Characterization and prediction of individual functional outcome trajectories in schizophrenia spectrum disorders (PREDICTS study): Study protocol.

Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.

Do anxiety and depression symptoms moderate the effect of motivational enhancement therapy as a pretreatment to dialectical behaviour therapy skills training? A follow-up analysis of a pilot randomised controlled trial for youth.

AIM: We conducted a follow-up analysis of a pilot randomised controlled trial to examine whether baseline depression and anxiety symptoms moderated the impact of a motivational enhancement therapy (MET) pretreatment to dialectical behaviour therapy skill training (DBT-ST) for EA experiencing emotion dysregulation. METHODS: All participants completed a 12-week DBT-ST group intervention and participants in the MET/DBT-ST condition also completed a 4-week group MET pretreatment. Nineteen MET/DBT-ST participants and 26 DBT-ST only participants completed the treatment as per protocol. RESULTS: Baseline anxiety and depression symptoms moderated the impact of the MET pretreatment for participants' reductions in emotion dysregulation and psychological distress, respectively, at a 3-month follow-up: participants with more severe baseline symptoms benefited more from the pretreatment. However, baseline symptoms did not moderate the effect of MET immediately after treatment. CONCLUSIONS: These results identified for whom MET is most effective as a pretreatment for DBT-ST amongst a heterogenous sample of EA in a real-world setting.

Motivational Enhancement as a Pretreatment to a Transdiagnostic Intervention for Emerging Adults with Emotion Dysregulation: A Pilot Randomized Controlled Trial.

OBJECTIVE: New approaches are needed to help the large number of emerging adults (EA) presenting with early-stage mental health problems. The goal of this pilot study was to carry out a randomized controlled trial to investigate whether motivational enhancement therapy (MET) improved the treatment effects of a 12-week psychological intervention, Dialectical Behaviour Therapy Skills Training (DBT-ST), for EA presenting in the early stages of mental health difficulties. Participants were recruited from the Youth Wellness Centre at St. Joseph's Healthcare Hamilton and McMaster University's Student Wellness Centre in Hamilton, Canada. METHODS: Seventy-five participants were randomized to receive MET followed by DBT-ST or to DBT-ST alone. We assessed psychological distress, emotion dysregulation, and depression and anxiety symptoms as outcomes. RESULTS: We found that both treatment groups had significant reductions in emotional dysregulation, psychological distress, depression, and anxiety at post-treatment and at the three-month follow-up. Participants assigned to MET pre-treatment experienced greater improvement in psychological distress at the end of treatment. CONCLUSION: This pilot study provides preliminary evidence of the potential augmentation of DBT-ST using MET in a real-world setting. Future studies should examine whether MET uniquely augments DBT-ST through the use of a comparable pre-treatment control group.

OBJECTIF: De nouvelles approches sont nécessaires pour aider le grand nombre d'adultes émergeants (AE) qui présentent des problèmes de santé mentale au stade précoce. La présente étude pilote avait pour but d'exécuter un essai randomisé contrôlé afin de rechercher si la thérapie d'amélioration motivationnelle (TAM) améliorait les effets du traitement d'une intervention psychologique de 12 semaines, soit la formation technique à la thérapie comportementale dialectique (FT-TCD), pour les AE qui présentent les premiers stades de difficultés de santé mentale. Les participants ont été recrutés au centre Youth Wellness de St. Joseph's Healthcare Hamilton et au centre Student Wellness de l'Université McMaster, à Hamilton, Canada. MÉTHODES: Soixante-quinze participants ont reçu au hasard la TAM suivie de la FT-TCD ou uniquement la FT-TCD. Nous avons évalué la détresse psychologique, la dérégulation émotionnelle, et les symptômes dépressifs et anxieux comme résultats. RÉSULTATS: Nous avons constaté que les deux groupes du traitement avaient des réductions significatives de la dérégulation émotionnelle, de la détresse psychologique, de la dépression et de l'anxiété au post-traitement et au suivi de 3 mois. Les participants affectés à la TAM de prétraitement ont eu une plus grande amélioration de la détresse psychologique en fin de traitement. CONCLUSION: Cette étude pilote offre des données probantes préliminaires de l'augmentation potentielle de la FT-TCD utilisant la TAM dans une situation réelle. Les futures études devraient examiner si la TAM n'augmente seulement la FT-TCD que par le recours à un groupe témoin prétraitement comparable.

You say "schizophrenia" and I say "psychosis": Just tell me when I can come off this medication.

Individuals experiencing a first episode of psychosis are likely to respond well to treatment with antipsychotic medications. Of those treated for a first episode of schizophrenia, three out of four can expect to achieve remission. The question of how long antipsychotic medication should be continued has been a topic of heated debate in the field. Longitudinal studies of individuals diagnosed with a first episode of psychosis have reported that as many as 30% may be able to come off of medications without relapsing while treatment discontinuation studies have found that very few patients remain in remission off of medication. This paper reviews the literature on relapse rates following a first episode of schizophrenia and identifies factors that contribute to the discrepancies in the rates reported. These factors include sampling considerations, the distribution of psychiatric diagnoses, the duration of follow-up, the rate of medication discontinuation and the criteria used to define illness recurrence. We propose that individuals for whom the diagnosis of their first psychotic episode is determined with ongoing follow-up to be due to schizophrenia are at extremely high risk of relapse and should be advised to continue antipsychotic medication for the long-term. Those whose first episode of psychosis is determined to be due to other causes are also at high risk of illness recurrence off medications. Recommendations for maintenance treatment should be tailored to reflect the risk of relapse and sequelae of relapse associated with specific causes of first episode psychosis.

Rethinking service design for youth with mental health needs: The development of the Youth Wellness Centre, St. Joseph's Healthcare Hamilton.

AIM: This article describes the development and design of the Youth Wellness Centre (YWC), an innovative, youth-friendly centre providing mental health and addiction services for emerging adults aged 17 to 25 in Hamilton, Canada. We also report on demographic and clinical characteristics of clients to evaluate how the YWC is serving populations at increased risk of developing mental disorders. METHODS: Data were extracted from clinic databases for 1520 youth at the YWC between March 2015 and 2018 to report on demographic characteristics, clinical profiles, primary presenting problems, service use and overall satisfaction with services. RESULTS: Marginalized groups, particularly street-involved individuals and LGBTQ+ youth, are highly represented at the YWC, keeping with the centre's mandate of reaching at-risk populations. Youth at the YWC carry significant mental health burdens, with 80.8% having a history of suicidal ideation and 32.8% having a history of a substance use disorder. The primary route of referral is self-referral and the number of new clients has increased by nearly 20% in the first 3 years of operations. Overall satisfaction with the centre is on par with or slightly above provincial averages. CONCLUSIONS: The YWC was developed to meet the mental health needs of transition-aged youth in Hamilton by providing early intervention, system navigation and transition services. The success of the YWC in reaching high-risk youth is demonstrated by the significant proportion of clients reporting demographic and clinical risk factors associated with increased risk for development of mental disorders. The increasing referrals to the YWC highlight the ongoing need for similar services.

Understanding and Managing Treatment Adherence in Schizophrenia.

Schizophrenia is a chronic, debilitating and costly illness. The course of illness is often exacerbated by relapses which are associated with negative outcomes including rehospitalisation. The most important risk factor associated with relapse is medication nonadherence. Medication nonadherence is not specific to schizophrenia and is an issue across all of medicine. The objective of this paper is to present a narrative review which synthesizes the rates and predictors of medication nonadherence, as well as associated interventions, across schizophrenia, first episode psychosis and general medicine. Given the breadth of these topics, this paper does not aim to present a complete review of the data but rather a concise synthesis of several lines of research in order to provide a general framework for approaching this important topic. Overall, this paper identifies that rates and risk factors of nonadherence in schizophrenia are similar to those reported in general medicine. Rates of adherence are estimated at 50% for both. Predictors of nonadherence were also quite similar between various illnesses, with lack of insight, poor family support and substance abuse often being highlighted. Well studied approaches of improving adherence include simplifying medication regimens, psychoeducation, engaging family support and use of long-acting injectable antipsychotics. Emerging interventions included text-message reminders, financial incentives and MyCite technology. Additionally, several evidence based interventions were identified in general medicine that may have applicability in schizophrenia and first episode psychosis. Lastly, avenues of future research were identified including the need to further characterize the dichotomy between adherence, partial adherence and nonadherence.

Investigating service features to sustain engagement in early intervention mental health services.

AIM: To understand what service features would sustain patient engagement in early intervention mental health treatment. METHODS: Mental health patients, family members of individuals with mental illness and mental health professionals completed a survey consisting of 18 choice tasks that involved 14 different service attributes. Preferences were ascertained using importance and utility scores. Latent class analysis revealed segments characterized by distinct preferences. Simulations were carried out to estimate utilization of hypothetical clinical services. RESULTS: Overall, 333 patients and family members and 183 professionals (N = 516) participated. Respondents were distributed between a Professional segment (53%) and a Patient segment (47%) that differed in a number of their preferences including for appointment times, individual vs group sessions and mode of after-hours support. Members of both segments shared preferences for many of the service attributes including having crisis support available 24 h per day, having a choice of different treatment modalities, being offered help for substance use problems and having a focus on improving symptoms rather than functioning. Simulations predicted that 60% of the Patient segment thought patients would remain engaged with a Hospital service, while 69% of the Professional segment thought patients would be most likely to remain engaged with an E-Health service. CONCLUSIONS: Patients, family members and professionals shared a number of preferences about what service characteristics will optimize patient engagement in early intervention services but diverged on others. Providing effective crisis support as well as a range of treatment options should be prioritized in the future design of early intervention services.

Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia.

Although some studies have suggested that relapse may be associated with antipsychotic treatment resistance in schizophrenia, the number and quality of studies is limited. The current analysis included patients with a diagnosis of first-episode schizophrenia or schizoaffective disorder who met the following criteria: (1) referral to the First-Episode Psychosis Program between 2003 and 2013; (2) treatment with an oral second-generation antipsychotic according to a standardized treatment algorithm; (3) positive symptom remission; (4) subsequent relapse (i.e., second episode) in association with non-adherence; and (5) reintroduction of antipsychotic treatment with the same agent used to achieve response in the first episode. The following outcomes were used as an index of antipsychotic treatment response: changes in the brief psychiatric rating scale (BPRS) total and positive symptom scores and number of patients who achieved positive symptom remission and 20 and 50% response. A total of 130 patients were included in the analyses. Although all patients took the same antipsychotic in both episodes, there were significant episode-by-time interactions for all outcomes of antipsychotic treatment response over 1 year in favor of the first episode compared to the second episode (50% response rate: 48.7 vs. 10.4% at week 7; 88.2 vs. 27.8% at week 27, respectively). Although antipsychotic doses in the second episode were significantly higher than those in the first episode, results remained unchanged after adjusting for antipsychotic dose. The present findings suggest that antipsychotic treatment response is reduced or delayed in the face of relapse following effective treatment of the first episode of schizophrenia.

Modeling the mental health service utilization decisions of university undergraduates: A discrete choice conjoint experiment.

OBJECTIVE: We modeled design factors influencing the intent to use a university mental health service. PARTICIPANTS: Between November 2012 and October 2014, 909 undergraduates participated. METHOD: Using a discrete choice experiment, participants chose between hypothetical campus mental health services. RESULTS: Latent class analysis identified three segments. A Psychological/Psychiatric Service segment (45.5%) was most likely to contact campus health services delivered by psychologists or psychiatrists. An Alternative Service segment (39.3%) preferred to talk to peer-counselors who had experienced mental health problems. A Hesitant segment (15.2%) reported greater distress but seemed less intent on seeking help. They preferred services delivered by psychologists or psychiatrists. Simulations predicted that, rather than waiting for standard counseling, the Alternative Service segment would prefer immediate access to E-Mental health. The Usual Care and Hesitant segments would wait 6 months for standard counseling. CONCLUSIONS: E-Mental Health options could engage students who may not wait for standard services.

Characterizing outcome preferences in patients with psychotic disorders: a discrete choice conjoint experiment.

The majority of individuals with schizophrenia will achieve a remission of psychotic symptoms, but few will meet criteria for recovery. Little is known about what outcomes are important to patients. We carried out a discrete choice experiment to characterize the outcome preferences of patients with psychotic disorders. Participants (N=300) were recruited from two clinics specializing in psychotic disorders. Twelve outcomes were each defined at three levels and incorporated into a computerized survey with 15 choice tasks. Utility values and importance scores were calculated for each outcome level. Latent class analysis was carried out to determine whether participants were distributed into segments with different preferences. Multinomial logistic regression was used to identify predictors of segment membership. Latent class analysis revealed three segments of respondents. The first segment (48%), which we labeled "Achievement-focused," preferred to have a full-time job, to live independently, to be in a long-term relationship, and to have no psychotic symptoms. The second segment (29%), labeled "Stability-focused," preferred to not have a job, to live independently, and to have some ongoing psychotic symptoms. The third segment (23%), labeled "Health-focused," preferred to not have a job, to live in supervised housing, and to have no psychotic symptoms. Segment membership was predicted by education, socioeconomic status, psychotic symptom severity, and work status. This study has revealed that patients with psychotic disorders are distributed between segments with different outcome preferences. New approaches to improve outcomes for patients with psychotic disorders should be informed by a greater understanding of patient preferences and priorities.

Preferences for Early Intervention Mental Health Services: A Discrete-Choice Conjoint Experiment.

OBJECTIVE: Early intervention services (EISs) for mental illness may improve outcomes, although treatment engagement is often a problem. Incorporating patients' preferences in the design of interventions improves engagement. A discrete-choice conjoint experiment was conducted in Canada to identify EIS attributes that encourage treatment initiation. METHODS: Sixteen four-level attributes were formalized into a conjoint survey, completed by patients, family members, and mental health professionals (N=562). Participants were asked which EIS option people with mental illness would contact. Latent-class analysis identified respondent classes characterized by shared preferences. Randomized first-choice simulations predicted which hypothetical options, based on attributes, would result in maximum utilization. RESULTS: Participants in the conventional-service class (N=241, 43%) predicted that individuals would contact traditional services (for example, hospital location and staffed by psychologists or psychiatrists). Membership was associated with being a patient or family member and being male. Participants in the convenient-service class (N=321, 57%) predicted that people would contact services promoting easy access (for example, self-referral and access from home). Membership was associated with being a professional. Both classes predicted that people would contact services that included short wait times, direct contact with professionals, patient autonomy, and psychological treatment information. The convenient-service class predicted that people would use an e-health model, whereas the conventional-service class predicted that people would use a primary care or clinic-hospital model. CONCLUSIONS: Provision of a range of services may maximize EIS use. Professionals may be more apt to adopt EISs in line with their beliefs regarding patient preferences. Considering several perspectives is important for service design.

Values in First-Episode Schizophrenia.

OBJECTIVE: Functional impairment continues to represent a major challenge in schizophrenia. Surprisingly, patients with schizophrenia report a level of happiness comparable with control subjects, even in the face of the prominent functional deficits, a finding at odds with evidence indicating a positive relation between happiness and level of functioning. In attempting to reconcile these findings, we chose to examine the issue of values, defined as affectively infused criteria or motivational goals used to select and justify actions, people, and the self, as values are related to both happiness and functioning. METHODS: Fifty-six first-episode patients in remission and 56 healthy control subjects completed happiness and values measures. Statistical analyses included correlations, analysis of variance, structural equation modelling, and smallest space analysis. RESULTS: Results indicated that patients with schizophrenia placed significantly greater priority on the value dimensions of Tradition (P = 0.02) and Power (P = 0.03), and significantly less priority on Self-direction (P = 0.007) and Stimulation, (P = 0.008). CONCLUSIONS: Essentially, people with schizophrenia place more emphasis on the customs and ideas that traditional culture or religion provide in conjunction with a decreased interest in change, which is at odds with the expectations of early adulthood. This value difference could be related to functional deficits. To this point, we have assumed that people hold to the same values that guided them before the illness' onset, but this may not be the case. Our study indicates that values differ in people with schizophrenia, compared with control subjects, even early in the illness and in the face of symptomatic remission.

Why are the outcomes in patients with schizophrenia so poor?

Despite many advances in the treatment of schizophrenia over the past 50 years, the outcomes for many patients with schizophrenia remain poor. While the majority of patients with a first episode of schizophrenia may be able to achieve and maintain a remission of symptoms, only 1 in 7 patients are likely to meet criteria for recovery. These findings could be easily reconciled if schizophrenia could be established to be a progressive brain disease. Results from longitudinal studies of brain structure, cognitive functioning, and clinical outcomes, however, do not support this view. The poor outcomes so commonly observed are likely best explained by poor access to treatment, poor engagement in ongoing care, poor treatment response, and poor adherence together with the cumulative negative impact of substance abuse, comorbid psychiatric disorders, cognitive deficits, and multiple social determinants of health.

Event-related brain potential study of semantic priming in unaffected first-degree relatives of schizophrenia patients.

Schizophrenia is associated with abnormalities in using meaningful stimuli to activate or prime related concepts in semantic long-term memory. A neurophysiological index of this activation is the N400, an event-related brain potential (ERP) waveform elicited by meaningful stimuli, which is normally reduced (made less negative) by relatedness between the eliciting stimulus and preceding ones (N400 semantic priming). Schizophrenia patients exhibit N400 semantic priming deficits, suggesting impairment in using meaningful context to activate related concepts. To address whether this abnormality is a trait-like marker of liability to schizophrenia or, alternatively, a biomarker of the illness itself, we tested for its presence in schizophrenia patients' unaffected biological relatives. We recorded ERPs from 12 unaffected first-degree relatives of schizophrenia patients, 12 schizophrenia patients, and 12 normal control participants (NCPs) who viewed prime words each followed at 300- or 750-ms stimulus-onset asynchrony (SOA) by an unrelated or related target word, or a nonword, in a lexical-decision task. As expected, across SOAs, NCPs exhibited smaller (less negative) N400 amplitudes for related versus unrelated targets. The same pattern held in relatives, whose N400 amplitudes for related and unrelated targets did not differ from NCPs'. In contrast, consistent with previous results, schizophrenia patients exhibited larger N400 amplitudes than NCPs (and relatives) for related targets, such that patients' N400 amplitudes for related and unrelated targets did not differ. N400 amplitudes for unrelated targets did not differ between the three groups. Thus, N400 semantic priming deficits in a visual word-pair paradigm may be an illness biomarker for schizophrenia.

Risk of symptom recurrence with medication discontinuation in first-episode psychosis: a systematic review.

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

Meta-regression analysis of placebo response in antipsychotic trials, 1970-2010.

OBJECTIVE: Large placebo response presents a major challenge for psychopharmacologic drug development and contributes to the increasing failure of psychiatric trials. The objective of this meta-regression analysis was to identify potential contributors to placebo response in randomized controlled trials of antipsychotic treatment in schizophrenia. METHOD: The authors extracted trial design and clinical variables from eligible randomized controlled trials (N=50) identified through searches of MEDLINE (1960-2010) and other sources. Standardized mean change (SMC) was used as the effect size measure for placebo response, based on change scores on the Brief Psychiatric Rating Scale or the Positive and Negative Syndrome Scale from baseline to endpoint (2 to 12 weeks). RESULTS: The results suggest significant heterogeneities (Q=387.83, df=49) in the magnitude of placebo response (mean SMC, -0.33, range -1.4 to 0.9) and in study quality. Both placebo SMC and study quality increased over time. Younger age, shorter duration of illness, greater baseline symptom severity, and shorter trial duration were significantly associated with greater placebo response, while country (United States compared with other countries) was not. More study sites, fewer university or Veterans Affairs treatment settings, and a lower percentage of patients assigned to receive placebo were associated with a greater placebo response, but these were not independent of publication year. Study quality affected the variability but not mean levels of placebo response. CONCLUSIONS: This study identified important patient characteristics and trial design factors affecting the level of placebo response and hence the likelihood of detecting efficacy signals in randomized controlled trials. Future studies should test whether controlling these factors improves the detection of an antipsychotic effect.