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Research Directions

Research into the first episode of psychosis continues to expand, which will help to better inform service and treatment options for individuals, advocates and policymakers alike. It is important to note that different study designs in key areas of research are targeting different populations or stages in the development of an illness process and may be measuring outcomes and processes differently. Many of these studies are international in origin, and it is exciting to see how many different research groups are approaching the best ways to address people in the first episode of psychosis.

For example, the first episode of psychosis does sometime lead to an extended period of psychosis, and there are some relevant research studies from that outcome woven into this research summary—they will usually be framed as early schizophrenia.

An example of this variance in research focus can be seen by looking at a sample of recent initiatives. One is the national Recovery After Initial Schizophrenia Episode (RAISE) trial, which presumes a diagnosis of schizophrenia and looks to better understand the components that improve recovery in early stages of that illness. The Viennese fish oil study is more preventive in design, aiming to identify individuals at risk in order to prevent the development of psychosis. Marijuana research aims to target risk correlations in the development of psychosis, and to genetic variations that may raise an individual’s risk that uses marijuana. And finally, some creative and comprehensive approaches have been studied in different cultures (e.g. Open Dialogues in Western Lapland, China combination treatment and CBT in Melbourne, Australia) yet their applicability to a diverse U.S. population and culture has yet to be investigated.

Research is always being updated and developed to better understand key issues in this important field, and resources to follow this research are noted at the conclusion of this section.

RAISE: A National U.S. Clinical Trial

Recovery after an Initial Schizophrenia Episode is a National Institute of Mental Health (NIMH) funded research project. The goal of the NIMH-funded trial is to “fundamentally change the trajectory and prognosis of schizophrenia through coordinated and aggressive treatment in the earliest stages of the illness.” The study is led by John Kane, M.D. of the Feinstein Institute for Medical Research in Manhasset, N.Y., and Susan Essock, M.D., at Columbia University in New York City. There are 35 centers across the country, found in 21 states, participating in the early treatment component of the trial led by Dr. Kane. Residents of New York and Maryland may be eligible for Dr. Essock’s arm of the study. If, when contacting a local center, the trial is full or completed, ask to speak with one of the investigators of the study at your nearest local site. They may know of another investigational effort you could participate in and may know where to get the best care in your area. Results from this compelling effort will continue to emerge in the medical literature in the coming years.

For information or to learn more about enrollment, visit the RAISE website.

NAMI Commentary: RAISE represents an important effort to use scarce NIMH resources earlier in the course of schizophrenia and to improve care and course for individuals living with this illness. Many investigational sites across the national in community settings make this accessible. Follow the literature or NAMI resources to see research that comes from this promising trial.

Fish Oil and Prevention of Progression to Psychosis

G. Paul Amminger, M.D., and his colleagues investigated the use of marine fish oil as a possible preventative agent in teens and young adults at risk for psychosis in Vienna, Austria. The study randomized 81 young people aged 13-25 who had shown some early signs of psychosis into two groups, one that received fish oil and one that received a placebo (coconut oil), each for three months. The groups also received some psychosocial interventions. After one year, 4.9 percent of the fish oil treated group progressed to psychosis while 27.5 percent progressed to psychosis in the placebo group

Amminger P., Schafer, M. et al., “Long Chain Omega-3 Fatty Acids for Indicated Prevention of Psychotic Disorders,” Archives General Psychiatry Vol 67, (No 2), Feb. 2010.

NAMI commentary: This study was small, (N:81 subjects) and needs to be replicated. Yet given the tolerability and lack of downsides to an accepted dietary intervention, use of fish oil has become a common practice in approaches to this population, even as it is being researched further. None of the individuals in the study were taking antipsychotic medications, but some took antidepressant medications, which could potentially confound the results. All subjects received nine sessions of psychological or psychosocial intervention so those interventions alone were not the “active ingredient” in the improvement in the fish oil group. This study used a randomized controlled trial design, which is the gold standard of medical research, in order to reduce selection bias, chance and other factors to account for the intervention’s impact. This could be a groundbreaking preventive study if replicated in a larger and more diverse population.

Medications with Psychosocial Intervention

In China, a randomized controlled trial led by Guo compared 1268 individuals with early-stage schizophrenia, comparing antipsychotic medications alone to antipsychotic medication plus 12 months of “psychosocial intervention consisting of psychoeducation, family intervention skills-training and cognitive behavior therapy administered during 48 group sessions.” The authors conclude that the combination group “showed lower rate of treatment discontinuation or change, lower risk of relapse and improved insight, quality of life and social functioning” and also had better work and school outcomes.

Guo et al., “Effect of Antipsychotic Medication Alone versus Combined with Psychosocial Intervention on Outcomes of Early Stage Schizophrenia,” Archives of General Psychiatry 2010: 67 (9) 895-904.

NAMI Commentary: This is a large, randomized trial that demonstrates better outcomes for individuals with early stage schizophrenia who were randomized to combined medication and psychosocial treatments. Not all individuals with first episode psychosis develop schizophrenia, but this is a compelling study for those who do progress to schizophrenia. Essential outcomes like work, school and quality of life all improved in the treatment group. The comprehensive, 48-week psychosocial intervention design may be hard to replicate in community clinics and many people reports challenges in finding cognitive behavior therapy in the U.S. How culture impacts this service equation in China is not clear, but these results have echoes in American literature, which makes intuitive sense given the literature supporting both interventions independently.

Medication Free Research in Early Episode

Bola reviewed the literature on the “question of whether short periods of medication free research in early episode schizophrenia result in demonstrably long term harm to human subjects.” There were only six studies that attempted to address this issue following subjects along for one year. He concludes, “Good quality evidence is inadequate to support a conclusion of long term harm resulting form short term postponement of medication in early episode research.”

Bola, “Medication Free Research in Early Episode Schizophrenia: Evidence of Long Term Harm?” Schizophrenia Bulletin Vol. 32, No. 2, 2006.

NAMI Commentary: This review demonstrates just how little we know as a field about long-term follow up and interventions for the treatment of first episode psychosis. Only six studies met even a one-year duration follow up, and these studies were comparing first generation antipsychotics to placebo, which limits the conclusions of the results. Some of the studies reviewed had major data gaps as well. This review teaches us primarily that we have a great deal more to learn in this important area.

Early Psychosis, Brain Changes and Medications: A Conflicting Literature

Two studies are noteworthy in this area.

Lieberman and colleagues conducted a study of 263 first episode individuals with schizophrenia in 14 sites in the U.S. and Europe, and randomized the population to either first-generation antipsychotic haloperidol or Zyprexa (olanzapine). The randomized, controlled trial showed grey matter brain loss in the haloperidol group but not in the olanzapine group. The group treated with haloperidol showed grey matter loss of about 2 percent. (Lieberman et al., American Journal of Psychiatry, 2005).

However, a different study of 211 subjects living with schizophrenia “soon after illness onset” found contradictory results. Ho and Andreason looked at these schizophrenia subjects early in treatment, followed them over seven to 14 years and concluded that “antipsychotics have a subtle but measureable influence on brain tissue loss over time, suggesting the careful risk benefit review of dosage and duration of treatment.” (Archives of General Psychiatry Vol. 68. no. 2 Feb. 2011.)

Lieberman et al, "Antispychotic Drug Effects on Brain Morphology in First Episode Psychosis" Archives General Psychiatry 2005; 62, April 2005.

NAMI Commentary: We have a great deal more to learn about the impact of antipsychotic medications on the brain. If medicines are useful for shorter-term symptom reduction but contribute to even subtle long term brain loss, that complicates the risk-benefit equation for the individuals who would be taking the medicines. David Lewis, M.D., who wrote an editorial for the Ho article, states that one explanation is that “antipsychotics improve symptoms and contribute to progressive brain tissue reduction through different actions in separate brain circuits.” He concluded, “The finding of Ho and colleagues should not be construed as an indication for discontinuing use of antipsychotic medications as treatment for schizophrenia. But they do highlight the need to closely monitor the benefits and adverse effects of these medications in individual patients to prescribe the minimal amount needed to achieve the therapeutic goal and to consider the addition of non pharmacologic approaches that may improve outcomes.” This latter study also illustrates the profound need for better-funded brain research at the basic science level as well as a need for a third generation of therapies for psychosis. (David Lewis, “Antipsychotic Medications and Brain Volume Do We Have Cause for Concern?” Archives General Psychiatry 2011. 68 (2).)

Childhood Psychotic Symptoms

Polanczyk and his colleagues followed 2232 children who presented with psychosis at age 5 over 7 years in order to better understand the presentation of psychosis and how it relates to schizophrenia. They found key risk factors for early onset psychosis including “heritable risks…and urbanicity, cognitive impairments at age 5, home-rearing risk factors, behavioral emotional and educational problems at age 5 and co-morbid conditions including self harm.” They conclude that “Psychotic symptoms in childhood are often a marker of impaired developmental processes and should be actively assessed.”

Polanczyk et al., “Etiological and Clinical Features of Childhood Psychotic Symptoms,” Archives of General Psychiatry 2010, 67 (4).

NAMI Commentary: We do not know enough about very early in life onset of psychosis, and the hope is that understanding it will help unlock clues about the presentation of psychosis including schizophrenia in young adult life. This study is part of the puzzle to help us understand the phenomenon. By following 2232 children for seven years who had self report of psychotic symptoms at age five, the research team did something remarkable as longitudinal research is as rare as it needed. As these children reach teen and young adult years, more will be learned to relate their course to that of more typical psychosis age of onset in the teens and 20s.

Marijuana and Earlier Onset of Psychosis

A systematic review of scientific research in first episode psychosis and cannabis use was done by a team of researchers led by Large. They identified 83 studies, in English, that addressed the relationship of cannabis and possible earlier onset of psychosis. Studies that also involved alcohol were included in the review, but the conclusions related to marijuana use. The authors conclude, “The results of the meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychosis, and they support the hypothesis that cannabis plays a causal in the development in some patients.”

Large, et al., “Cannabis Use and Earlier Onset of Psychosis: A Systematic Metanalysis,” Archives of General Psychiatry 2011, 68 (6).

NAMI Commentary: This is a comprehensive review of this important public health and risk topic. In sum, marijuana adds risk to vulnerable individuals, but unfortunately we do not have the tools to know precisely who is at risk. Earlier use of cannabis raises risks further. Marijuana is a hallucinogenic substance so this conclusion makes intuitive sense, but one many may not fully grasp. Due to the naturalistic nature of the studies we do not know that, if the users abstained, whether they would have developed psychosis later. The studies showed that cannabis users developed psychosis 2.7 years earlier than non-users. No relationship to earlier onset of psychosis was noted for alcohol use among teens and young adults. Counseling marijuana avoidance, providing support to reduce intensity of use and substance abuse programming is a sensible and preventive strategy that should be widely adopted.

Course of Substance Abuse in First Episode Psychosis

A review of the published literature was done by Wisdom and her colleagues. They found that one-half of the individuals with first episode of psychosis became abstinent or significantly reduced their alcohol and drug use after a first episode of psychosis. They conclude, “Experience education treatment or other factors led many to curtail their substance use disorders after a first episode of psychosis.”

Wisdom, J., Manuel, J., and Drake, R., “Substance Abuse Disorder Among People With First Episode Psychosis A Systematic Review of Course and Treatment,” Psychiatric Services 62, Sept. 2011.

NAMI Commentary: Understanding the relationship between substance use and the first episode of psychosis is important and this review fills an important need. How the individuals view substances over time remains an important element in their understanding of the two conditions. The health care field and policy makers need to better define what type of programming makes a difference for the dual diagnosis population as different cultures, funding structures and approaches often complicate integrated service efforts. This literature and research is particularly lacking in young adult population, which is of primary interest to the first episode population.

Trauma and Psychosis

Adverse or traumatic experiences have a relationship with many adult health concerns, both physical and psychiatric. The observation that many individuals who have presented with psychosis have been exposed to adverse experiences was recently reviewed looking at large survey data sets in the U.S. and England. Shevlin and his colleagues correlated the surveys finding and found a correlation with multiple adverse experiences and the later development of psychosis. They outline a clear, dose-dependent relationship between adverse experiences and the risk of later developing psychosis.

Shevlin et al, “Cumulative Traumas and Psychosis: An Analysis of the National Co morbidity Survey and the British Psychiatric Morbidity Survey,” Schizophrenia Bulletin 2008, 34 (1).

NAMI Commentary: Childhood adverse experiences have an important impact on the developing brain and body. Traumatic events raise the risk of many health concerns as has been well established in the ACE Study. The Shevlin study looks at large surveys of the population in the U.S. and England and looks more precisely at the relationship between psychosis and traumatic exposures. The study shed light on the increased risk of psychosis in a dose-dependent way for adverse experiences. This will help professionals and individuals alike better approach their interventions in individuals who are so impacted. Importantly, we do not know the mechanism of how multiple adverse events cause psychosis or what can be learned from people who are exposed to traumatic experiences and do not develop psychosis, or any other health concerns. Answers to these questions will help to develop better approaches and services.

Resilience and Illness Management Strategies

Two studies are noteworthy in this area.

Wellness Recovery Action Plan (WRAP)

WRAP, developed by Mary Ellen Copeland, was studied in six Ohio Counties in a randomized controlled study led by Cook. The 519 subjects were randomized to an eight-week, peer-led course or a wait list. The results showed improvements in symptoms, quality of life and hopefulness. This study was not done on a first episode population. Outcomes were measured at the end of the course and at six months. This is a strong design with a large number of subjects and builds scientific evidence to the first hand experience of people who have benefitted from WRAP.

Cook et al., “Results of a Randomized Controlled Trial of Mental Illness Self Management using Wellness Recovery Action Planning,” Schizophrenia Bulletin 10, March 2011.

NAMI Commentary: This is an important development in the field of peer-led resources to learn and practice self-management. Peers represent a powerful and unique perspective on self-management, and this study design lends scientific evidence to the experience of individual who have benefitted from the model. This study was not on people experiencing a first episode of psychosis, yet the learning and collaboration to foster self-management are likely quite applicable to this population as well.

Illness Management and Recovery

In a Swedish study, Fardig and his colleagues looked at an illness self-management tool for individuals with schizophrenia and compared it to treatment as usual. One of the approaches to promoting recovery and self-management in the field is called Illness Management and Recovery (IMR) and this has been the best-studied to-date. IMR in this study was done in a randomized, controlled trial of a small number (41) of individuals diagnosed with schizophrenia or schizoaffective disorder in community settings. Better results in coping and reduced suicidal ideation were key findings in the IMR group.

Fardig et al, "A Randomized Controlled Trial of Illness Management and Recovery in Person with Schizophrenia" Psychiatric Services 62, June 2011.

NAMI Commentary: Self-management is a central theme of recovery and this adds support to this model being one of the tools to get there in real world settings. The IMR model is largely staff led and has a strong research base overall but has not been studied in the first episode of psychosis. Finding the right self-management strategy is an important goal for any person experiencing psychiatric illness and WRAP and IMR each offer something validated by research in this area.

Note: Ask your clinic if they use IMR, peer directed WRAP or another model. If they don’t be sure to advocate that they do create access to these important self-management resources

Open Dialogues: A Comprehensive Approach in Finland

Western Lapland is a rural homogenous community in Finland of about 70,000 people. A group of community psychiatrists in this area have developed a comprehensive community-based approach called Open Dialogue for individuals, their families and communities and have followed the outcomes. The team is rapid-continuous (inpatient and outpatient), uses all natural supports and focuses on family understanding as well as individual understanding. They conclude that after two years “81 percent of patients did not have any residual psychotic symptoms. And 84 percent has returned to full time employment or studies. Only 33 percent had used neuroleptics medication.” They also report a decrease in the incidence of schizophrenia using these interventions.

Seikkula, Alakare and Asltonen, “The Comprehensive Open Dialogue Approach in Western Lapland: II Long-term Stability of Acute Psychosis Outcomes in Advanced Community Care,” Psychosis 2011, 1-13 First article.

NAMI Commentary: The model here is creative and compelling in a homogenous, Lutheran, rural area of Finland. Their comprehensive service model offers connection, rapid response, support and dialogue with individuals their families with validated understanding of their experience of psychosis, tolerance for uncertainty and individualized care. The research team shows that results in individuals with this model and cultural approach who are having first episode psychosis often improve with increased understanding and social support, with medicines being one tool among many. The design is naturalistic and not randomized controlled, which reduces but does not eliminate its potential impact. The model has not been applied to the diverse socioeconomic and racial composition of the U.S., and clinicians would be hard-pressed to find themselves in a coordinated and continuous service relationship with these supports unless it was specifically so designed. Yet the key principles of respect, fostering understanding, involving family and supports and dialoguing with the person with dedicated professionals has clear international applicability, even before this precise model is translated in the U.S. Reducing incidence of schizophrenia is a much more ambitious claim, and much more work would need to definitively demonstrate this impact.

Family Psychoeducation: NAMI Family-to-Family

Dixon and her colleagues studied NAMI’s signature Family-to-Family education program in the greater Baltimore and surrounding Maryland areas. The randomized design included 318 family members who either took the course when they called for it or were asked to wait three months or more. The difference in the two groups was studied and gains in coping and empowerment were found in the active group that got Family-to-Family over the wait-list group. This design helps to explain that time passing alone was not the key ingredient in the improvement.

Dixon et al., “Outcomes of a Randomized Study of a Peer Taught Family-to-Family Education Program for Mental Illness,” Psychiatric Services 62, June 2011.

NAMI Commentary: This is an affirming study for NAMI family members who teach Family-to-Family education programs who can now match their experience with scientific evidence. The study clearly demonstrates that Family-to-Family makes a difference in coping and empowerment of families. This is not a first episode of psychosis study, but coping and empowerment improvement is likely indicated for all families regardless of illness duration, as successful family functioning is a key ingredient in mental health and illness management.

Cognitive Enhancement Therapy and Early Schizophrenia

The researchers used Cognitive Enhancement Therapy (CET) in outpatients early in the course of schizophrenia. They randomized a small group of subjects (58) to receive CET or a similarly intensive nonspecific support. The results showed a clear advantage in employment, earnings and cognition for the CET group. They conclude, “CET can help facilitate employment in early schizophrenia by addressing the cognitive impairments that limit functioning in the disorder.” Eack, Hogarty, et al., “Effects on Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia Results from a Two-year, Randomized Trial,” Social Work Practice, 21 (1) 2011.

NAMI Commentary: CET is an exciting development in the field that endeavors to improve cognition through practice and social reinforcement. This is the first study to show its usefulness in the early years of schizophrenia. Though the sample size is limited, the results mirror impacts for more long-term schizophrenia and thereby have ample reason to be implemented in services that cater to this population.

Cognitive Behavior Therapy

The EPPIC Centre in Melbourne, Australia Psychosis Early Prevention and Intervention Centre Origen Youth Health

There are many resources to review from this leading center on Cognitive Behavior Therapy (CBT) and other psychosocial approaches. The best way to review this work is to go to the EPPIC Center website and to review what they have tried and learned in their system of care. This has led research in the use of CBT in the early episode of psychosis, but this summary alone does not do the center’s integrated and creative efforts justice.

NAMI Commentary: The comprehensive system of delivery in Melbourne has supported McGorry and his colleagues to develop psychosocial interventions for individuals with early onset psychosis that is creative and integrated.

Places to Watch for More Research

This important research work is happening in many countries each with its own delivery system, funding streams, culture and care models. For this reason, looking internationally to understand possible models and solutions is essential.

The International Society for Early Psychosis Association pulls together many of these international resources that are doing creative work in different cultural and system of delivery environments. Their eighth annual conference is in September 2012 in San Francisco.

Additional information on mental illness research can be found by visiting NIMH and NAMI’s Research section, which includes information on additional mental illness research opportunities, protection of research volunteers and more.