Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here, we report generation and characterization of Disrupted-In-Schizophrenia-1 (DISC1) genetically engineered mice as a potential model for major mental illnesses, such as schizophrenia. DISC1 is a promising genetic risk factor for major mental illnesses. In this transgenic model, a dominant-negative form of DISC1 (DN-DISC1) is expressed under the alphaCaMKII promoter. In vivo MRI of the DN-DISC1 mice detected enlarged lateral ventricles particularly on the left side, suggesting a link to the asymmetrical change in anatomy found in brains of patients with schizophrenia. Furthermore, selective reduction in the immunoreactivity of parvalbumin in the cortex, a marker for an interneuron deficit that may underlie cortical asynchrony, is observed in the DN-DISC1 mice. These results suggest that these transgenic mice may be used as a model for schizophrenia. DN-DISC1 mice also display several behavioral abnormalities, including hyperactivity, disturbance in sensorimotor gating and olfactory-associated behavior, and an anhedonia/depression-like deficit.
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PMID:Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans. 1767 7

The dopamine type-1 receptor has been implicated in major depressive disorder (MDD) by clinical and preclinical evidence from neuroimaging, post mortem, and behavioral studies. To date, however, selective in vivo assessment of D(1) receptors has been limited to the striatum in MDD samples manifesting anger attacks. We employed the PET radioligand, [(11)C]NNC-112, to selectively assess D(1) receptor binding in extrastriatal and striatal regions in a more generalized sample of MDD subjects. The [(11)C]NNC-112 nondisplaceable binding potential (BP(ND)) was assessed using PET in 18 unmedicated, currently depressed subjects with MDD and 19 healthy controls, and compared between groups using MRI-based region-of-interest analysis. The mean D(1) receptor BP(ND) was reduced (14%) in the left middle caudate of the MDD group relative to control group (p<0.05). Among the MDD subjects D(1) receptor BP(ND) in this region correlated negatively with illness duration (r=-0.53; p=0.02), and the left-to-right BP(ND) ratio correlated inversely with anhedonia ratings (r=-0.65, p=0.0040). The D(1) receptor BP(ND) was strongly lateralized in striatal regions (p<0.002 for main effects of hemisphere in accumbens area, putamen, and caudate). In post hoc analyses, a group-by-hemisphere-by-gender interaction was detected in the dorsal putamen, which was accounted for by a loss of the normal asymmetry in depressed women (F=7.33, p=0.01). These data extended a previous finding of decreased striatal D(1) receptor binding in an MDD sample manifesting anger attacks to a sample selected more generally according to MDD criteria. Our data also more specifically localized this abnormality in MDD to the left middle caudate, which is the target of afferent neural projections from the orbitofrontal and anterior cingulate cortices where neuropathological changes have been reported in MDD. Finally, D(1) receptor binding was asymmetrical across hemispheres in healthy humans, compatible with evidence that dopaminergic function in the striatum is lateralized during reward processing, voluntary movement, and self-stimulation behavior.
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PMID:Dopamine type-1 receptor binding in major depressive disorder assessed using positron emission tomography and [11C]NNC-112. 1894 69

Two human associative-learning experiments investigated the relationship between the negative dimension of schizotypy and selective and nonselective prediction-error learning. Experiment 1 demonstrates that individuals low, but not high, on the introvertive anhedonia dimension of schizotypy demonstrate Kamin blocking, which has been taken to reflect the operation of selective learning (Rescorla & Wagner, 1972). In complement, Experiment 2 demonstrates that individuals high, but not low, on the same dimension demonstrate asymmetrical learning about the components of a compound stimulus that differ in their associative history, which has been suggested to reflect the operation of nonselective learning (Rescorla, 2000). The implications of this double dissociation for understanding the nature of the cognitive deficit in schizophrenia and for theories of learning are considered.
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PMID:Variations in selective and nonselective prediction error with the negative dimension of schizotypy. 2050 8