Toward a world consensus on prevention of schizophrenia

Screening for preschizophrenia in the general population with the aim of preventing transition to full-blown illness is an epidemiological impossibility because a rare disease cannot be predicted. The lack of specificity resulting in abundance of false-positives can be remedied in part by using much more restrictive screening criteria that combine several indicators of risk for transition to schizophrenia. Raising the specificity (reducing the false-positives), however, can only be done at the expense of sensitivity (increasing the false-negatives). The most commonly used strategy to raise specificity is the sample enrichment strategy. This involves the creation of samples enriched with schizophrenia risk by selectively filtering at-risk people out over a range of consecutive referral processes starting in the general population, through to general practioners, mental health services, and the early detection clinic. However, improvements in specificity obtained by the sample enrichment strategy should not be attributed to the use of some predictive instrument that supposedly identifies high-risk individuals. The epidemiologically and ethically most viable way for screening and early detection is to selectively increase the permeability of the filters on the pathway to mental health care. This will occasion samples of help-seekers enriched with schizophrenia risk at the level of mental health services (thus reducing false-positives), while at the same time making an attempt to "attract" as many detectable schizophrenia prodromes as possible through the filters along the pathway to mental health care (thus reducing false-negatives). Early psychosis research has yielded some useful suggestions in that it is becoming increasingly clear that it is not just psychosis itself, but rather the clinical context of the psychotic experience that determines risk for transition to schizophrenia. Thus, risk for transition to full-blown psychotic disorder is to a large degree determined by size of psychosis "load," comorbid distress and depression, cannabis use, cognitive ability, and subjective reports of impairment and coping. Making a diagnosis of psychotic disorder is not an exact science: it involves an arbitrary cutoff imposed on dimensional variation of psychopathology and need for care over time. Gaining insight into the cognitive and biological factors that drive the dimensional variation, including therapeutic interventions, is arguably more useful than sterile dichotomous prediction models.     

Life events and completed suicide in schizophrenia: a comparison of suicide victims with and without schizophrenia.

Adverse life events are an established risk factor in completed suicide. However, few studies have examined life events and suicide in schizophrenia. We investigated and compared schizophrenia suicide victims and age- and sex-matched victims without schizophrenia as part of a psychological autopsy study of all suicides in Finland over a 12-month period. Recent life events were examined retrospectively by interviewing next of kin using a structured life event questionnaire. Overall, nearly half (46%) the schizophrenia subjects had had adverse life events before suicide, significantly less than the nonschizophrenia subjects (83%). In both groups, however, suicide was preceded by life events independent of the victims' own behavior, such as death of a close person or illness in the family. Life events overall were more common among schizophrenia outpatients (52%) than inpatients (22%), and the association of life events with suicide was clearest among a subgroup of outpatients in residual phase who had used neuroleptic medication regularly. Overall, the prevalence of recent adverse life events varied between clinical subgroups of victims with schizophrenia, which may have implications for suicide prevention.     

Toward a new philosophy of care: Perspectives on prevention

The history of medical care in America and the present practice of mental health professionals generally reflect the economic structure of the country and of supply and demand. Revision is seriously needed in the areas of service delivery and training to give emphasis to primary prevention, and this requires social action on two levels: redirection of national priorities and development of a new philosophy of care founded in service and committed to prevention. Prevention is a form of response that can be made to existing and anticipated societal difficulties, to attempts to resolve them, and thus to planning properly for the future. Such plans must involve specific goals, purposes, attainable relevant programs, and the ability of providers and consumers to plan and act collaboratively; education of both providers and consumers: and making use of the political process to support this new philosophy of care both morally and financially. The tools of modern technology can be adapted and brought to bear on the problem of mental health care and mental illness prevention so that society can move beyond past failures to a system of care for the mentally ill that can keep pace with our complex modern society.     

Neuroinflammation in suicide: Toward a comprehensive model

Objectives. Suicidal behaviour (SB) entered the DSM-5, underlying a specific biological vulnerability. Then, recent findings suggested a possible role of the immune system in SB pathogenesis. The objective of this review is to present these main immune factors involved in SB pathogenesis. Methods. We conducted a review using Preferred Reporting Items for Systematic reviews and Meta-Analysis criteria, and combined (“Inflammation”) AND (“Suicidal ideation” OR “Suicidal attempt” OR “suicide”). Results. Post mortem studies demonstrated associations between suicide and inflammatory cytokines in the orbitofrontal cortex, a brain region involved in suicidal vulnerability. Also, microgliosis and monocyte–macrophage system activation may be a useful marker of suicide neurobiology. Kynurenine may influence inflammatory processes, and related molecular pathways may be involved in SB pathophysiology. Few recent studies associated inflammatory markers with suicidal vulnerability: serotonin dysfunction, impulsivity and childhood trauma. Interestingly, the perception of threat that leads suicidal individuals to contemplate suicide may activate biological stress responses, including inflammatory responses. Conclusions. Translational projects would be crucial to identify a specific marker in SB disorders, to investigate its clinical correlations, and the interaction between inflammatory cytokines and monoamine systems in SB. These researches might lead to new biomarkers and novel directions for therapeutic strategies.     

Awareness of disorder and suicide risk in the treatment of schizophrenia: results of the international suicide prevention trial

OBJECTIVE: Schizophrenia is characterized by high suicide risk and low awareness of disorder. Although awareness has benefits for medication compliance and clinical outcome, it is unclear how it may relate to suicide risk in this population. METHOD: This multicenter investigation assessed awareness and suicide-related behavior in 980 patients with schizophrenia or schizoaffective disorder. Patients were followed over 2 years and assessed by blinded raters for suicide-related events. RESULTS: Awareness of psychiatric condition at baseline was associated with increased risk of suicide events over the follow-up. This effect was mediated by depression and hopelessness levels. By contrast, changes in awareness associated with treatment decreased the risk of suicide. CONCLUSIONS: Although some patients may become depressed after acknowledging the clinical handicaps of their disorder, treatment-related changes in awareness are generally associated with a positive outcome relative to suicide risk. The complex interactions and mediation effects of these clinical variables require careful monitoring.     

A computer information system in a suicide prevention centre.

The process of planning and implementing a computer information system in a suicide attempt counselling service is described. The discussion highlights the importance of: involving line workers at all stages, clearly defining the uses the data will be put to, and establishing a forum for periodic reviews of the system. The hardware and software options we elected to choose are also described.     

Relapse prevention in schizophrenia - new therapeutic challenges

Schizophrenia is a chronic progressive illness characterized with frequent relapses and requiring long-term treatment. In spite of the fact that this disorder belongs among ten leading causes of disability worldwide, the consequences and difficulties associated with schizophrenia are frequently underestimated. The course of the illness is further characterized by a high percentage of suicides and attempted suicides, decline in cognitive functions and frequent relapses. The results of numerous studies indicate that early treatment with antipsychotics leads to better long-term outcomes compared with control groups. In the process of deciding about treatment we must bear in mind the importance of individual approach to schizophrenic patients because there are significant differences in the type of disorder, symptoms, co-morbidity, course of disorder (first episode or chronic course), as well as the differences in treatment response and treatment adherence. When choosing an antipsychotic agent we should try to find the drug capable of addressing all aspects of the illness that is safe and well tolerated in long-term treatment; we should start the treatment as early as possible, reduce the psychotic symptoms and avoid negative effects on functioning, whilst avoiding adverse effects and establishing a trusting and productive therapeutic alliance with the patient. Existing evidence strongly suggests the use of adequate doses of antipsychotics as early as in prodromal psychosis. Evidence shows that schizophrenic patients remain longer in treatment with atypical antipsychotics particularly when they are applied as depot injections, because the efficacy of treatment is higher, drug concentration stable and long-lasting, there are fewer adverse effects, and the co-operation with the service provider is better. In this way, the atypical antipsychotics provide us with the opportunity to establish long-term control of the psychotic symptoms, and reduce relapse rate and the number of hospitalizations while improving the quality of life of schizophrenic patients and establishing optimal therapeutic alliance.     

Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis

Background: People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor. Aim: Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide. Method: Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records. Results: Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters. Conclusion: Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.     

Toward a clarification of primary prevention

The ambiguity of the concept of primary prevention and a vague fear that primary prevention may violate civil liberties are two of the important barriers blocking the implementation of primary prevention. Progress toward overcoming these barriers may be possible by distinguishing between the different but overlapping meanings of primary prevention. In this paper four models of primary prevention are proposed to aid definitional accuracy and to help identify and avoid those types of preventive interventions which threaten civil liberties.     

Toward a modern search for schizophrenia genes

Genetic epidemiology has provided consistent evidence that schizophrenia has a genetic component It is now clear that this genetic component is complex and polygenic, with several genes interacting in epistasis. Although molecular studies have failed to identify any DNA variant that clearly contributes to vulnerability to schizophrenia, several regions have been implicated by linkage studies. To overcome the difficulties in the search for schizophrenia genes, it is necessary (i) to use methods of analysis that are appropriate for complex multifactorial disorders; (ii) to gather large enough clinical samples; and (iii) in the absence of genetic validity of the diagnostic classification currently used, to apply new strategies in order to better define the affected phenotypes. For this purpose, we describe here two strategies: (i) the candidate symptom approach, which concerns affected subjects and uses proband characteristics as the affected phenotype, such as age at onset, severity, and negative/positive symptoms; and (ii) the endophenotypic approach, which concerns unaffected relatives and has already provided positive findings with phenotypes, such as P50 inhibitory gating or eye-movement dysfunctions.     

The lifetime risk of suicide in schizophrenia: a reexamination

BACKGROUND: The psychiatry literature routinely quotes a lifetime schizophrenia suicide prevalence of 10% based on 1 meta-analysis and 2 studies of chronic schizophrenics. OBJECTIVES: To build a methodology for extrapolating lifetime suicide prevalence estimates from published cohorts and to apply this approach to studies that meet inclusion criteria. DATA SOURCES: We began with a MEDLINE search (1966-present) for articles that observed cohorts of schizophrenic patients. Exhaustive bibliography searching of each identified article brought the total number of articles reviewed to 632. STUDY SELECTION: Studies included in the meta-analysis observed a cohort of schizophrenic patients for at least 2 years, with at least 90% follow-up, and reported suicides. Articles are excluded for systematic age bias (ie, adolescents). DATA EXTRACTION: Extracted data included sample size, number of deaths, number of suicides, percentage of follow-up, and diagnostic system used. Data were extracted independently by 2 of us, and differences were resolved by consensus after re-review. DATA SYNTHESIS: Studies were divided into 2 groups: 32 studies of schizophrenics enrolled at various illness points (25 578 subjects) and 29 studies of schizophrenics identified at either illness onset or first admission (22 598 subjects). Regression models of the intersection of proportionate mortality (the percentage of the dead who died by suicide) and case fatality (the percentage of the total sample who died by suicide) were used to calculate suicide risk in each group. The estimate of lifetime suicide prevalence in those observed from first admission or illness onset was 5.6% (95% confidence interval, 3.7%-8.5%). Mixed samples showed a rate of 1.8% (95% confidence interval, 1.4%-2.3%). Case fatality rates showed no significant differences when studies of patients diagnosed with the use of newer systems were compared with studies of patients diagnosed under older criteria. CONCLUSION: This study estimates that 4.9% of schizophrenics will commit suicide during their lifetimes, usually near illness onset.     

Attempted suicide and depression in schizophrenia

The relationships between symptoms and both prior suicide attempts and current suicidal thinking were examined in a sample of schizophrenics at 2 points in time. Fifty subjects meeting DSM-III criteria for schizophrenia were assessed within 1 week of admission, and 41 were reassessed at a 6-month follow-up. On admission, prior suicide attempts were significantly associated with current depression, female sex, lower education and more frequent hospitalization. The association with depression remained significant at follow-up. In addition, current suicidal thinking was associated with depression at both times but also with negative symptoms at time 1 and delusions and hallucinations at time 2. These findings confirm and strengthen prior reports of an association between depression and attempted suicide.     

Lithium: poisonings and suicide prevention.

This study concerns 81 cases of lithium poisoning and shows that deliberate intoxications are prevalent during the first 3 years of lithium treatment as well as in cases with a previous history of suicide attempt. Therapeutic intoxications could generally be avoided by education concerning hygiene and diet and careful monitoring in cases of intercurrent diseases.     

Learning from outcome studies. Toward a comprehensive biological-psychosocial understanding of schizophrenia

According to results from three major European long-term outcome studies on schizophrenia, from other comparable studies, and from additional investigations on rehabilitation and on the influence of psychosocial factors, long-term evolution of schizophrenia is much more variable and considerably better than hitherto admitted. On this basis, the author presents a comprehensive biological-psychosocial evolutionary model of schizophrenia in three phases, centered around the vulnerability- and information-processing hypotheses. Long-term evolution of schizophrenia cannot be sufficiently represented by a linear organic process mainly determined by genetic factors. Environmental and, in particular, psychosocial factors, also seem to play an important role. Vicious biological-psychosocial circles with multiple feedback effects can lead to non-linear escalating processes. Chronic states appear to be the result of complex interactions between preexisting vulnerability and autoprotective counterregulations on a biological, psychological and social level. Some therapeutic consequences and possible future developments of these concepts are presented.