The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.

There has been a marked convergence of the gender gap in discharge diagnosis of alcohol use disorder among psychiatric in-patients in Iceland over the last decades. For other substance use disorders, the change was not as pronounced. Our results emphasize the importance of monitoring changes in substance use disorder diagnosis as this may uncover different treatment needs in this group of vulnerable individuals.

SUD was the psychiatric diagnosis that had the highest mortality rate among psychiatric inpatients, in both men and women. An additional psychiatric diagnosis on a pre-existing SUD diagnosis did increase the risk for men but not women.

Risk of mortality and criminal trends among psychiatric inpatients can be described as distinct clusters of risk factors present at first admission to a psychiatric hospital. Treatment and interventions to reduce mortality and criminality should take these risk differences into account.