5 Jul 2015
As part of our ongoing coverage of the 2015 International Congress on Schizophrenia Research (ICOSR), held March 29 through April 1 in Colorado Springs, we bring you session summaries from some of the participants in the Young Investigator program. We are, as always, grateful for the gracious assistance of conference directors Carol Tamminga and Chuck Schulz, as well as meeting staff Cristan Tamminga and Dorothy Denton. For this report, we thank Danielle R. Jahn of the VA Maryland Healthcare System in Baltimore.
July 6, 2015. Suicide rates in schizophrenia are high, with a lifetime risk of death by suicide estimated at approximately 5 percent (Palmer et al., 2005). However, suicide remains understudied in people with schizophrenia, and suicide risk is not well understood. The March 30 morning session at the ICOSR titled "A new perspective on the problem of suicide and schizophrenia: ideation, epidemiology, epigenetics, and intervention," sought to bring together different perspectives on suicide risk to provide new and helpful information to researchers and clinicians who work with this high-risk population. Presentations focused on identifying patterns in relationships between suicide ideation and later death by suicide, predicting suicide in schizophrenia, genetic and epigenetic influences on risk for suicide attempts, and lessons from designing and implementing a suicide prevention trial.
Michael Davidson of Chaim Sheba Medical Center in Israel, the chair of the session, opened by discussing current views of suicide risk and assessment. He noted that practitioners may focus too much time on preventing rare events, such as suicide, which are not predictable and may not be preventable. He also discussed the need for research and clinical practice to focus on imminent risk. Prediction of eventual death by suicide is not enough; clinicians also need to know when someone will be at highest risk. Davidson also noted that "common sense" may not actually work in suicide prevention. For example, he shared that evidence shows that no suicide contracts are "completely useless," denial of suicide ideation may not be associated with lower risk, and involuntary hospitalization may not decrease suicide risk. However, removing firearms or means restriction appears to be helpful. Davidson then introduced the first presenter.
The first presentation in the session was given by Matthew Large of the University of New South Wales in Sydney, Australia, who discussed the differences in the strength of the relationship between suicide ideation and later death by suicide across schizophrenia spectrum disorders and mood disorders. The study was published recently in Acta Psychiatrica Scandinavica (Chapman et al., 2015) and was inspired by previous work that has found a relatively weak association between suicide ideation and death by suicide in psychiatric inpatients (weaker even than the association between gender and death by suicide in the general population). Large questioned whether this weak association may mask differences based on various psychiatric diagnoses. He found that the odds ratio was over four times higher in schizophrenia spectrum disorders than in mood disorders, indicating clear differences between these psychiatric diagnoses. Large's talk concluded with a number of possible explanations for this finding. The chronic nature of schizophrenia (vs. episodic natures of mood disorders) may explain the stronger effect, or theory of mind may be better in those with mood disorders, so they know not to report suicide ideation if they want to be discharged. Large indicated that it is important to note that suicide ideation seems to be indicative of long-term, not imminent, suicide risk, and concluded that even if it is not a strong predictor of death by suicide in all groups, suicide ideation should be assessed because it indicates a patient's distressed internal state.
Next, Mark Weiser of Tel Aviv University in Israel gave a presentation titled, "Suicide in schizophrenia: can we predict it?" He focused on two studies in his presentation. First, in a large sample of Israeli men, high IQ in men with schizophrenia prior to illness onset was strongly associated with death by suicide during an average follow-up of 10 years, whereas low IQ was associated with death by suicide in the general population. This led Weiser to emphasize a take-home message of the need for clinicians to be aware of suicide risk in people with schizophrenia who are bright or were high functioning in school prior to illness onset. Weiser and colleagues also examined the timing of death by suicide in this population and found that nearly one-third of suicides occurred during hospitalization, and nearly half occurred within one month of hospitalization. These data suggest the need to be critically aware of suicide risk in the time surrounding psychiatric hospitalization. However, Weiser also noted that the vast majority of people with schizophrenia do not die by suicide, and we cannot predict suicide.
Weiser presented data from a 25-year study of inpatient suicides, which found 1,340 admissions per suicide yearly. He then posed a question to the audience: given the significant decrease in the number of available beds, decrease in the average length of stay, and increase in the number of admissions over the past few decades, how should suicide rates be affected over time? There are two possibilities: these changes could mean that only more severe patients are admitted, suggesting higher rates of inpatient suicide, or they could mean there is less time overall in inpatient settings, suggesting lower rates of inpatient suicide. The data indicate that the latter is accurate, as inpatient suicide rates have decreased over time. Additionally, the decreases in national suicide rates do not fully explain the decreases in inpatient suicide rates. Weiser provided another conclusion based on these data: that psychiatric hospitalization does not prevent suicide. He closed by re-emphasizing that it is impossible to predict suicide, even while on psychiatric inpatient units.
The third presentation was focused on genetic and epigenetic influences, and was given by Vincenzo De Luca of the University of Toronto in Canada. De Luca began by discussing the evidence for the assertion that suicide runs in families (e.g., Egeland and Sussex, 1985) and noted that family, twin, and adoption studies provide evidence that genetics plays a role. He also explained the types of genetic studies that have been undertaken, including candidate gene studies that have focused on the 5HT gene and GWAS that are not specific to one hypothesized gene, and he emphasized the importance of genetic studies to develop neurobiologically targeted treatments to reduce suicide risk.
De Luca also discussed methylation and CpG SNPs, which may also be important based on recent studies (Guintivano et al., 2014). De Luca's study focused on 80 participants with schizophrenia or schizoaffective disorders, 38 of whom had attempted suicide. He examined both CpG SNPs in a GWAS and found some promising trends, though none of the SNPs were statistically significant. De Luca emphasized the promise of these techniques and noted that the small sample size collected thus far may limit the findings presented.
Ravi Anand of Newron Pharmaceuticals, headquartered in Milan, Italy, concluded the session by discussing considerations in the design of trials to reduce suicide risk. He talked about the well-known InterSePT study (Meltzer et al., 2003), some design considerations of which have been reviewed in a published paper (Alphs et al., 2004). InterSePT was the first pharmaceutical trial focused specifically on reducing suicide risk. In his presentation, Anand highlighted the importance of designing suicide-focused trials as pragmatic rather than explanatory. In line with this design, InterSePT was an open-label pragmatic trial, which ultimately worked well. Other challenges included defining the population of interest, selection criteria, outcomes, assessment instruments, comparator, blinding, and sample size. He also emphasized the need for government agencies, researchers in academia, and sponsors/industry to work together to thoughtfully design such trials and ensure they are implemented effectively. Anand highlighted that even though the study was complex, enthusiasm from investigators was high, the enrollment rate was good, and dropout was relatively low. He also noted that the increased contact involved in this trial may have been one of the keys to the relatively low suicide risk observed across groups and that patients who had attempted suicide within a year and were early in the course of schizophrenia are probably most at risk and thus most in need of care. The lessons learned from the InterSePT trial may be beneficial to investigators designing suicide-focused trials in the future.—Danielle R. Jahn.