Emily K. Bell

The Early Psychosis Intervention Center (EPICENTER): development and six-month outcomes of an American first-episode psychosis clinical service

BackgroundThere is growing evidence that specialized clinical services targeted toward individuals early in the course of a psychotic illness may be effective in reducing both the clinical and economic burden associated with these illnesses. Unfortunately, the United States has lagged behind other countries in the delivery of specialized, multi-component care to individuals early in the course of a psychotic illness. A key factor contributing to this lag is the limited available data demonstrating the clinical benefits and cost-effectiveness of early intervention for psychosis among individuals served by the American mental health system. Thus, the goal of this study is to present clinical and cost outcome data with regard to a first-episode psychosis treatment center within the American mental health system: the Early Psychosis Intervention Center (EPICENTER).MethodsSixty-eight consecutively enrolled individuals with first-episode psychosis completed assessments of symptomatology, social functioning, educational/vocational functioning, cognitive functioning, substance use, and service utilization upon enrollment in EPICENTER and after 6 months of EPICENTER care. All participants were provided with access to a multi-component treatment package comprised of cognitive behavioral therapy, family psychoeducation, and metacognitive remediation.ResultsOver the first 6 months of EPICENTER care, participants experienced improvements in symptomatology, social functioning, educational/vocational functioning, cognitive functioning, and substance abuse. The average cost of care during the first 6 months of EPICENTER participation was lower than the average cost during the 6-months prior to joining EPICENTER. These savings occurred despite the additional costs associated with the receipt of EPICENTER care and were driven primarily by reductions in the utilization of inpatient psychiatric services and contacts with the legal system.ConclusionsThe results of our study suggest that multi-component interventions for first-episode psychosis provided in the US mental health system may be both clinically-beneficial and cost-effective. Although additional research is needed, these findings provide preliminary support for the growing delivery of specialized multi-component interventions for first-episode psychosis within the United States.Trial registrationClinicalTrials.gov Identifier: NCT01570972; Date of Trial Registration: November 7, 2011

A randomized controlled trial of cognitive remediation and d-cycloserine for individuals with bipolar disorder.

BackgroundCognitive remediation (CR) has shown significant promise in addressing the cognitive deficits that accompany serious mental illness. However, this intervention does not appear to completely ameliorate the cognitive deficits that accompany these illnesses. D-cycloserine (DCS), an NMDA receptor partial agonist, has been shown to enhance the therapeutic benefits of learning-based psychosocial interventions for psychiatric disorders. Thus, the goal of this study is to examine the utility of combining cognitive remediation and d-cycloserine in the treatment of cognitive deficits among individuals with bipolar disorder.Methods/DesignApproximately forty individuals with bipolar disorder will be recruited to participate in this study. Participants will be randomized to one of two study arms: CR + DCS or CR + placebo. The primary outcome for this study is change in cognitive functioning. We will also examine several secondary outcomes, including the rate of change of cognitive functioning, social functioning, and symptomatology.DiscussionCognitive deficits are a rate-limiting factor in functional recovery among individuals with bipolar disorder. Unfortunately, treatment options for these deficits are limited. The results of the proposed study may reveal a valuable intervention strategy (i.e., CR with concurrent DCS) to improve cognitive functioning among individuals with bipolar disorder. Ultimately, this treatment strategy may prove useful in addressing the cognitive deficits that are ubiquitous across serious mental illnesses.Trial registrationClinicalTrials.gov NCT01934972.

Optimizing psychosocial interventions in first-episode psychosis: current perspectives and future directions

Psychotic-spectrum disorders such as schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features are devastating illnesses accompanied by high levels of morbidity and mortality. Growing evidence suggests that outcomes for individuals with psychotic-spectrum disorders can be meaningfully improved by increasing the quality of mental health care provided to these individuals and reducing the delay between the first onset of psychotic symptoms and the receipt of adequate psychiatric care. More specifically, multicomponent treatment packages that 1) simultaneously target multiple symptomatic and functional needs and 2) are provided as soon as possible following the initial onset of psychotic symptoms appear to have disproportionately positive effects on the course of psychotic-spectrum disorders. Yet, despite the benefit of multicomponent care for first-episode psychosis, clinical and functional outcomes among individuals with first-episode psychosis participating in such services are still suboptimal. Thus, the goal of this review is to highlight putative strategies to improve care for individuals with first-episode psychosis with specific attention to optimizing psychosocial interventions. To address this goal, we highlight four burgeoning areas of research with regard to optimization of psychosocial interventions for first-episode psychosis: 1) reducing the delay in receipt of evidence-based psychosocial treatments; 2) synergistic pairing of psychosocial interventions; 3) personalized delivery of psychosocial interventions; and 4) technological enhancement of psychosocial interventions. Future research on these topics has the potential to optimize the treatment response to evidence-based psychosocial interventions and to enhance the improved (but still suboptimal) treatment outcomes commonly experienced by individuals with first-episode psychosis.

Meta-cognitive skills training enhances computerized cognitive remediation outcomes among individuals with first-episode psychosis.

Meta‐cognitive skills training (MST) is a frequent component of cognitive remediation programmes for individuals with psychosis. However, no study has investigated whether incorporating such activities produces increased clinical benefits compared with computerized cognitive remediation alone.

An uncontrolled trial of multi‐component care for first‐episode psychosis: Effects on social cognition

Growing evidence suggests that specialized, multi‐component treatment programmes produce improvements in numerous outcomes among individuals with first‐episode psychosis. However, these programmes often lack interventions specifically designed to address deficits in social cognition. This raises questions about the effectiveness of such programmes in addressing deficits in social cognition that accompany psychotic disorders. We investigated the effect of participation in a multi‐component treatment programme on social cognition among 71 individuals with first‐episode psychosis. Participants experienced gains in emotion processing, social knowledge, social perception and theory of mind. However, after controlling for multiple comparisons, these improvements were limited to theory of mind and recognition of social cues in low emotion interactions. Although our findings should be interpreted cautiously, they raise the possibility that individuals participating in multi‐component treatment programmes for first‐episode psychosis without interventions specifically targeting social cognition may still experience gains in social cognition.

Activity-regulated cytoskeleton-associated protein predicts response to cognitive remediation among individuals with first-episode psychosis

Fig. 1a. Putative biological pathway for memory and response to cognitive remediation. Numerous proteins associated with risk for psychotic disorders (outlined in red) regulate expression of ARC. As IEGs, both EGR3 and ARC are activated in response to environmental stimuli (red hatched arrows) such as those that trigger learning. This may be via NMDARs or other pathway genes. Maintenance of ARC expression requires EGR3. Dysfunction in ARC, or its upstream regulators may disrupt the normal neurobiological response to stress, setting the stage for symptoms of schizophrenia. Abbreviations: NMDAR N-methyl d-aspartate receptor; NRG2, Neuregulin 1; ERBB4, ErbB4 receptor; NFAT, nuclear factor of activated T cells; EGR3, Early growth response 3; ARC, Activity-regulated cytoskeleton-associated protein. Growing evidence suggests that cognitive remediation (CR) defined by the Cognitive Remediation Experts Workshop as “a behavioral training based intervention that aims to improve cognitive processes with the goal of durability and generalization” -may ameliorate the cognitive deficits that accompany psychotic disorders. However, as a therapy, it is costly and requires specially trained clinicians with expertise and instrumentation. Therefore, the ability to pre-identify individuals who would most likely benefit from this intervention would decrease the time and cost of treatment. Consequently, several studies have investigated possible genetic predictors of response to CR. Focusing primarily on the dopaminergic modulator catechol-O-methyltransferase (COMT), results from these studies are equivocal andmay be confounded by the effects of antipsychotic medication (Bosia et al., 2014). We hypothesized that genes involved in memory and synaptic plasticity may influence the response to CR as these processes are likely stimulated by, and critical for, this therapy. Our prior work has defined an activity-dependent pathway of neuronal proteins that may influence the cognitive symptoms of psychotic illnesses (Huentelman et al., 2015). The proteins in this pathway, beginning with N-methyl D-aspartate receptors and culminating in expression of the immediate early gene activity-regulated cytoskeleton-associated protein (ARC), are essential for memory formation and synaptic plasticity (see Fig. 1a). For the current study, we focused on the role of ARC in moderating response to CR given (i) its association with schizophrenia susceptibility (Huentelman et al., 2015) and (ii) evidence supporting a putative role of ARC in translating environmental learning events (e.g., CR exercises) into changes in neural circuitry (Shepherd and Bear, 2011). This project was approved by the University of Arizona Institutional Review Board. All participants provided informed consent prior to completing study procedures. This study was completed in accordance with the Declaration of Helsinki. Seventy-two individuals with first-episode psychosis were recruited from the Early Psychosis Intervention Center (EPICENTER: Breitborde et al., 2015). Eligibility criteria included: diagnosis of a schizophreniaspectrum disorder or affective disorder with psychotic features, less than 5 years since first onset of psychotic symptoms, being between the ages of 15–35, and no evidence of premorbid intellectual disability. Among our participants, there were 19 women and 53 men, with an average age of 22.72 years and a median duration of psychotic illness of 12.34 months. Participants completed a six-month trial of metacognitive remediation therapy (MCR: Breitborde et al., 2016)—an intervention combining computerized CR exercises and therapist lead metacognitive skills development activities. Cognitive functioning was assessed before and after MCR using the overall cognitive composite score of the MATRICS Consensus Cognitive Battery (MCCB: Nuechterlein et al., 2008).

Social cognition and the course of social functioning in first-episode psychosis

Social functioning deficits greatly affect individuals with psychotic disorders resulting in decreased ability to maintain relationships, jobs and pursuit of educational goals. Deficits in social cognition have been hypothesized to be an important contributor to these deficits in social functioning. In particular, 5 domains of social cognition have been suggested to be relevant in the study of psychotic disorders: (1) attributional style, (2) emotion recognition, (3) social knowledge, (4) social perception and (5) theory of mind. Yet, to date, no study has simultaneously investigated the association between these 5 domains of social cognition and social functioning.