Early Detection and Intervention in Schizophrenia

Chairperson: Jeffrey Lieberman, MD

In recent years the prospect of early detection and intervention to forestall the onset or limit the morbidity and disability associated with schizophrenia has taken hold and generated great enthusiasm. Although much remains to be done to develop the methodology and evidence for effective intervention strategies, initial results of studies show considerable promise for this strategy. This symposium focused on presenting the most recent results of key projects that have been conducted to evaluate the effects of early detection/intervention strategies. Each speaker commented on work in their particular area of interest and presented the results of their most current studies.

Early Interventions in Psychiatry: Lessons from Psychosis

Patrick McGorry, MD, PhD

Mental and substance use disorders are the key health issue for emerging adults, which if persistent, may constrain, distress and disable for decades. Epidemiological data indicate that 75% of people with mental disorders have an age of onset by 24 years of age, with new onsets peaking in the early twenties. In recent years, a worldwide focus on the early stages of psychotic disorders has improved understanding of these complex disorders and their outcomes. This reform paradigm has also illustrated how a staging model may assist in interpreting biological data and refining diagnosis and treatment selection. We now have a strong evidence base supporting early intervention in psychosis including robust cost effectiveness data and growing evidence that intervention even prior to full expression of the psychosis phenotype is feasible and effective. This paradigm can now be extended to mood and other major mental disorders. Furthermore the critical developmental needs of emerging adults are poorly met by existing service models. Young people need a different culture of service provision to engage with and benefit from interventions. The need for structural reform and a new research agenda is clear.

Why Treating Early, Treating Well, and Treating for Life Is Important in Schizophrenia

Rene Kahn, MD, PhD

Studies emphasizing functional decline in schizophrenia as a clue to its pathogenesis, suggest that brain abnormalities in schizophrenia could be expected to reflect this clinical progression. We, and others, have reported brain abnormalities to increase over time in schizophrenia. Interestingly, not all patients show changes in brain volumes over time: we demonstrated that the changes are particularly pronounced in those patients with a poor prognosis in the first years of illness. Moreover progressive changes are most pronounced in the frontal and temporal areas as postulated by Kraepelin over a hundred years ago. We found that brain loss over time was most pronounced in patients who had been psychotic longest. Finally, the progression in these frontal brain changes appeared to be attenuated by treatment with atypical, but not by typical antipsychotics. Thus, not only are brain changes progressive in schizophrenia, they are clinically relevant since they are related to outcome and may be reversed by some of the atypical antipsychotics. With the evidence pointing to a link between progressive disease and patient outcomes, it is becoming increasingly clear that every effort should be made to prevent psychotic relapses. Using medications with maximal effect is therefore warranted.

Selective and Indicated Prevention for Schizophrenia: An NIMH Perspective on Current and Future Possibilities

Robert Heinssen, PhD

The National Institute of Mental Health Strategic Plan callsfor research to chart the course of mental disorders overthe lifespan in order to understand stages of risk as well asopportunities and methods for preemptive intervention.Two current NIMH-funded research initiatives in earlyphase schizophrenia illustrate complementary strategiesfor achieving risk prediction and preemption goals. TheNorth American Prodrome Longitudinal Study (NAPLS)explores clinical high-risk states that precede the onsetof psychosis using genetic, neurobiological, cognitiveneuroscience, and behavioral research methods. NAPLS’goal is to identify robust and malleable risk factors forpsychosis onset, and then to develop and pilot innovativerisk reduction strategies. Recovery After an InitialSchizophrenia Episode initiative (RAISE) tests approachesfor treating first episode psychosis within the context of theU.S.health system, using evidence-based interventions thatcan be implemented on a population-level basis. RAISEemphasizes multimodal treatment packages to be deliveredin community settings by well-integrated treatment teamswithin a recovery-oriented, personalized framework. Earlyfindings from these two initiatives were discussed inrelation to the NIMH Strategic Plan, particularly the goalof developing targeted, impactful interventions that willalter the course of schizophrenia.

PortlandIdentification and Early Referral (PIER): Prevention of Psychosis as a Public Health Intervention

William McFarlane, MD

Portland Identification and Early Referral (PIER) is a population-based system for early detection and treatment for the prodrome to psychosis in people ages 12-35. PIER educated the community-at-large and trained over 7300 health, education and youth-related professionals to identify young people at high risk of psychosis. Eligibility was established by the SIPS criteria. Treated cases received a comprehensive, evidence-based and prodrome-specific combination of psychoeducational multifamily group, supported education/employment, assertive community treatment and psychotropic medication. Outcome measures were first episodes of psychosis and changes in GAF during one year of intervention, and differences in clinical incidence rates (first hospitalizations for a psychosis) in experimental vs. control catchment areas before (1994-2000) vs. during (2001-2007) the intervention study. Over seven years, there were 780 referrals, of which 274 (35%) were assessed and 148 (19%) were admitted to study. 13 (9%) experienced >30 days of psychosis during one year of treatment. Mean GAF was 38.3 at baseline and 56.4 at 12 months (pre-post, p<0.01). The net pre-post difference in clinical incidence between control and experimental areas was 22.8/100,000 (ARIMA, p<0.0001). The relative difference in incidence between treatment and control areas is consistent with a community-wide prevention effect, simultaneously confirming accuracy of identification and preventive effect for treatment.

At Clinical High Risk for Psychosis — What Is the Outcome?

Jean Addington, PhD

There has been increasing interest in early detection during the prodromal phase of a psychotic disorder. A major focus is on determining the risk of conversion to psychosis and on developing algorithms of prediction. To date a few treatment studies have been published with some promising results for both pharmacological treatments using second-generation antipsychotics and psychological interventions mainly with a focus on cognitive behavioral therapy (CBT). This talk presented data from a treatment trial of CBT versus supportive therapy for individuals at clinical high risk of developing psychosis. In this study, conversions to psychosis only occurred in the group who received supportive therapy. Although this is an important result it is necessary to review subsequent changes in comorbid diagnoses, symptoms and functioning to better understand the outcome of those who are seen to be at clinical high risk beyond the outcome of conversion to psychosis. Further results from our studies with this clinical high-risk group demonstrate that although improvements in clinical symptoms are often observed, improvements in functioning are much less frequent. These results have implications for early detection and intervention in the pre-psychotic phase and for designing future treatments.

Early Detection and Intervention in Psychotic Disorders: Making it Ready for Prime Time

Jeffrey Lieberman, MD

This presentation described studies attempting to develop biological measures to aid in the diagnosis of patients in the prodromol phase or who are at high risk for developing schizophrenia or related psychotic disorders. Specifically, Lieberman reviewed the limitations of current diagnostic approaches and the problem with false positive case identification. Then he described the most promising ongoing lines of investigation using neuroimaging methodology including functional MRI and PET scanning to access pathophysiological processes indicative of an incipient psychotic disorder. Finally, therapeutic strategies that may be tested in the context of an identified at-risk patient population were considered. The rationale and goals of the ongoing NIMH funded

RAISE project (Recovery After an Initial Schizophrenia Episode) was presented in this context.

Adapted from materials found on the American Psychiatric Association Annual Meeting website.