Hardly a family in America has been untouched by mental illness. As many as one third of American adults will suffer a diagnosable mental disorder sometime in their life, and 20 percent have a mental disorder at any given time. Although research on the causes and treatment of mental disorders remains vitally important—and indeed major advances are leading to better lives for increasing numbers of people—much greater effort than ever before needs to be directed to prevention. The Senate Appropriations Committee of the U.S. Congress believed that a strategic approach to the prevention of mental disorders was warranted. The Congress mandated the National Institute of Mental Health to enter into an agreement with the Institute of Medicine (IOM) to prepare an integrated report of current research with policy-oriented and detailed long-term recommendations for a prevention research agenda. The specific tasks of the IOM committee, as negotiated with NIMH and the co-funding agencies, were as follows: • Review the status of current research on the prevention of mental illness and problem behaviors and on the promotion of mental health throughout the life span. This should include an understanding of available research knowledge, research priorities, and research opportunities in the prevention research area. • Review the existing federal presence in the prevention of mental disorders and the promotion of mental health, spanning the continuum from research to policy and services. • Provide recommendations on federal policies and programs of ABSTRACT xi Ab ou t th is P D F fil e: T hi s ne w d ig ita l r ep re se nt at io n of t he o rig in al w or k ha s be en r ec om po se d fro m X M L fil es c re at ed f ro m t he o rig in al p ap er b oo k, n ot f ro m t he or ig in al ty pe se tti ng fi le s. P ag e br ea ks a re tr ue to th e or ig in al ; l in e le ng th s, w or d br ea ks , h ea di ng s ty le s, a nd o th er t y pe se tti ng -s pe ci fic fo rm at tin g, h ow ev er , c an no t b e re ta in ed , a nd s om e ty po gr ap hi c er ro rs m ay h av e be en a cc id en t a lly in se rte d. P le as e us e th e pr in t v er si on o f t hi s pu bl ic at io n as th e au th or ita tiv e ve rs io n fo r a ttr ib ut io n.

Reducing Risks for Mental Disorders: Frontiers for Preventive Intervention Research

Importance The ultra high-risk (UHR) criteria were introduced to prospectively identify patients at high risk of psychotic disorder. Although the short-term outcome of UHR patients has been well researched, the long-term outcome is not known. Objective To assess the rate and baseline predictors of transition to psychotic disorder in UHR patients up to 15 years after study entry. Design Follow-up study of a cohort of UHR patients recruited to participate in research studies between 1993 and 2006. Setting The Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service for UHR patients in Melbourne, Australia. Participants Four hundred sixteen UHR patients previously seen at the PACE clinic. Main Outcomes and Measures Transition to psychotic disorder, as measured using the Comprehensive Assessment of At-Risk Mental States, Brief Psychiatric Rating Scale/Comprehensive Assessment of Symptoms and History, or state public mental health records.  Results During the time to follow-up (2.4-14.9 years after presentation), 114 of the 416 participants were known to have developed a psychotic disorder. The highest risk for transition was within the first 2 years of entry into the service, but individuals continued to be at risk up to 10 years after initial referral. The overall rate of transition was estimated to be 34.9% over a 10-year period (95% CI, 28.7%-40.6%). Factors associated with transition included year of entry into the clinic, duration of symptoms before clinic entry, baseline functioning, negative symptoms, and disorders of thought content. Conclusions and Relevance The UHR patients are at long-term risk for psychotic disorder, with the highest risk in the first 2 years. Services should aim to follow up patients for at least this period, with the possibility to return for care after this time. Individuals with a long duration of symptoms and poor functioning at the time of referral may need closer monitoring. Interventions to improve functioning and detect help-seeking UHR patients earlier also may be indicated.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/1695587/yoi130064.pdf

Long-term follow-up of a group at ultra high risk ("prodromal") for psychosis: the PACE 400 study

OBJECTIVE: To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay transition to psychotic disorders for people at high risk. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status. REVIEW METHODS: Randomised trials comparing any psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising the results. RESULTS: 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range 51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference -0.07 (-0.14 to -0.01). Very low quality evidence for omega-3 fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions in transition to psychosis at 12 months. CONCLUSIONS: Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis.

https://www.bmj.com/content/bmj/346/bmj.f185.full.pdf

Early interventions to prevent psychosis: systematic review and meta-analysis.

OBJECTIVE: Over the last 15 years, a focus on early intervention in psychotic disorders has emerged. Initially, the early psychosis movement focused on timely recognition and phase-specific treatment of first-episode psychosis. However, early psychosis researchers suspected that pushing the point of intervention even further back to the prodromal phase of psychotic disorders may result in even better outcomes. This article reviews intervention research in the ultra-high-risk phase of psychotic disorders. DATA SOURCES: A literature search of intervention trials with ultra-high-risk cohorts published after 1980 was conducted on PubMed with the search terms prodrome and intervention. STUDY SELECTION: All published intervention trials with ultra-high-risk cohorts. DATA SYNTHESIS: The first generation of intervention trials indicated that both pharmacologic and psychological intervention strategies may be of value in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. CONCLUSIONS: Further controlled intervention trials with larger sample sizes are required in order to confirm and extend these findings. We argue that the clinical staging model provides a framework for the rationale and design of such studies, with simpler, safer, and more benign interventions being better candidates for first-line treatment, while more complex and potentially harmful treatments should be reserved for those cases in which response has failed to occur. Recent evidence indicates that neuroprotective agents, such as essential fatty acids, may be a suitable form of intervention for the ultra-high-risk phase of psychotic disorders, with a positive risk-benefit balance. Ethical aspects have become more salient given the recently observed declining transition rate in ultra-high-risk samples. We outline the key questions for the next generation of ultra-high-risk intervention trials.

Intervention in individuals at ultra-high risk for psychosis: a review and future directions.

PAUL CHADWICK, MAX BIRCHWOOD, AND PETER TROWER: Cognitive Therapy for Delusions, Voices and Paranoia. John Wiley & Sons, Chichester, England, 1996, 210 pp., $55.00, ISBN 0-471-93888-2. It may seem anachronistic now, but there was a time when clinicians took seriously the psychotherapeutic treatment of schizophrenics and other psychotic patients. There used to be genuine optimism, at influential institutions such as Austin Riggs, that intensive psychoanalytic psychotherapy would be successful in alleviating psychotic symptomatology. With the remarkable efficacy of pharmacological treatments, clinicians currently pay little attention to the patient's internal psychological make-up, other than to use rehabilitation or psychoeducational approaches that represent efforts to help the patient accommodate to disturbing residual symptoms and functional deficits. In their new volume, Chadwick, Birchwood, and Trower challenge this pervasive skepticism, and take the psychotherapy of psychosis quite seriously. They claim that delusions, auditory hallucinations, and paranoia are amenable to relatively brief (20-30 sessions) psychotherapeutic interventions. Psychotherapy works, as they see it, because psychotic symptoms are merely exaggerations of normal psychological phenomena. Symptoms are not discontinuous with normal experience; rather, they are manifestations of basic cognitive mechanisms, regarding how people interpret and make inferences and attributions about events. As such, psychotic experiences will respond to cognitive therapy interventions. Although cognitive therapists have traditionally found psychotic patients to be untreatable, the authors label their approach "cognitive therapy," and scrupulously examine the beliefs and evaluations underlying psychotic experiences, engaging floridly paranoid individuals in ongoing psychotherapy. Using an ABC framework, they conceptualize all experiences and interactions in terms of Activating events, Beliefs, and emotional (or behavioral) Consequences. Delusions and paranoid thinking reflect beliefs about certain events and experiences, once those events are placed within an appropriate context. Even perceptual distortions, such as voices, are considered activating events, with associated beliefs and evaluations. As Chadwick et al. view it, these beliefs are the source of problems, not the psychotic experiences per se, and these beliefs may be changed. They will not directly confront a delusions, but they will subtly call it a belief (as opposed to a fact), challenge inconsistencies within the delusional logic, and ask about reactions to hypothetical contradictions. All these strategies are attempts to access the patient's self-evaluations. These three British psychologists ground their therapy in general social psychological theory, which may not be familiar to nonpsychologists. For example, they discuss self-other attributions, but make no mention of the concept of "projection." They speak of other-self or self-self evaluations in ways that are quite similar to object relations theorists, and yet there is no reference to this way of thinking. Considering the long tradition of conceptualizing psychosis in terms of lack of ego boundaries, it would have been useful to discuss the notion of paranoid delusions as a defense against fear of merger. …

Cognitive Therapy for Delusions, Voices and Paranoia

Objective: Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder, or at least of reducing the impact of such a disorder if it does develop. The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk (UHR) of psychosis. Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder.Method: The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were randomized to one of three treatment groups: cognitive therapy plus risperidone (CogTher + Risp: n = 43); cognitive therapy plus placebo (CogTher + Placebo: n = 44); and supportive counselling + placebo (Supp + Placebo; n = 28). A fourth group of young people wh...

Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: Study design and baseline characteristics

OBJECTIVE Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

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Papers

Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: Study design and baseline characteristics

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients.