The insulin receptor substrate-4 (IRS-4) gene and schizophrenia: no evidence for a main genetic factor, however one report of a single schizophrenia patient with a mutation.

OBJECTIVES: Since there are clear indications that schizophrenia is a systemic disorder, we sought for a common molecular basis for schizophrenia abnormalities in brain and body. Our hypothesis was that an impaired insulin/ insulin-like growth factor signalling in cells might underlie both structural and functional brain changes and peripheral abnormalities in schizophrenia. No associations between polymorphisms in the genes for insulin-like growth factor 1 or its receptor and schizophrenia have been reported. However, the insulin receptor substrates 1-4 linking both the insulin and insulin-like growth factor 1 receptors with intracellular pathways have not been extensively studied in schizophrenia. In this study, we therefore chose to study the insulin receptor substrate-4 (IRS-4) gene as a candidate gene in schizophrenia. METHODS: The IRS-4 gene of 93 patients and 59 control subjects was screened for DNA sequence variations, followed by case-control analyses of 10 detected single nucleotide polymorphisms. RESULTS: No significant genotype, allele or haplotype associations were found with the schizophrenia illness. However, one female patient with paranoid schizophrenia had an IRS-4 gene mutation at position 107863596, resulting in a change in amino acid coding from histidine to tyrosine at position 879. CONCLUSIONS: Although this study supports the view that the IRS-4 gene is not of major importance for the aetiology of the vast majority of schizophrenia cases, our finding of this single patient with schizophrenia and a mutation in the IRS-4 gene may point to that the insulin/ insulin-like growth factor signalling system in cells is still of interest in the future search for schizophrenia genes.

Bacterial kidney disease as a model for studies of cell mediated immunity in rainbow trout (Oncorhynchus mykiss).

A cell mediated immune (CMI) response was measured in vitro to heat-killed and to paraformaldehyde fixed Renibacterium salmoninarum (Rs) in rainbow trout (Oncorhynchus mykiss) experimentally challenged with live Rs. The mitogenic response to the T lymphocyte mitogen Concanavalin A (Con A) was reduced during samplings 4 to 6 weeks after immersion, but no effect of the response to the B lymphocyte mitogen lipopolysaccharide (LPS) was detected. The subpopulation of lymphocytes, detected by the monoclonal antibody 1C2, was decreased from the 4th week to the 5th week of infection, and remained at the decreased level up to 10 weeks post immersion. The proportion of Immunoglobulin (Ig) bearing lymphocytes was not affected during the Rs infection period. The humoral antibody level to heat-stable Rs-antigens was increased up to 10 weeks after immersion but after 27 weeks was reduced to a level similar to that of the non-challenged fish. An anamnestic response was demonstrated in challenged fish, as intraperitoneal injection of heat-treated Rs bacteria into Rs challenged fish elicited a stronger humoral antibody response compared with injection into non-challenged fish.