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

Subjects with schizophrenia (SZ) have an increased density of synapses characteristic of corticostriatal or thalamostriatal glutamatergic inputs in the caudate matrix and putamen patches. SZ is a heterogeneous disease in many aspects including symptoms. The purpose of the present study was to determine if the synaptic organization in two different DSM-i.v. subgroups of SZ was differentially affected. Postmortem striatal tissue was obtained from the Maryland Brain Collection from normal controls (NC), chronic paranoid SZs (SZP), and chronic undifferentiated SZs (SZU). Tissue was prepared for calbindin immunocytochemistry to identify patch matrix compartments, prepared for electron microscopy and analyzed using stereological methods. The synaptic density of asymmetric synapses, characteristic of glutamatergic inputs, was elevated equivalently in striatal patches in the SZP and SZU versus NC. The SZU also had an increased density of asymmetric synapses in the striatal matrix compared to NC. Moreover, symmetric axospinous synapses, characteristic of intrinsic inhibitory inputs and dopaminergic afferents, showed a dichotomy in synaptic density between the SZU and SZP in the striatal and caudate matrix. These data show discreet differences in synaptic organization between SZU and SZP and/or NCs. The results suggest that abnormal corticostriatal and/or corticothalamic inputs to striatal patches may be related to limbic dysfunction, which is perturbed in both subtypes of SZ. The selective increase in axospinous synapses in the matrix of the SZU subgroup compared to the SZP may be related to more severe cognitive problems in that subset of SZ compared to SZP.
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PMID:Differential synaptic changes in the striatum of subjects with undifferentiated versus paranoid schizophrenia. 1850 52

Schizophrenia (SZ) is a heterogeneous disease with a spectrum of symptoms, risk factors, and etiology. Abnormalities in mitochondria, the energy-producing organelles of the cell, have been observed in mixed cohorts of subjects with SZ. The purpose of the present study was to determine if striatal mitochondria were differentially affected in two different DSM-IV subgroups of SZ. Postmortem striatal tissue was examined from normal controls (NC), chronic paranoid SZs (SZP), and chronic undifferentiated SZs (SZU). Tissue was processed for calbindin immunohistochemistry to identify striosomal compartments, prepared for electron microscopy and analyzed using stereological methods. In both caudate and putamen, the density of mitochondria in the neuropil was decreased in SZP compared to both NCs and SZU. In the putamen, both the SZP and the SZU subgroups had fewer mitochondria per synapse than did NCs. When examining patch matrix compartments, striatal compartments associated with different circuitry and function, only the matrix exhibited changes. In the caudate matrix, the SZP subgroup had fewer mitochondria in the neuropil than did the SZU and NCs. In the putamen matrix, the SZP had fewer mitochondria in the neuropil as compared to NCs, but not the SZU. The numbers of mitochondria per synapse in both the SZP and the SZU groups were similar to each other and fewer than that of NCs. A decrease in mitochondrial density in the neuropil distinguishes the SZP from the SZU subgroup, which could be associated with the symptoms of paranoia and/or could represent a protective mechanism against some of the symptoms that are less pronounced in this subtype than in the SZU subgroup such as cognitive and emotional deficits.
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PMID:Striatal mitochondria in subjects with chronic undifferentiated vs. chronic paranoid schizophrenia. 2246 Jul 19

Global deficits in declarative memory are commonly reported in individuals with schizophrenia and psychotic bipolar disorder, and in their biological relatives. However, it remains unclear whether there are specific components within the global declarative memory dysfunction that are unique to schizophrenia and bipolar disorder, or whether these impairments overlap the two psychoses. This study sought to characterize differential components of learning and memory in individuals within the psychosis dimension: probands with schizophrenia (SZP, n=33), probands with psychotic bipolar I disorder (BDP, n=20), and biological relatives of SZP (SZR, n=21), contrasted with healthy controls (HC, n=26). A computerized cognitive paradigm, the Acquired Equivalence test, with probes for associative learning, memory for learned associations, and memory generalization was administered, along with standardized neuropsychological measures of declarative memory. All study groups were able to learn and remember the associations, although SZP were slower than HC in the initial learning stages. Both SZP (significantly) and BDP (at a trend level) showed altered memory generalization compared to HC (SZP vs. HC, p=.038, d=.8; BDP vs. HC, p=.069, d=.95). SZR showed memory generalization intermediate between SZP and HC, although their performance did not differ significantly from either group. These findings indicate that probands with schizophrenia and bipolar psychoses have similar alteration in the ability to flexibly generalize learned knowledge when probed with novel stimuli, despite overall sufficient associative learning and memory for what they learned. These results suggest that the two disorders present a clinical continuum with overlapping hippocampus-mediated memory generalization dysfunction underlying the psychosis phenotype.
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PMID:Memory generalization is selectively altered in the psychosis dimension. 2255 81

Movement sequencing difficulties are part of the neurological soft signs (NSS), they have high clinical value because they are not always present in schizophrenia. We investigated the neuronal correlates of movement sequencing in 24 healthy controls and 24 schizophrenia patients, with (SZP SQ+) or without (SZP SQ-) sequencing difficulties. We characterized simultaneous and lagged functional connectivity between brain regions involved in movement sequencing using psychophysiological interaction (PPI) and the Granger causality modeling (GCM), respectively. Left premotor cortex (PMC) and superior parietal lobule (SPL) were specifically activated during sequential movements in all participants. Right PMC and precuneus, ipsilateral to the hand executing the task, activated during sequential movements only in healthy controls and SZP SQ-. SZP SQ+ showed hyperactivation in contralateral PMC, as compared to the other groups. PPI analysis revealed a deficit in inhibitory connections within this fronto-parietal network in SZP SQ+ during sequential task. GCM showed a significant lagged effective connectivity from right PMC to left SPL during task and rest periods in all groups and from right PMC to right precuneus in SZP SQ+ group only. Both SZP groups had a significant lagged connectivity from right to left PMC, during sequential task. Our results indicate that aberrant fronto-parietal network connectivity with cortical inhibition deficit and abnormal reliance on previous network activity are related to movement sequencing in SZP. The overactivation of motor cortex seems to be a good compensating strategy, the hyperactivation of parietal cortex is linked to motor deficit symptoms.
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PMID:Neuronal substrate and effective connectivity of abnormal movement sequencing in schizophrenia. 2678 Jun 3

The fronto-striato-thalamic circuitry is a key network in patients with schizophrenia (SZPs). We use diffusion tensor imaging (DTI) to investigate the integrity of white matter (WM) pathways involved in this network in SZPs relative to healthy controls (HCs). We also evaluate the differential impact of chronic exposure to clozapine as well as other atypical and typical antipsychotics. 63 HCs and 41 SZPs were included. Of the SZPs, 16 were treated with clozapine (SZPsC), 17 with atypical antipsychotics (SZPsA), and 8 with typical antipsychotics (SZPsT). Three tracts were reconstructed in the left hemisphere using tractography: one fronto-subcortical tract, one prefronto-subcortical tract, and one prefronto-frontal tract. Diffusion parameters were individually extracted in each tract. SZPs exhibited lower integrity in both the fronto-subcortical and prefronto-subcortical tracts relative to HCs, and SZPsT showed altered integrity compared to SZPsC. There were no WM integrity differences in the prefronto-frontal tract between SZP groups or between SZPs and HCs. SZPs exhibit structural connectivity abnormalities in the prefronto-fronto-subcortical network that are specifically and differentially impacted by the type of antipsychotic treatment. Additional studies are needed to separate the contributions of clozapine-mediated neuroprotection, neurotoxicity related to typical antipsychotics, and the illness itself to observed differences.
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PMID:Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study. 3014 82

One deficit associated with schizophrenia (SZ) is the reduced ability to distinguish self-caused sensations from those due to external sources. This reduced sense of agency (SoA, subjective awareness of control over one's actions) is hypothesized to result from a diminished utilization of internal monitoring signals of self-movement (i.e., efference copy) which subsequently impairs forming and utilizing sensory prediction errors (differences between the predicted and actual sensory consequences resulting from movement). Another important function of these internal monitoring signals is the facilitation of higher-order mechanisms related to motor learning and control. Current predictive-coding models of adaptation postulate that the sensory consequences of motor commands are predicted based on internal action-related information, and that ownership and control of motor behavior is modified in various contexts based on predictive processing. Here, we investigated the connections between SoA and motor adaptation. Schizophrenia patients (SZP, N=30) and non-psychiatric control subjects (HC, N=31) adapted to altered movement visual feedback and applied the motor recalibration to untested contexts (i.e., the spatial generalization). Although adaptation was similar for SZP and controls, the extent of generalization was significantly less for SZP; movement trajectories made by patients to the furthest untrained target (135o) before and after adaptation were largely indistinguishable. Interestingly, deficits in generalization were correlated with positive symptoms of psychosis in SZP (e.g., hallucinations). Generalization was also associated with measures of SoA across both SZP and HC, emphasizing the role action awareness plays in motor behavior, and suggesting that misattributing agency, even in HC, manifests in abnormal motor performance.
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PMID:Reduced transfer of visuomotor adaptation is associated with aberrant sense of agency in schizophrenia. 3122 88