From Prevention to Preemption: A Paradigm Shift in Psychiatry

Universal prevention has been a focus of psychiatric research for the past 4 decades. Using a public health approach, research has shown that mitigating major risk factors, such as poverty and early life stress, and promoting protective factors can improve behavioral outcomes. In other areas of medicine, we have observed how similar preventive approaches have reduced deaths from cancer and infectious disease. By contrast, while reducing environmental stress and providing better maternal support improve general behavioral outcomes (by preventing the development of antisocial behavior, for example), there are few, if any, examples of preventive approaches in psychiatry that reduce either the morbidity or the mortality of our most disabling illnesses-such as schizophrenia and bipolar disorder.^1,2

What can be done to improve the impact of preventive interventions in psychiatry? Do we have effective preventions that are not being implemented? Or do we need new approaches
to reduce morbidity and mortality? While we certainly can do much more to implement what we already know, it may soon be time for us to consider a shift from universal prevention provided in the broad population to “preemptive” approaches. Preemptive interventions target those at greatest risk for mental illness and those with subdiagnostic signs or symptoms, and they provide what previously has been labeled “selective” and “indicated” prevention.³

This preemptive approach in medicine is emerging as the focus of health care shifts from acute to chronic disorders. Until recently, our approach to most medical disorders was based on the infectious diseases of the 20th century, acute illnesses with a rapid onset that could be prevented by such universal approaches as vaccination and vector eradication. This model may not suffice for the chronic diseases, which will be the preoccupation of health care in the 21st century. While eliminating general risk factors, such as smoking and obesity, remains a goal in the prevention of chronic diseases, increasingly we recognize the need to identify individual patterns of risk so that preemptive interventions can be directed to those at greatest risk.

A trajectory model will be critical, recognizing that chronic disorders evolve for years or even decades before they are diagnosed in their late stages (for example, dementia or psychosis). Atherosclerosis is an instructive example: a disease that used to be diagnosed in its end stage as myocardial infarction is now diagnosed years earlier based on a range of individual risk factors (family history, plasma lipid levels, electrophysiology, and imaging results) and treated with diet, exercise, and medication to preempt ischemic damage.

Virtually all mental disorders are chronic disorders. Moreover, the National Comorbidity Survey Replication further demonstrated that mental disorders are the chronic disorders of youth.⁴ Could we approach schizophrenia, mood disorders, and anxiety disorders with preemptive strategies? The answer requires 2 kinds of progress:

• Understanding patterns of risk that predict disorder for an individual.
• Developing effective interventions for preemption.

How far are we from these 2 goals for mental disorders?

We do not have biomarkers for early detection of any mental disorder. We do, however, know a number of risk factors for each of the common mental disorders. Depending on the disorder, family history, childhood history, and previous psychopathology are significant predictors.

A few examples may help illustrate this point. Children who have been severely abused physically or sexually have more than twice the risk of developing major depressive disorder.⁵ Those who have made a suicide attempt are at a 40-fold increased risk of dying from suicide.⁶ And as many as 80% of adolescents in whom a psychotic disorder will eventually develop can be identified when the disease is in the prodromal stage-before the onset of psychosis-on the basis of subacute clinical symptoms, family history, and dramatic changes in social functioning.⁷ Genetics will likely provide a new generation of factors that will be added to the assessment of risk. As with heart disease and cancer, it is likely that individual risk for any specific mental disorder will be determined by a combination of factors, rather than by a single biomarker. One can imagine a time in the not-too-distant future when a 15-year-old with a family history of schizophrenia or bipolar disorder could be assessed with cognitive, genetic, and imaging tests to diagnose the early stages of schizophrenia or bipolar disorder well before a psychotic episode.

Of course, the question remains, if we could predict schizophrenia, what would we do about it? Should every adolescent “at risk” be treated with antipsychotic medications? What is the evidence that medications forestall or preempt psychosis? If effective, how long would one administer the treatment? And even if predictors are 90% accurate (a high bar), what about the 10% of false-positive results that would lead to unnecessary treatment? All treated patients would be exposed to possible adverse effects of medication.

These questions and many others point out the need for re-thinking interventions in psychiatry-a process that has been under way for some time in other areas of medicine and is now receiving attention in psychiatry.⁸ Three current opportunities may be illustrative. The recent evidence of cognitive deficits in adolescents with schizophrenia years before the first psychotic episode suggests the importance of developing cognitive interventions to preempt the later phases of this illness.^9,10 Recent information technology approaches to cognitive remediation suggest the potential of using the brain’s inherent plasticity to alter circuitry and functioning without medication.¹¹

As a second example, posttraumatic stress disorder (PTSD) responds to cognitive-behavioral therapy (CBT). Early data suggest that CBT following a traumatic event can reduce the incidence of PTSD in those at greatest risk.¹² Third, data from several studies support the efficacy of lithium for reducing the number of suicides in those with mood disorders. In a meta-analysis of 32 trials, persons treated with lithium showed a 74% reduced risk of death from suicide.¹³

This shift in paradigm not only alters our approach to prevention, it also redefines mental disorders. Currently, mental disorders are diagnosed by late-stage symptoms, such as psychosis. If mental disorders are viewed as chronic illnesses with developmental onset, then we should be able to detect subtle, diagnostic changes in brain and behavioral functioning many years before the most disabling symptoms emerge. This suggests a shift in the definitions of schizophrenia and bipolar disorder that is similar to the change from myocardial infarction to atherosclerotic cardiovascular disease, which links diagnosis to pathophysiology and associated risk factors rather than to symptoms. Moreover, current psychiatric medications, when they are “effective,” are usually palliative and only reduce symptoms. A preemptive approach promises to reduce morbidity and mortality by intervening early, before the full syndrome develops, and re-aligning the trajectory of development so the individual identified as at risk has the greatest opportunity for the best outcome. In this sense, psychiatry can follow the path taken by oncology and cardiology.

What can we expect in the next decade? Is preemption feasible in this time frame? Recent breakthroughs in genomic and imaging technologies may well revolutionize psychiatric diagnosis by adding key elements and techniques for identifying patterns of risk that are amenable to early detection. Defining the genomic risk architecture of these disorders will require much larger studies than any published to date. Similarly, we will probably need more longitudinal, intrasubject studies to identify neural correlates of schizophrenia, mood disorders, and autism. However, there is every indication, from the use of these techniques in other areas of medicine, that we will be defining patterns of individual risk for mental disorders within the next few years in research settings, if not the community clinic.

In the meantime, there is much we can do with known predictors and proven intervention strategies that are in need of broader implementation in the community. We know already that a history of psychosis predicts a subsequent psychotic episode and that a suicide attempt is the highest risk factor fora subsequent completed suicide. Yet, more than 30% of those with a first psychotic episode will discontinue treatment in the first year, increasing their risk of relapse 5-fold, and fewer than 50% of adolescents presenting to emergency departments after a suicide attempt receive any follow-up.^14-16 Surely, we can do better. While research develops transformative information and tools for preemption, we need more effective implementation of currently available treatments to ensure the best outcomes. In the near-term, preventing relapse will have the greatest impact on public health.

References:

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