Recreational cannabis use over time in individuals at clinical high risk for psychosis: Lack of associations with symptom, neurocognitive, functioning, and treatment patterns.

Recreational cannabis use has recently gained considerable interest as an environmental risk factor that triggers the onset of psychosis. To date, however, the evidence that cannabis is associated with negative outcomes in individuals at clinical high risk (CHR) for psychosis is inconsistent. The present study tracked cannabis usage over a 2-year period and examined its associations with clinical and neurocognitive outcomes, along with medication rates. CHR youth who continuously used cannabis had higher neurocognition and social functioning over time, and decreased medication usage, relative to non-users. Surprisingly, clinical symptoms improved over time despite the medication decreases.

The association between mental health stigma and face emotion recognition in individuals at risk for psychosis.

Self-stigma has been associated with reduced accuracy of face emotion recognition in individuals at clinical high risk for psychosis (CHR). Stigma may also relate to slowing of performance during cognitive tasks for which a negative stereotype is relevant. This study aimed to investigate the association of mental illness stigma with face emotion recognition among CHR individuals. Participants were 143 CHR individuals identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Face emotion recognition was assessed using the Penn Emotion Recognition Task (ER-40). Stigma was assessed using discrimination, stereotype awareness, and stereotype agreement subscales of the Mental Health Attitudes Interview for CHR. We tested associations of ER-40 accuracy and response times with these stigma variables, including the role of clinical and demographic factors. Racial/ethnic minoritized participants had higher attenuated positive symptoms than non-minoritized participants. Longer ER-40 response times were correlated with greater stereotype agreement (r=.17, p=.045) and discrimination (r=.22, p=.012). A regression model predicting ER-40 response times revealed an interaction of stereotype agreement with minoritized status (p=.008), with slower response times for minoritized participants as stereotype agreement increased. Greater disorganized symptoms and male gender also predicted longer response times. ER-40 accuracy was not associated with stigma. Overall, minoritized CHR individuals with greater internalized stigma took longer to identify face emotions. Future research is needed to assess whether slower response times are specific to social cues, and if internalized stigma interferes with performance in real-world social situations. Reducing stigma may be an important target for interventions that aim to improve social skills.

Emotional and stigma-related experiences relative to being told one is at risk for psychosis.

OBJECTIVE: Despite the appeal of early intervention in psychosis, there is concern that identifying youth as having high psychosis risk (PR) may trigger stigma. This study employed a pre-post design to measure change in PR participants' emotions about PR upon being told of their PR status and according to whether this was the first time receiving this information. METHODS: Participants (n = 54) identified as at PR via structured interview rated their emotions about PR before and after being told they were at PR. Qualitative analyses explored the valence of participant reflections on being given this information. RESULTS: Participants reported significantly less negative emotion after being told of their PR status (p < .001), regardless of whether they were hearing this for the first time (p = .72). There was no change in positive emotions or the predominant belief that they should keep their PR status private. Most participants commented positively about the process of feedback but negatively about its impact on their self-perceptions and/or expectations of others' perceptions of them. CONCLUSION: This is the first study to collect pre-post data related to being told one is at PR and to examine quantitative and qualitative responses across and within individuals. For a majority of participants, clinical feedback stimulated negative stereotypes even as it relieved some distress. To actively address internalized stigma, clinicians providing feedback to PR youth must attend to the positive and negative impacts on how youth think about themselves as well as how they feel.

Predicting psychosis risk using a specific measure of cognitive control: a 12-month longitudinal study.

BACKGROUND: Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up. METHODS: Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models. RESULTS: Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups. CONCLUSIONS: These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.

Baseline psychopathology and relationship to longitudinal functional outcome in attenuated and early first episode psychosis.

BACKGROUND: As efforts intensify to intervene early among those at risk for psychosis, examination of the relationship between presenting psychopathology and long-term functional outcome may guide treatment decision-making and offer a means to prevent or reduce chronic disability. METHODS: Data were collected through the Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP), a multisite national trial testing the efficacy of an early intervention for youth at risk of developing psychosis. Participants were followed prospectively and completed comprehensive evaluations at 6, 12, and 24 months, including the Structured Interview for Prodromal Syndromes (SIPS) and the Global Social and Role Functioning Scales. The present analyses included 327 participants and examined the relationships between baseline symptoms and longitudinal global social and role functioning using a linear mixed modeling approach. RESULTS: Higher baseline negative symptoms and deteriorated thought process predicted worse social and role functioning in the follow-up period. The effect of negative symptoms on social functioning, however, was moderated by positive symptoms, and the relationship between positive symptoms and social functioning changed over time. Baseline positive symptoms, distress, and level of symptom severity were not predictors of either social or role functioning. CONCLUSIONS: Baseline negative symptoms and thought disorder appear to predict functional outcome for up to two years among adolescents and young adults at risk for psychosis. Developing effective interventions to target these symptoms may be critical to promote functional recovery among those experiencing attenuated symptoms or a first episode of psychosis.

Impact of "psychosis risk" identification: Examining predictors of how youth view themselves.

BACKGROUND: Identifying young people as at clinical high-risk (CHR) for psychosis affords opportunities for intervention to possibly prevent psychosis onset. Yet such CHR identification could plausibly increase stigma. We do not know whether these youth already perceive themselves to be at psychosis-risk (PR) or how their being told they are at PR might impact how they think about themselves. METHODS: 148 CHR youth were asked about labels they had been given by others (labeling by others) or with which they personally identified (self-labeling). They were then asked which had the greatest impact on how they thought about themselves. We evaluated whether being told vs. thinking they were at PR had stronger effects. FINDINGS: The majority identified nonpsychotic disorders rather than PR labels as having the greatest impact on sense of self (67.6% vs. 27.7%). However, participants who identified themselves as at PR had an 8.8 (95% CI = 2.0-39.1) increase in the odds of the PR label having the greatest impact (p < 0.01). Additionally, having been told by others that they were at PR was associated with a 4.0 increase in odds (95% CI = 1.1-15.0) that the PR label had the most impact (p < 0.05). INTERPRETATION: Nonpsychotic disorder labels appear to have a greater impact on CHR youth than psychosis-risk labels. However, thinking they are at PR, and, secondarily, being told they are at PR, appears to increase the relative impact of the PR label. Understanding self- and other-labeling may be important to how young people think of themselves, and may inform early intervention strategies.

Sensory characteristics of youth at clinical high risk for psychosis.

AIM: To identify and compare the sensory characteristics of young people at clinical high risk (CHR) for psychosis to those of peers at clinical low risk (CLR), and to national normative data. CHR and CLR participants were recruited from 6 US regions. METHOD: A descriptive cohort design was used to analyse baseline data collected as part of the Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP). Raw scores on the Adolescent/Adult Sensory Profile (AASP) were analysed for 205 young people with CHR and 87 with CLR in 2 age groups: 12 to 17 years (N = 203) and 18 to 25 years (N = 89). ANOVA procedures were used to determine whether differences in AASP scores existed across CLR, CHR, and normative groups by age group. RESULTS: CHR participants differed significantly from the normative group for all 4 AASP quadrant scores (Low Registration, Sensory Seeking, Sensory Sensitivity and Sensory Avoiding) in both age groups. CLR participants were similar to norms, except for Sensory Seeking scores that were significantly lower than norms in both age ranges. CONCLUSION: Young people with CHR demonstrate active avoidance, heightened sensitivity, reduced seeking, and reduced registration of sensations in everyday life compared to typical peers. This pattern of differences may be a valuable marker for identifying individuals who are at high risk for developing a psychotic illness, and may also inform interventions designed to prevent or minimize the illness process and accompanying dysfunction.

From the psychosis prodrome to the first-episode of psychosis: No evidence of a cognitive decline.

Cognitive deficits have an important role in the neurodevelopment of schizophrenia and other psychotic disorders. However, there is a continuing debate as to whether cognitive impairments in the psychosis prodrome are stable predictors of eventual psychosis or undergo a decline due to the onset of psychosis. In the present study, to determine how cognition changes as illness emerges, we examined baseline neurocognitive performance in a large sample of helping-seeking youth ranging in clinical state from low-risk for psychosis through individuals at clinical high-risk (CHR) for illness to early first-episode patients (EFEP). At baseline, the MATRICS Cognitive Consensus battery was administered to 322 individuals (205 CHRs, 28 EFEPs, and 89 help-seeking controls, HSC) that were part of the larger Early Detection, Intervention and Prevention of Psychosis Program study. CHR individuals were further divided into those who did (CHR-T; n = 12, 6.8%) and did not (CHR-NT, n = 163) convert to psychosis over follow-up (Mean = 99.20 weeks, SD = 21.54). ANCOVAs revealed that there were significant overall group differences (CHR, EFEP, HSC) in processing speed, verbal learning, and overall neurocognition, relative to healthy controls (CNTL). In addition, the CHR-NTs performed similarly to the HSC group, with mild to moderate cognitive deficits relative to the CTRL group. The CHR-Ts mirrored the EFEP group, with large deficits in processing speed, working memory, attention/vigilance, and verbal learning (>1 SD below CNTLs). Interestingly, only verbal learning impairments predicted transition to psychosis, when adjusting for age, education, symptoms, antipsychotic medication, and neurocognitive performance in the other domains. Our findings suggest that large neurocognitive deficits are present prior to illness onset and represent vulnerability markers for psychosis. The results of this study further reinforce that verbal learning should be specifically targeted for preventive intervention for psychosis.

Factor analysis of the Scale of Prodromal Symptoms: data from the Early Detection and Intervention for the Prevention of Psychosis Program.

AIM: The Scale of Prodromal Symptoms (SOPS) was developed to identify individuals experiencing early signs of psychosis, a critical first step towards early intervention. Preliminary dimension reduction analyses suggested that psychosis-risk symptoms may deviate from the traditional symptom structure of schizophrenia, but findings have been inconsistent. This study investigated the phenomenology of psychosis risk symptoms in a large sample from a multi-site, national study using rigorous factor analysis procedure. METHODS: Participants were 334 help-seeking youth (age: 17.0 ± 3.3) from the Early Detection and Intervention for the Prevention of Psychosis Program, consisting of 203 participants at clinically higher risk (sum of P scores ≥ 7), 87 with clinically lower risk (sum of P scores < 7) and 44 in very early first-episode psychosis (<30 days of positive symptoms). Baseline SOPS data were subjected to principal axis factoring (PAF), estimating factors based on shared variance, with Oblimin rotation. RESULTS: PAF yielded four latent factors explaining 36.1% of total variance: positive symptoms; distress; negative symptoms; and deteriorated thought process. They showed reasonable internal consistency and good convergence validity, and were not orthogonal. CONCLUSIONS: The empirical factors of the SOPS showed similarities and notable differences compared with the existing SOPS structure. Regrouping the symptoms based on the empirical symptom dimensions may improve the diagnostic validity of the SOPS. Relative prominence of the factors and symptom frequency support early identification strategies focusing on positive symptoms and distress. Future investigation of long-term functional implications of these symptom factors may further inform intervention strategies.

Personalized Prediction of Psychosis: External Validation of the NAPLS-2 Psychosis Risk Calculator With the EDIPPP Project.

OBJECTIVE: As part of the second phase of the North American Prodrome Longitudinal Study (NAPLS-2), Cannon and colleagues report, concurrently with the present article, on a risk calculator for the individualized prediction of a psychotic disorder in a 2-year period. The present study represents an external validation of the NAPLS-2 psychosis risk calculator using an independent sample of patients at clinical high risk for psychosis collected as part of the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP). METHOD: Of the total EDIPPP sample of 210 subjects rated as being at clinical high risk based on the Structured Interview for Prodromal Syndromes, 176 had at least one follow-up assessment and were included in the construction of a new prediction model with six predictor variables in the NAPLS-2 psychosis risk calculator (unusual thoughts and suspiciousness, symbol coding test performance, verbal learning test performance, decline in social functioning, baseline age, and family history). Discrimination performance was assessed with the area under the receiver operating characteristic curve (AUC). The NAPLS-2 risk calculator was then used to generate a psychosis risk estimate for each case in the external validation sample. RESULTS: The external validation model showed good discrimination, with an AUC of 0.790 (95% CI=0.644-0.937). In addition, the personalized risk generated by the risk calculator provided a solid estimation of the actual conversion outcome in the validation sample. CONCLUSIONS: Two independent samples of clinical high-risk patients converge to validate the NAPLS-2 psychosis risk calculator. This prediction calculator represents a meaningful step toward early intervention and the personalized treatment of psychotic disorders.

Family Interventions for Schizophrenia and the Psychoses: A Review.

Family psychoeducation as a treatment for schizophrenia was developed 40 years ago almost simultaneously and independently by investigators who at the time were not family therapists. Although the original goal was to decrease high expressed emotion as a means of preventing relapse, later variations have gone beyond to focus on social and role functioning and family well-being. Explicitly disavowing the earlier assumptions that family pathology caused relapse and deterioration, family psychoeducation seeks to engage family members as more sophisticated partners, complementing interventions by clinicians with specialized interactions and coping skills that counter the neurologic deficits inherent to the disorder. It has proved to be one of the most consistently effective treatments available. Reports on outcome studies now number more than 100, while meta-analyses put relapse rate reduction at 50-60% over treatment as usual. The most recent application in first episode and prodromal psychosis, combined with other evidence-based interventions, is yielding perhaps the most promising results yet achieved-substantial return of functioning and avoidance of psychosis altogether. Reviewed here are its scientific, theoretical, and clinical sources, a description of the most commonly applied version-the multifamily group format, selected clinical trials spanning those four decades, international and ethnic adaptations, and studies on mechanisms of efficacy.

Early Detection, Intervention and Prevention of Psychosis Program: Community Outreach and Early Identification at Six U.S. Sites.

OBJECTIVE: This study assessed the effects of a community outreach and education model implemented as part of the Early Detection, Intervention and Prevention of Psychosis Program (EDIPPP), a national multisite study in six U.S. regions. METHODS: EDIPPP's model was designed to generate rapid referrals of youths at clinical high risk of psychosis by creating a network of professionals and community members trained to identify signs of early psychosis. Qualitative and quantitative data were gathered through an evaluation of outreach efforts at five sites over a two-year period and through interviews with staff at all six sites. All outreach activities to groups (educational, medical, and mental health professionals; community groups; media; youth and parent groups; and multicultural communities) were counted for the six sites to determine correlations with total referrals and enrollments. RESULTS: During the study period (May 2007-May 2010), 848 formal presentations were made to 22,840 attendees and 145 informal presentations were made to 11,528 attendees at all six sites. These presentations led to 1,652 phone referrals. A total of 520 (31%) of these individuals were offered in-person orientation, and 392 (75%) of those were assessed for eligibility. A total of 337 individuals (86% of those assessed) met criteria for assignment to the EDIPPP study. CONCLUSIONS: EDIPPP's outreach and education model demonstrated the effectiveness of following a protocol-defined outreach strategy combined with flexibility to reach culturally diverse audiences or initially inaccessible systems. All EDIPPP sites yielded appropriate referrals of youths at risk of psychosis.

Clinical and functional outcomes after 2 years in the early detection and intervention for the prevention of psychosis multisite effectiveness trial.

OBJECTIVE: To test effectiveness of the Early Detection, Intervention, and Prevention of Psychosis Program in preventing the onset of severe psychosis and improving functioning in a national sample of at-risk youth. METHODS: In a risk-based allocation study design, 337 youth (age 12-25) at risk of psychosis were assigned to treatment groups based on severity of positive symptoms. Those at clinically higher risk (CHR) or having an early first episode of psychosis (EFEP) were assigned to receive Family-aided Assertive Community Treatment (FACT); those at clinically lower risk (CLR) were assigned to receive community care. Between-groups differences on outcome variables were adjusted statistically according to regression-discontinuity procedures and evaluated using the Global Test Procedure that combined all symptom and functional measures. RESULTS: A total of 337 young people (mean age: 16.6) were assigned to the treatment group (CHR + EFEP, n = 250) or comparison group (CLR, n = 87). On the primary variable, positive symptoms, after 2 years FACT, were superior to community care (2 df, p < .0001) for both CHR (p = .0034) and EFEP (p < .0001) subgroups. Rates of conversion (6.3% CHR vs 2.3% CLR) and first negative event (25% CHR vs 22% CLR) were low but did not differ. FACT was superior in the Global Test (p = .0007; p = .024 for CHR and p = .0002 for EFEP, vs CLR) and in improvement in participation in work and school (p = .025). CONCLUSION: FACT is effective in improving positive, negative, disorganized and general symptoms, Global Assessment of Functioning, work and school participation and global outcome in youth at risk for, or experiencing very early, psychosis.

Reduction in incidence of hospitalizations for psychotic episodes through early identification and intervention.

OBJECTIVE: This study examined whether the incidence of hospitalization for psychosis was reduced by a communitywide system of early identification and intervention to prevent onset of psychosis. METHODS: The Portland Identification and Early Referral program (PIER) was initiated in 2001. Youths and young adults ages 12-35 were identified by professionals in a wide variety of educational, health, and mental health settings. PIER program staff assessed, confirmed risk of psychosis, and provided treatment for 24 months to eligible and consenting young people (N=148). The monthly rate of first hospital admission for psychosis was the outcome measure for efficacy of identification and intervention. Admission rates before and after the program began accepting referrals were compared, both in the experimental area (Greater Portland) and in aggregated urban areas of Maine (control areas). Autoregressive integrated moving-average (ARIMA) models were used to assess the effect. RESULTS: On the basis of ARIMA models, the rate of first hospital admission for psychosis decreased significantly by 26% (95% confidence interval [CI]=-64% to -11%) in the Greater Portland area. The rate increased by 8% (CI=-5% to 36%) in the control areas. Taking into account the increase in the control areas, the actual percentage reduction in Greater Portland during the intervention period was 34% (26% plus 8%). The reduction in admissions was largest for individuals with nonaffective nonschizophrenic psychosis. CONCLUSIONS: PIER has demonstrated that populationwide early identification is feasible. Preventive intervention can reduce rates of initial hospitalizations for psychosis in a midsized city.

Change in neuropsychological functioning over one year in youth at clinical high risk for psychosis.

Schizophrenia and related psychotic disorders are associated with significant neuropsychological (NP) impairments. Yet the onset and developmental evolution of these impairments remains incompletely characterized. This study examined NP functioning over one year in a sample of youth at clinical high risk (CHR) for psychosis participating in a treatment study. We assessed functioning across six cognitive domains at two time points in a sample of 53 CHR and 32 healthy comparison (HC) subjects. Linear regression of HC one-year scores was used to predict one-year performance for CHR from baseline scores and relevant demographic variables. We used raw scores and MANOVAs of the standardized residuals to test for progressive impairment over time. NP functioning of CHR at one year fell significantly below predicted levels. Effects were largest and most consistent for a failure of normative improvement on tests of executive function. CHR who reached the highest positive symptom rating (6, severe and psychotic) on the Structured Interview of Prodromal Syndromes after the baseline assessment (n = 10/53) demonstrated a particularly large (d = -1.89), although non-significant, discrepancy between observed and predicted one-year verbal memory test performance. Findings suggest that, although much of the cognitive impairment associated with psychosis is present prior to the full expression of the psychotic syndrome, some progressive NP impairments may accompany risk for psychosis and be greatest for those who develop psychotic level symptoms.

Prevention of the first episode of psychosis.

Long a desired goal but increasingly a focus of research on clinical practice, prevention of psychosis has emerged as one of the most promising and effective areas of investigational interest and effort in psychiatry. Spurred by long-term studies that have associated outcome with duration of untreated psychosis, current research is focused on improving the accuracy of prediction based on clinical and neurocognitive measures and on refining treatments of the earliest symptoms of the psychoses. Both efforts are bearing success, although there remains ambiguity as to the most effective preventive interventions. This article reviews the leading studies of, and remaining issues for, this important enterprise.

Multifamily group psychoeducation and cognitive remediation for first-episode psychosis: a randomized controlled trial.

BACKGROUND: Multifamily group psychoeducation (MFG) has been shown to reduce relapse rates among individuals with first-episode psychosis. However, given the cognitive demands associated with participating in this intervention (e.g., learning and applying a structured problem-solving activity), the cognitive deficits that accompany psychotic disorders may limit the ability of certain individuals to benefit from this intervention. Thus, the goal of this study is to examine whether individuals with first-episode psychosis who participate simultaneously in MFG and cognitive remediation--an intervention shown to improve cognitive functioning among individuals with psychotic disorders--will be less likely to experience a relapse than individuals who participate in MFG alone. METHODS/DESIGN: Forty individuals with first-episode psychosis and their caregiving relative will be recruited to participate in this study. Individuals with first-episode psychosis will be randomized to one of two conditions: (i) MFG with concurrent participation in cognitive remediation or (ii) MFG alone. The primary outcome for this study is relapse of psychotic symptoms. We will also examine secondary outcomes among both individuals with first-episode psychosis (i.e., social and vocational functioning, health-related quality of life, service utilization, independent living status, and cognitive functioning) and their caregiving relatives (i.e., caregiver burden, anxiety, and depression) DISCUSSION: Cognitive remediation offers the possibility of ameliorating a specific deficit (i.e., deficits in cognitive functioning) that often accompanies psychotic symptoms and may restrict the magnitude of the clinical benefits derived from MFG. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT01196286.

Neuropsychological profiles in individuals at clinical high risk for psychosis: relationship to psychosis and intelligence.

BACKGROUND: Characterizing neuropsychological (NP) functioning of individuals at clinical high risk (CHR) for psychosis may be useful for prediction of psychosis and understanding functional outcome. The degree to which NP impairments are associated with general cognitive ability and/or later emergence of full psychosis in CHR samples requires study with well-matched controls. METHODS: We assessed NP functioning across eight cognitive domains in a sample of 73 CHR youth, 13 of whom developed psychotic-level symptoms after baseline assessment, and 34 healthy comparison (HC) subjects. Groups were matched on age, sex, ethnicity, handedness, subject and parent grade attainment, and median family income, and were comparable on WRAT-3 Reading, an estimate of premorbid IQ. Profile analysis was used to examine group differences and the role of IQ in profile shape. RESULTS: The CHR sample demonstrated a significant difference in overall magnitude of NP impairment but only a small and nearly significant difference in profile shape, primarily due to a large impairment in olfactory identification. Individuals who subsequently developed psychotic-level symptoms demonstrated large impairments in verbal IQ, verbal memory and olfactory identification comparable in magnitude to first episode samples. CONCLUSIONS: CHR status may be associated with moderate generalized cognitive impairments marked by some degree of selective impairment in olfaction and verbal memory. Impairments were greatest in those who later developed psychotic symptoms. Future study of olfaction in CHR samples may enhance early detection and specification of neurodevelopmental mechanisms of risk.