Editor-in-Chief: John A. Talbott, MD
ISSN: 0022-3018
Online ISSN: 1539-736X
Frequency: 12 issues / year
Ranking: Psychiatry 51/120
Impact Factor: 1.812
Article Summaries
   

May 2015 Article Summaries

Special issue on “Early Detection and Intervention for People with Psychosis” 

 

1. EARLY DETECTION AND INTERVENTION FOR PEOPLE WITH PSYCHOSIS. GETTING TO THE BOTTOM LINE

Faith Dickerson, PhD, MPH

The articles in this special issue bring together some recent developments in the field of early detection and intervention for people with psychosis. The issue includes 13 articles by some of the preeminent researchers in this rapidly evolving field. In the US, research on the topic has taken its cue from investigators in Australia, Canada, England, Denmark, and other countries, some of whose work is represented here. The issue includes 5 articles focused primarily on the prodrome or the prediction of psychosis, 7 that are focused on the treatment or outcome of first episode psychosis, and one on immunologic-based medication treatments. Among the contributions are original research reports, review articles, and personal commentaries. What is the reader to conclude from this collection of articles that represent a detailed presentation of early intervention studies? Clearly there is now urgency to improve outcomes for patients with schizophrenia starting early in the illness or even before the illness begins, to cast a wider net in identifying vulnerable individuals, and to provide specialized services for high risk and for early onset patients. In addition, and as demonstrated by several articles here, unraveling the etiological factors of schizophrenia and determining the full scope of patient outcomes is no easy task. It requires large collaborative efforts such as NAPLS and the use of population-based data such as those from the US military or from cohorts based on national health systems. There is a need for approaches that integrate biological and clinical markers and for long-term observational studies as well as clinical trials. The goal is the development of practical and effective methods for early detection and intervention. Such methods would have a profound effect on the health and well-being of all individuals affected by these devastating disorders.

 

2. EARLY INTERVENTION IN PSYCHOSIS: OBVIOUS, EFFECTIVE

Patrick D. McGorry, MD, PhD, FRCP, FRANZCP.

Although the efficacy of modern treatments in psychiatry is comparable with those in general medicine (Leucht et al, 2012), the reductions in mortality and morbidity seen in cancer and cardiovascular disease over recent decades have proven more elusive in serious mental disorders, such as schizophrenia and other psychoses (Insel, 2010). The conventional wisdom is that such progress must await the discovery of new dramatically more effective treatments based on target mechanisms; however, this has not been the main reason for the improved outcome in the main medical disease categories. Prevention has played a role in reducing the incidence of cardiovascular disease and some cancers, and some new therapeutic strategies have emerged recently; however, early diagnosis and the sustained and sophisticated delivery of existing therapies have been the decisive factors in improving outcomes.

 

3. PREDICTORS OF THE ONSET OF SCHIZOPHRENIA IN US MILITARY PERSONNEL

Natalya S. Weber, MD, MPH, Rakel A. Larsen, MS, Robert H. Yolken, MD, David N. Cowan, PhD, MPH, Michael R. Boivin, MD, MPH, David W. Niebuhr, MD, MPH, MS.    

Alterations in immune response may be an important component in the etiopathogenesis of schizophrenia and bipolar disorder. We examined associations of pentraxin-3 (PTX3) with the onset of schizophrenia or bipolar disorder. We tested pre-onset serum specimens from 160 US military service members who were later diagnosed with schizophrenia or bipolar disorder and 160 matched controls without psychiatric disorders. Lower serum levels of PTX3 were predictive of schizophrenia but not of bipolar disorder. Subjects with below median PTX3 levels had a 3.0 (CI: 1.6, 5.7) odds ratio for schizophrenia onset in the multivariable logistic regression model controlling for demographic and military variables. The test for trends was significant (p = 0.002) with the likelihood increasing as the levels of PTX3 decreased. Crude and adjusted categorized levels were not predictive of bipolar disorder. A lower level of inflammatory response indicated by PTX3 might be implicated in developing schizophrenia.

 

4. ATTENUATED PSYCHOSIS SYNDROME: A NEW DIAGNOSTIC CLASS?

William T. Carpenter, MD.

Early detection and treatment of illness is fundamental in providing optimal health care. However, this is a major challenge in mental illness where diagnoses depend on symptom manifestation and the symptoms are often on a continuum with behaviors observed in the non-ill population. During the past 25 years, substantial progress has been made in identifying clinical high risk for psychoses with extensive validation and the beginning of treatment trials for symptom reduction and secondary prevention of psychoses. Attenuated Psychosis Syndrome is placed in Section 3 of DSM-5 as a new disorder for further study. 

 

5. NORTH AMERICAN PRODROME LONGITUDINAL STUDY (NAPLS 2): THE PRODROMAL SYMPTOMS

Jean Addington, PhD, Lu Liu, MSc, Lisa Buchy, PhD, Kristin S. Cadenhead, MD, Tyrone D. Cannon, PhD, Barbara A. Cornblatt, PhD, Diana O. Perkins, MD, Larry J. Seidman, PhD, Ming T. Tsuang, MD, Elaine F. Walker, PhD, Scott W. Woods, MD, Carrie E. Bearden, PhD, Daniel H. Mathalon, MD, and Thomas H. McGlashan, PhD.

We describe the prodromal symptoms of 764 clinical high risk (CHR) participants recruited in the multi-site North American Prodrome Longitudinal Study (NAPLS). Symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline and 6, 12, 18 and 24 month follow-ups. Clinical outcome at the 2-year assessment was categorized as psychotic, prodromal progression, symptomatic or in remission. The majority of the CHR sample (93%) met criteria for the attenuated positive symptoms syndrome (APSS). Unusual thought content, disorganized communication and overall ratings on disorganized symptoms differentiated those who transitioned to psychosis from the other clinical outcome groups. Suspiciousness and total positive symptoms differentiated those in remission from the other clinical outcome groups.

 

6. BRAIN IMAGING DURING THE TRANSITION FROM PSYCHOSIS PRODROME TO SCHIZOPHRENIA

Yoonho Chung, BS, Tyrone D. Cannon, PhD.

Recent work conducted within the prodromal risk paradigm suggests that progressive change in brain structure and function occurs around the time when clinically high-risk individuals transition into full-blown psychosis, effects that cannot be explained by exposure to medications or illness chronicity. This article reviews recent work bearing on the question of the timing of onset and course of brain changes, focusing on structural MRI, diffusion tensor imaging, and resting state connectivity MRI, in association with the onset and course of psychosis. We conclude with a consideration of potential mechanisms underlying progressive tissue changes during the prodromal phase of schizophrenia and implications for prevention.

 

7. EVIDENCE-BASED EARLY INTERVENTIONS FOR INDIVIDUALS AT CLINICAL HIGH RISK FOR PSYCHOSIS:  A REVIEW OF TREATMENT COMPONENTS

Elizabeth Thompson, MA, Zachary B. Millman, BA, Nana Okuzawa, MD, Vijay Mittal, PhD, Jordan DeVylder, PhD, Travis Skadberg, AA, Robert W. Buchanan, MD, Gloria M. Reeves, MD, Jason Schiffman, PhD.

Youth and young adults at clinical high risk (CHR) for psychosis experience a broad range of difficulties including attenuated psychotic symptoms, comorbid concerns, functional impairments, and family and interpersonal stress. Given emerging evidence that early interventions may improve functioning and reduce symptomatology while also lowering risk of transition to full-threshold psychosis, several randomized control trials (RCTs) have systematically evaluated the efficacy of CHR treatment approaches. This paper summarizes psychosocial intervention approaches that have demonstrated efficacy in treating people at CHR. We propose an empirically-based, flexible, and comprehensive modularized approach to early intervention that meets the varying needs of individuals experiencing CHR-related distress and dysfunction.

 

8. FROM TREATING TO PREVENTING PSYCHOSIS: PERSONAL PERSPECTIVES

Thomas H. McGlashan, MD.

The psychoanalytic treatment model of neurotic disorders was applied “experimentally”, usually without concomitant pharmacotherapy, to psychotic disorders in the mid to late 20th century at a private institution (Chestnut Lodge) in Maryland. A long term follow up (by this author) documented such an approach to be ineffective but suggested that initial treatment earlier in the development of disorder might prevent or ameliorate the “dementia” of dementia praecox. The sectorized Norwegian health care system made it possible to engineer early detection of first psychosis in an “experimental” health care sector and compare their outcome to that of first onset patients from two control “usual detection” health care sectors. Early detection was engineered in the experimental sector with educational campaigns about the signs and symptoms of first psychosis. Early detection and treatment resulted in a significantly better symptomatic, social and instrumental outcome in the experimental sectors compared to “usual detection” sectors, a difference that lasted up to a ten year follow up. Intervention timing may be far more important than intervention type in the overall strategy of antipsychotic interventions.

 

9. EARLY INTERVENTION FOR PSYCHOSIS: A CANADIAN PERSPECTIVE

Srividya Iyer, PhD , Gerald Jordan, MA, Kathleen MacDonald, MSc,  Ridha Joober, MD, PhD, Ashok Malla, MB, FRCPC.  

We describe a leading Canadian early intervention EI program’s approach to enhancing access and providing specialized phase-specific treatment. Learnings from this program’s research/evaluation indicate that EI can significantly improve service user and family engagement. Achieving and maintaining symptom remission may be important for better social and occupational functioning in first-episode psychosis (FEP). Our program demonstrates the feasibility of establishing and sustaining an open referral, rapid-response system to address the chronic systemic problems of long waiting lists and barriers to access. We argue that an integrated clinical-research program based on specialized EI guidelines can significantly improve outcomes and advance FEP research.

 

10. THE RAISE CONNECTION PROGRAM FOR EARLY PSYCHOSIS: SECONDARY OUTCOMES AND MEDIATORS AND MODERATORS OF IMPROVEMENT

Leslie Marino, MD, MPH, Ilana Nossel, MD, Jean C. Choi, MS, Keith Neuchterlein, PhD, Yuanjia Wang, PhD, Susan Essock, PhD, Melanie Bennett, PhD, Karen McNamara PhD, MSW, Sapna Mendon, MSW, Lisa Dixon, MD, MPH.

We explored secondary outcomes of a coordinated specialty care program for persons with early psychosis, including quality of life and recovery, as well as to explore mediators and moderators of improvement in occupational and social functioning and symptoms. Sixty-five individuals across two sites were enrolled and received services for up to two years. Trajectories for individuals’ outcomes over time were examined using linear and quadratic mixed-effects models. Baseline prognostic factors of participant improvement in social and occupational functioning were explored. Results demonstrate that the program was effective in improving quality of life and recovery over time. Furthermore, processing speed was identified as a significant moderator of improvement in occupational GAF, and treatment fidelity, engagement, and family involvement were identified as mediators of improvement in social and occupational functioning.

 

11. METACOGNITIVE CAPACITY AS A PREDICTOR OF INSIGHT IN FIRST EPISODE PSYCHOSIS

Jenifer L. Vohs, PhD, Paul H. Lysaker, PhD, Emily Liffick, MD,  Michael M. Francis, MD, Bethany L. Leonhardt, PsyD, Alison James, MS, Kelly D. Buck, RN, Jay A. Hamm, PsyD, Kyle S. Minor, PhD, Nikki Mehdiyoun, MA,  Alan Breier, MD.

Impaired insight is common in first episode of psychosis (FEP). Impaired metacognition, or the ability to form integrated representations of self and others, is a promising potential contributor to poor insight in FEP. To explore this possibility, we assessed insight and metacognition in 40 individuals with FEP and then examined the relationship between these areas and social cognition domains, neurocognitive domains, and psychotic symptoms. Correlation analyses revealed that improved insight was associated with higher metacognition, better vocabulary and Theory of Mind scores, and fewer symptoms. Results support the need to develop an integrative therapeutic approach focused on improving metacognition, hence addressing poor insight in FEP.

 

12. AN OVERVIEW OF OUTCOMES IN FIRST EPISODE PSYCHOSES IN THE MRC ÆSOP-10 STUDY

Camice J. Revier, BS , Ulrich Reininghaus, PhD, Paul Fearon, MD, Robin M. Murray, DSc, Gillian Doody, PhD, Tim Croudace, PhD, Paola Dazzan, PhD, Margaret Heslin, PhD, Julia Lappin, PhD5, Ben Lomas, MD, Kim Donoghue, PhD, Craig Morgan, PhD, Peter B. Jones, MD.

We have synthesised information on mortality, clinical and social outcomes from the ÆSOP-10 multicenter study, a 10-year follow up of a large epidemiologically characterised cohort of 557 people with first-episode psychosis. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs, social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact as compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these conditions were first described.

 

13. SUICIDAL BEHAVIOR AND MORTALITY IN FIRST-EPISODE PSYCHOSIS

Merete Nordentoft, DrMSc, Trine Madsen, PhD and Izabela Fedyszyn, PhD.

In schizophrenia and other psychotic disorders, the lifetime risk of suicide death is estimated to be 5.6%. The risk is particularly high during the first year of the initial contact with mental health services, being almost twice as high as in the later course of the illness. The most consistently reported risk factor for suicide among people with psychotic disorders is a history of attempted suicide and depression. Suicide risk in psychosis in Denmark decreased over time, most likely due to improved quality of inpatient and outpatient services. There is a high proportion of young people with first-episode psychosis who attempted suicide before their first contact with mental health services. This finding suggests that the mortality rates associated with psychotic disorders may be underreported due to suicide deaths taking place prior to first treatment contact. Data from different studies indicate that the risk of suicide attempt during first year of treatment is as high as 10 percent. The most important risk factors for attempted suicide after first contact are young age, female gender, suicidal plans and a history of suicide attempt. Early intervention services are helpful in first-episode psychosis, and staff members should monitor the risk of suicide and develop and revise crisis plans.

 

14. THE POTENTIAL OF PERIPHERAL BIOMARKERS TO ADVANCE PERSONALIZED MEDICINE APPROACHES FOR SCHIZOPHRENIA

David Cox, MSc, Man Chan, PhD, Sabine Bahn, Prof.

In this review, we discuss studies relating to dysfunctions of the immune system in schizophrenia patients and the effects of antipsychotic medication on the molecular components of these systems. Immune system dysfunction may in part be related to genetic risk factors for schizophrenia, but there is substantial evidence that a wide range of environmental factors, ranging from exposure to infectious agents such as influenza and Toxoplasma gondii to HPA axis dysfunction, play an important role in the etiopathogenesis of schizophrenia. Ongoing research efforts, testing therapeutic efficacy of anti-inflammatory agents used as add-on medications are also discussed. From a therapeutic perspective, these represent the initial steps towards novel treatment approaches and more effective patient care.

 

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Dr. Talbott and Lippincott Williams & Wilkins
wish to thank the
University of Maryland School of Medicine
Department of Psychiatry
for their support of
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