Suicide risk in schizophrenia: learning from the past to change the future

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures. This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Additional support for schizophrenia linkage on chromosomes 6 and 8: a multicenter study. Schizophrenia Linkage Collaborative Group for Chromosomes 3, 6 and 8

In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = 0.001) and 2.68 (Combined sample, p = .0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p = .0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions