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)

The Chromosome 5 Workshop heard new data on a schizophrenia susceptibility locus in the 5q23.3-q31.1 region. Sixty-two pedigrees from Finland gave a lod score of 1.36 at the CSF1R locus approximately 14 cM distal to IL9/D5S393, where positive results from three pedigree collections converged at the 1997 workshop. Though positive at CSF1R, the new data were only weakly positive at the IL9 (lod 0.46) and D5S393 (lod 0.07) loci themselves. The workshop also reviewed new evidence in the 5p14.1-p13.1 region, where a large pedigree of schizophrenia of Puerto Rican extraction has suggested a susceptibility locus with a maximum lod score at D5S111. Twenty-one new pedigrees multiplex for schizophrenia in African Americans gave positive lod scores at D5S111 and flanking loci. In bipolar illness five genetically related pedigrees from the Saguenay-Lac-St. Jean region of Quebec identified a region of interest at 5q31.3-q35.1. This region overlaps with the D5S423 locus and includes the D5S812 locus and the 5q34 region, all of which are consistent with linkage in at least one other study.
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PMID:Report of the Chromosome 5 Workshop of the Sixth World Congress on Psychiatric Genetics. 1037 36

Prepulse inhibition (PPI), the reduction in acoustic startle produced when it is preceded by a weak prepulse stimulus, is impaired in schizophrenic patients. The DBA/2J mouse strain displayed deficient PPI and is therefore suggested as an experimental animal model for the loss of sensorimotor gating in schizophrenia. Brain serotonin (5-HT) has been implicated in the pathophysiology of several psychiatric disorders, including major depressive disorder and schizophrenia. In the present study, behavior, 5-HT transporter (5-HTT) mRNA level, 5-HT(1A) receptor mRNA level, and 5-HT(1A) receptor density in the brain regions were studied in DBA/2J mice in comparison with four inbred mouse strains (CBA/Lac, C57BL/6, BALB/c, and ICR). A decrease in 5-HTT mRNA level in the midbrain and a reduced density of 5-HT(1A) receptors in the frontal cortex without significant changes in 5-HT(1A) receptor mRNA level in DBA/2J mice were found. It was shown that, along with decreased PPI, DBA/2J mice demonstrated considerably reduced immobility in the tail suspension test and in the forced swim test. No significant interstrain differences in intermale aggression, or in light-dark box and elevated plus-maze tests, were found. The results suggested the involvement of decreased 5-HTT gene expression and 5-HT(1A) receptor density in genetically defined PPI deficiency and showed a lack of any association between PPI deficiency and predisposition to aggressive, anxiety, and depressive-like behaviors.
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PMID:Serotonin transporter, 5-HT1A receptor, and behavior in DBA/2J mice in comparison with four inbred mouse strains. 1953 37

Dysfunction in brain serotonin (5-HT) system has been implicated in the psychopathology of anxiety, depression, drug addiction, and schizophrenia. The 5-HT(1A) receptors play a central role in the control of 5-HTergic neurotransmission. There are some scarce data showing cross-regulation between 5-HT receptors. Here, we investigated whether interaction exists between 5-HT(1A) receptor and genes encoding key members in brain 5-HT system. Chronic treatment with selective agonist of 5-HT(1A) receptor 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.0 mg/kg i.p., 14 days) produced considerable decrease in hypothermic response to acute administration of 8-OH-DPAT in CBA/Lac mice indicating desensitization of 5-HT(1A) receptors. The decrease in 5-HT(1A) gene expression as well as decrease in the expression of gene encoding key enzyme in 5-HT synthesis, tryptophan hydroxylase-2 (TPH-2) in the midbrain, and the expression of the gene encoding 5-HT(2A) receptor in the frontal cortex was shown. There were no significant changes in 5-HT transporter mRNA level in the midbrain. Despite considerable decrease in the expression of the genes encoding tryptophan hydroxylase-2, 5-HT(1A) and 5-HT(2A) receptors, chronic 8-OH-DPAT treatment failed to produce significant changes in 5-HT(1A)-linked behavior (intermale aggression, open-field behavior, light-dark box, and pinch-induced catalepsy), suggesting compensatory and adaptive effect of genes suppression. The obtained data on the effect of 8-OH-DPAT-induced desensitization of 5-HT(1A) receptors on 5-HT(1A), 5-HT(2A) and TPH-2 gene expression demonstrated the role of 5-HT(1A) receptor as indirect regulator of gene expression. The results provide the first evidence of receptor-key genes interaction in brain 5-HT system and may have profound implications in understanding the functioning of the brain neurotransmitter systems.
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PMID:Receptor-genes cross-talk: effect of chronic 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino) tetralin treatment on the expression of key genes in brain serotonin system and on behavior. 2042 22