dependent serine-threonine phosphatase. It has diverse roles and is centrally involved in synaptic plasticity. The catalytic A subunit of calcineurin has three isoforms, alpha, beta and gamma. Their expression and ontogeny in the brain has not been systematically investigated; such data become important with a report that PPP3CC, the gene encoding calcineurin Agamma, is a susceptibility gene for schizophrenia, and the finding that its expression is decreased in the disorder. We used in situ hybridization histochemistry to measure the relative transcript abundance of calcineurin Agamma and the other catalytic isoforms, Aalpha and Abeta, during development of the Sprague-Dawley rat hippocampus and cerebellum. All three isoforms are present in both regions at all time points [embryonic day 19 (E19) to postnatal day 42 (P42)] and undergo developmental regulation, but differ in their ontogenic profile. Calcineurin Aalpha and Abeta mRNAs increased from E19 through to adulthood, whereas Agamma mRNA was most highly expressed during early developmental stages. Calcineurin Aalpha and Abeta mRNAs positively correlated with synaptophysin mRNA (a synaptic marker), whilst Agamma mRNA was either unrelated to, or negatively correlated, with this transcript. These data confirm that all three calcineurin A subunits are expressed in the rodent brain, and indicate that calcineurin Agamma may have different roles than Aalpha and Abeta. The data also suggest a potential importance of calcineurin Agamma in neurodevelopment, and in the genetically influenced neurodevelopmental disturbance that is thought to underlie schizophrenia.
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PMID:Differential expression of calcineurin A subunit mRNA isoforms during rat hippocampal and cerebellar development. 1636 68

Disturbances in "functional connectivity" have been proposed as a major pathophysiological mechanism for schizophrenia, and in particular, for cognitive disorganization. Detection and estimation of these disturbances would be of clinical interest. Here we characterize the spatial pattern of functional connectivity by computing the "synchronization likelihood" (SL) of EEG at rest and during performance of a 2Back working memory task using letters of the alphabet presented on a PC screen in subjects with schizophrenia and healthy controls. The spatial patterns of functional connectivity were then characterized with graph theoretical measures to test whether a disruption of an optimal spatial pattern ("small-world") of the functional connectivity network underlies schizophrenia. Twenty stabilized patients with schizophrenia, who were able to work, and 20 healthy controls participated in the study. During the working memory (WM) task healthy subjects exhibited small-world properties (a combination of local clustering and high overall integration of the functional networks) in the alpha, beta and gamma bands. These properties were not present in the schizophrenia group. These findings are in accordance with a partially inadequate organization of neuronal networks in subjects with schizophrenia. This method could be helpful for diagnosis and evaluation of the severity of the disease, as well as understanding the pathophysiologic mechanisms underlying cognitive dysfunction in schizophrenia.
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PMID:Small-world networks and disturbed functional connectivity in schizophrenia. 1687 1

Previous studies have shown alterations of eyeblink reflex in patients with various psychiatric disorders. It has previously been demonstrated by our group that EEG measures of the reactivity to eye opening could effectively predict patient-reported startle response in patients with acute stress reaction. In our present study, EEG spectral power analysis and eyeblink electrical startle responses were acquired from a total of 39 patients diagnosed with various psychiatric disorders: 7 patients with schizophrenia, 10 patients with major depressive disorder (MDD), 10 patients with panic disorder, 5 patients with posttraumatic stress disorder (PTSD) and 7 patients with generalized anxiety disorder (GAD). EEG percent power data of each frequency band (delta, theta, alpha, beta) obtained from the 19 leads under open or closed eyelid conditions were used to calculate the arithmetical difference between eyes-open and eyes-closed states as representative of "EEG reactivity to eye opening". Data was analyzed separately for each diagnostic group. For all of the disorders, right-sided R2c (contralateral secondary component) latency was the single eyeblink startle measure that was found to be significantly correlated with EEG reactivity to eye opening. The correlation was most significant for right temporal theta frequency in schizophrenia, right temporal theta frequency in MDD, left central beta frequency in panic disorder, left parietotemporal delta frequency in PTSD and right occipital alpha frequency in GAD. Findings showed a newly identified pattern that has potential scientific and clinical value with respect to psychiatric medicine.
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PMID:EEG correlates of startle reflex with reactivity to eye opening in psychiatric disorders: preliminary results. 1692 10

The serine/threonine kinase, protein kinase B (PKB, also known as Akt), is activated by a wide array of growth factors and insulin. PKB is a central player in the regulation of metabolism, apoptosis, transcription and the cell-cycle. PKB exists as three isoforms (alpha, beta and gamma) that may have unique as well as common functions within the cell. Deregulation of PKB is associated with several human diseases, including cancer, diabetes and schizophrenia. These findings underscore the medical relevance of the PKB pathway and make PKB an attractive drug target for the treatment of diseases that exhibit abnormal PKB signalling.
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PMID:Protein kinase B: signalling roles and therapeutic targeting. 1795 68

Cadherins and protocadherins are cell adhesion proteins that play an important role in neuronal migration, differentiation and synaptogenesis, properties that make them targets to consider in schizophrenia (SZ) and bipolar disorder (BD) pathogenesis. Consequently, allelic variation occurring in protocadherin and cadherin encoding genes that map to regions of the genome targeted in SZ and BD linkage studies are particularly strong candidates to consider. One such set of candidate genes is the 5q31-linked PCDH family, which consists of more than 50 exons encoding three related, though distinct family members--alpha, beta, and gamma--which can generate thousands of different protocadherin proteins through alternative promoter usage and cis-alternative splicing. In this study, we focused on a SNP, rs31745, which is located in a putative PCDHalpha enhancer mapped by ChIP-chip using antibodies to covalently modified histone H3. A striking increase in homozygotes for the minor allele at this locus was detected in patients with BD. Molecular analysis revealed that the SNP causes allele-specific changes in binding to a brain protein. The findings suggest that the 5q31-linked PCDH locus should be more thoroughly considered as a disease-susceptibility locus in psychiatric disorders.
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PMID:Analysis of protocadherin alpha gene enhancer polymorphism in bipolar disorder and schizophrenia. 1850 41

Transliminality reflects individual differences in the threshold at which unconscious processes or external stimuli enter into consciousness. Individuals high in transliminality possess characteristics such as magical ideation, belief in the paranormal, and creative personality traits, and also report the occurrence of manic/mystic experiences. The goal of the present research was to determine if resting brain activity differs for individuals high versus low in transliminality. We compared baseline EEG recordings (eyes-closed) between individuals high versus low in transliminality, assessed using The Revised Transliminality Scale of Lange et al. (2000). Identifying reliable differences at rest between high- and low-transliminality individuals would support a predisposition for transliminality-related traits. Individuals high in transliminality exhibited lower alpha, beta, and gamma power than individuals low in transliminality over left posterior association cortex and lower high alpha, low beta, and gamma power over the right superior temporal region. In contrast, when compared to individuals low in transliminality, individuals high in transliminality exhibited greater gamma power over the frontal-midline region. These results are consistent with prior research reporting reductions in left temporal/parietal activity, as well as the desynchronization of right temporal activity in schizotypy and related schizophrenia spectrum disorders. Further, differences between high- and low-transliminality groups extend existing theories linking altered hemispheric asymmetries in brain activity to a predisposition toward schizophrenia, paranormal beliefs, and unusual experiences.
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PMID:The transliminal brain at rest: baseline EEG, unusual experiences, and access to unconscious mental activity. 1881 70

In this work, we attempt to extend to the schizophrenia's research the evidence that different frequency bands may emerge from different sources during early-stage visual processing, in a mental state-specific manner, while subjects are passively viewing a visual stimulus. We applied standard pattern reversal stimulation (checker-board), a task with low cognitive demands, coupled to a dense EEG recording system to estimate the neural correlates of the evoked theta, alpha, beta, beta1, and gamma frequency band responses by means of brain electrical tomography (BET). After filtering the evoked activity using different band-passes, a very different picture about the current sources during P100 will emerge. The results showed notable differences between the two groups. In healthy subjects we localized the significances in the anterior cingulate, caudate nucleus, thalamus, precuneous region, and superior parietal that were more active for gamma band. In patients with schizophrenia differences occupy the hippocampus, parahippocampus, thalamus, midbrain, precuneus, and superior parietal regions. Most areas were more active for gamma band except precuneous and superior parietal region more active for theta and alpha frequency band. These sets of regions, in both groups, reflect events that are parallel to and partly independent of the P100 component, while in the schizophrenia, these regions have been previous linked to the major symptoms of the disease. We concluded that this result provides important evidence indicating that the proposed method is able to differentiate electrophysiological patterns in healthy subjects from those in patients with schizophrenia.
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PMID:BET differences among simultaneous evoked frequency band responses during early-stage visual processing distinguish schizophrenia from healthy subjects. 1902 20

Gamma (gamma) oscillations (30-50 Hz) elicited during working memory (WM) are altered in schizophrenia (SCZ). However, the nature of the relationship between evoked frontal oscillatory activity, WM performance and symptom severity has yet to be ascertained. This study had two objectives. First, to extend previous studies by examining delta, theta, alpha, beta, and gamma (delta, theta, alpha, beta, and gamma) oscillatory activities during the N-back task in SCZ patients compared to healthy subjects; second, to evaluate the relationship between oscillatory activities elicited during the N-back, performance, and clinical symptoms in SCZ patients. Patients with SCZ elicited excessive frontal gamma oscillatory activity that was most pronounced in the 3-back condition compared to healthy subjects. Reduced frontal beta activity at all WM loads was also observed in patients with SCZ compared to healthy subjects. Task performance was inversely correlated with negative symptoms but not with positive symptoms. Our findings suggest that evoked frontal oscillatory activities during WM are selectively altered in the gamma and beta frequency bands that may contribute to WM impairment in SCZ patients. These findings may provide important insights into the pathophysiology underlying WM deficits, its relationship to negative symptoms and may represent a potential neurobiological marker for cognitive enhancing strategies in SCZ.
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PMID:Evidence for excessive frontal evoked gamma oscillatory activity in schizophrenia during working memory. 2059 57


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