preproenkephalin and Schizophrenia

To investigate the correlation between single nucleotide polymorphisms (SNPs) of functional candidate gene Prodynorphin (PDYN) and schizophrenia.. SNPs in the promoter and exon regions of PDYN were screened and genotyped for association study in a cohort of Chinese Han schizophrenia cases and controls.. Two SNPs PDYN-1576C>T and PDYN-946C>G were identified in the promoter region but PDYN-946C>G showed significant differences of allele distribution (x2=6.15, P=0.013) and genotype distribution (x2=6.87, P=0.032) between schizophrenic and control subjects.. PDYN-946C>G polymorphism demonstrated an association with population susceptibility to schizophrenia.

Topics: Adult; Asian People; Enkephalins; Exons; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Protein Precursors; Schizophrenia

Experimental and clinical studies suggest an involvement of the opioid neuropeptide system in schizophrenia. In particular, the prodynorphin (PDYN), the precursor of the dynorphin opioid peptides, has been shown to play an important role in several aspects of human mental diseases. Recently, a functional polymorphism in the promoter of PDYN gene has been described. We studied the possible relationship between this polymorphism and schizophrenia and we found no significant difference in allelic and genotype distributions between schizophrenic patients and control subjects. However, we observed a significant interactive effect with the receptor 3 of dopamine gene (DRD3); in particular, the frequency of subjects carrying PDYN allele 3 being also homozygotes for DRD3 Gly allele (of Ser9Gly polymorphism) was significantly greater in patients than controls. We conclude that PDYN gene polymorphism alone does not alter the risk for schizophrenia but, by an epistatic interaction with the Gly allele of DRD3 gene, may contribute to the susceptibility to this disorder.

Topics: Alleles; Case-Control Studies; Enkephalins; Genetic Variation; Genotype; Glycine; Humans; Italy; Polymorphism, Genetic; Promoter Regions, Genetic; Protein Precursors; Receptors, Dopamine D2; Receptors, Dopamine D3; Risk Factors; Schizophrenia; White People

The dynorphin system has been associated with the regulation of mood. The expression of the prodynorphin mRNA was currently studied in the amygdaloid complex, a brain region critical for emotional processing, in subjects (14-15 per group) diagnosed with major depression, bipolar disorder, or schizophrenia and compared to normal controls. In situ hybridization histochemistry was used to characterize the anatomical distribution and expression levels of the prodynorphin mRNA within the amygdaloid complex. High prodynorphin mRNA levels were expressed in the parvicellular division of the accessory basal, posterior cortical, periamygdaloid cortex, and amygdalohippocampal area in normal subjects. Individuals with major depression had significantly reduced (41-68%) expression of the prodynorphin mRNA in the accessory basal (both parvicellular and magnocellular divisions; P < 0.01) and amygdalohippocampal area (P < 0.001) as compared to controls. The bipolar disorder group also showed a significant reduction (37-38%, P < 0.01) of the mRNA expression levels in the amygdalohippocampal area and in the parvicellular division of the accessory basal. No other amygdala nuclei studied showed any significant differences for the prodynorphin mRNA levels measured in the major depression and bipolar disorder subjects. Additionally, the prodynorphin mRNA expression levels did not differ significantly between the schizophrenic and normal control subjects in any of the amygdala areas examined. These findings indicate specific prodynorphin amygdala impairment in association with mood disorder.

Topics: Adult; Affect; Aged; Amygdala; Bipolar Disorder; Depressive Disorder, Major; Enkephalins; Female; Gene Expression Profiling; Hippocampus; Humans; In Situ Hybridization; Male; Middle Aged; Nerve Tissue Proteins; Protein Precursors; RNA, Messenger; Schizophrenia

The present study examined the prodynorphin and kappa opioid receptor mRNA expression levels in the anterior cingulate and dorsolateral prefrontal cortices of subjects diagnosed with schizophrenia, bipolar disorder, or major depression as compared with normal controls without a psychiatric diagnosis. Multivariate analyses failed to reveal any differences in the mRNA expression levels between the four diagnostic groups, though a group trend (non-significant) was evident for the expression of the kappa opioid receptor and prodynorphin mRNAs in the prefrontal cortex. The mRNA expression levels were not associated with lifetime history of antipsychotic treatment or with suicide as a cause of death. The results, however, suggested an influence of certain drugs of abuse on the prodynorphin cortical mRNA expression. Prodynorphin mRNA expression levels were found to be elevated in individuals with a history of marihuana or stimulant use, but not alcohol. Overall, our data do not provide strong evidence for impaired prodynorphin or kappa opioid receptor mRNA levels in the dorsolateral prefrontal or cingulate cortices of schizophrenic, bipolar disorder, or major depressed subjects.

Topics: Adult; Age Factors; Amphetamine-Related Disorders; Bipolar Disorder; Depressive Disorder, Major; Enkephalins; Female; Functional Laterality; Humans; In Situ Hybridization; Male; Marijuana Abuse; Middle Aged; Protein Precursors; Receptors, Opioid, kappa; RNA, Messenger; Schizophrenia; Sex Factors; Suicide

Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD.

Topics: Adult; Alzheimer Disease; Antibodies; Antibody Formation; Autoimmunity; Binding, Competitive; Enkephalins; Enzyme-Linked Immunosorbent Assay; Female; HIV Seropositivity; Humans; Male; Multiple Sclerosis; Obsessive-Compulsive Disorder; Protein Precursors; Schizophrenia; Somatostatin