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Aims Young people with attenuated psychotic symptoms (APS), brief intermittent psychosis, and/or genetic risk and functional deterioration are at high risk for developing psychotic disorders. In a prior trial, family-focused therapy for clinical high risk youth (FFT-CHR) was more effective than brief psychoeducation in reducing APS severity over 6 months. This 7-site trial will compare the efficacy of FFT-CHR to a psychoeducational and supportive intervention (enhanced care) on APS and social functioning in CHR individuals over 18 months. Methods Participants (N = 220, ages 13-25 years) with a CHR syndrome will be randomly assigned to FFT-CHR (18 1-h sessions of family psychoeducation and communication/problem-solving skills training) or enhanced care (3 1-h family psychoeducational sessions followed by 5 individual support sessions), both given over 6 months. Participants will rate their weekly progress during treatment using a mobile-enhanced online platform. Family communication will be assessed in a laboratory interactional task at baseline and post-treatment. Independent evaluators will assess APS (primary outcome) and psychosocial functioning (secondary outcome) every 6 months over 18 months. Results We hypothesize that, compared to enhanced care, FFT-CHR will be associated with greater improvements in APS and psychosocial functioning over 18 months. Secondarily, improvements in family communication over 6 months will mediate the relationship between treatment condition and primary and secondary outcomes over 18 months. The effects of FFT-CHR are predicted to be greater in individuals with higher baseline risk for psychosis conversion. Conclusions Results of the trial will inform treatment guidelines for individuals at high risk for psychosis.

Given the chronic and deleterious course of serious mental illness (SMI; schizophrenia and bipolar disorder), significant efforts have been undertaken to improve prediction of SMI and provide treatment for adolescents in the early, putatively prodromal stage of these illnesses. While risk assessments and disorder-specific treatments for adolescents at risk for SMI have shown some efficacy, significant issues remain around disorder-specific treatments for these youth. There is substantial heterogeneity of psychopathology within adolescents at high risk for SMI that leads to many false-positives and varying diagnostic outcomes. As a result, initial treatment focusing on broad symptoms and skills has been proposed in place of disorder-specific treatments. We discuss the rationale for providing an already-developed and empirically supported transdiagnostic treatment for emotional disorders (termed the Unified Protocol) as a first-line staging of treatment for adolescents experiencing early SMI symptoms. Additionally, we outline the open trial we are piloting using this transdiagnostic treatment in adolescents between the ages of 13 – 17 who have begun experiencing distressing yet subsyndromal psychosis or bipolar mood symptoms. Preliminary findings suggest feasibility and acceptability as well as initial efficacy in improving psychiatric symptoms, quality of life, and difficulties regulating emotions. We also present case studies from our open trial. A unified, cognitive-behavioral treatment for early presentations of SMI has important clinical and public health benefits, including streamlining treatment and providing broad skills that are applicable to a wide range of psychopathology.

Introduction Disturbed sleep is a common feature of psychotic disorders that is also present in the clinical high risk (CHR) state. Evidence suggests a potential role of sleep disturbance in symptom progression, yet the interrelationship between sleep and CHR symptoms remains to be determined. To address this knowledge gap, we examined the association between disturbed sleep and CHR symptoms over time. Methods Data were obtained from the North American Prodrome Longitudinal Study (NAPLS)-3 consortium, including 688 CHR individuals and 94 controls (mean age 18.25, 46% female) for whom sleep was tracked prospectively for 8 months. We used Cox regression analyses to investigate whether sleep disturbances predicted conversion to psychosis up to >2 years later. With regressions and cross-lagged panel models, we analyzed longitudinal and bidirectional associations between sleep (the Pittsburgh Sleep Quality Index in conjunction with additional sleep items) and CHR symptoms. We also investigated the independent contribution of individual sleep characteristics on CHR symptom domains separately and explored whether cognitive impairments, stress, depression, and psychotropic medication affected the associations. Results Disturbed sleep at baseline did not predict conversion to psychosis. However, sleep disturbance was strongly correlated with heightened CHR symptoms over time. Depression accounted for half of the association between sleep and symptoms. Importantly, sleep was a significant predictor of CHR symptoms but not vice versa, although bidirectional effect sizes were similar. Discussion The critical role of sleep disturbance in CHR symptom changes suggests that sleep may be a promising intervention target to moderate outcome in the CHR state.

Youths with or at high risk for serious mental illness (SMI; i.e., psychotic or bipolar disorders) have heterogeneous psychiatric symptoms, including significant overlap with more common depressive and anxiety disorders. There are also heterogeneous illness trajectories, as some youth go on to develop chronic and debilitating SMIs while a large proportion have symptoms that remit or remain relatively milder. This chapter presents the rationale for using the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) as a first-line, transdiagnostic, cognitive-behavioral treatment for youth with early SMI symptoms. This treatment is delivered in a group format including parents in an effort to reduce stigma, increase social support, and improve skill acquisition. Preliminary feasibility and efficacy data are presented as well as a case vignette. Recommendations are offered on how to deliver this treatment and troubleshoot common difficulties.

Background 22q11.2 deletion syndrome (22q11DS) is a common recurrent neurogenetic condition associated with elevated risk for developmental neuropsychiatric disorders and intellectual disability. Children and adults with 22q11DS often exhibit marked social impairment as well as neurocognitive deficits, and have elevated rates of both autism spectrum disorder (ASD) and psychosis. However, the relationship between the basic processes of social cognition and cognitive ability has not been well studied in 22q11DS. Here, we examined differences in social cognition in 22q11DS, relative to multiple groups of idiopathic neuropsychiatric disorders, and typically developing healthy controls (HC). Additionally, we examined differences in intellectual functioning and its relationship to social cognitive abilities. Finally, we examined the relationship between social cognitive abilities and real-world social behavior. Methods We examined social cognition and intellectual functioning in 273 participants (mean age = 17.74 ± 5.18% female = 44.3%): 50 with 22q11DS, 49 youth with first episode psychosis (FEP), 48 at clinical high-risk (CHR) for psychosis, 24 participants with ASD, and 102 HC. Social cognition was assessed using The Awareness of Social Inference Test (TASIT), while reciprocal social behavior was assessed via parent/caregiver ratings on the Social Responsiveness Scale (SRS). Participants were also administered the Wechsler Abbreviated Scale of Intelligence, 2nd edition (WASI-II) to assess intellectual functioning. Results The 22q11DS group exhibited significantly lower social cognitive abilities compared to CHR, FEP, and HC groups after controlling for intellectual functioning, but not in comparison to the ASD group. Significant positive correlations were found between social cognition, as measured by the TASIT and IQ across groups. In contrast, no significant relationships were found between TASIT and real-world social behavior (SRS) for any group. Conclusions Our findings indicate social cognitive deficits are more prominent in 22q11DS than idiopathic neuropsychiatric conditions across the age range, even after adjusting for global intellectual function. These results contribute to our understanding of the intellectual and social vulnerabilities of 22q11DS in comparison to idiopathic neuropsychiatric disorders. Our findings of robust associations between intellectual ability and social cognition emphasizes the importance of accounting for neurocognitive deficits in social skills interventions and tailoring these existing treatment models for 22q11DS and other populations with intellectual impairment.

Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.

Individuals with schizophrenia (SZ) consistently show deficits in spatial working memory (WM) and associated atypical patterns of neural activity within key WM regions, including the dorsolateral prefrontal cortex (dlPFC) and parietal cortices. However, little research has focused on adolescent psychosis (AP) and potential age-associated disruptions of WM circuitry that may occur in youth with this severe form of illness. Here we utilized each subject's individual spatial WM capacity to investigate task-based neural dysfunction in 17 patients with AP (16.58 ± 2.60 years old) as compared to 17 typically developing, demographically comparable adolescents (18.07 ± 3.26 years old). AP patients showed lower behavioral performance at higher WM loads and lower overall WM capacity compared to healthy controls. Whole-brain activation analyses revealed greater bilateral precentral and right postcentral activity in controls relative to AP patients, when controlling for individual WM capacity. Seed-based psychophysiological interaction (PPI) analyses revealed significantly greater co-activation between the left dlPFC and left frontal pole in controls relative to AP patients. Significant group-by-age interactions were observed in both whole-brain and PPI analyses, with AP patients showing atypically greater neural activity and stronger coupling between WM task activated brain regions as a function of increasing age. Additionally, AP patients demonstrated positive relationships between right dlPFC neural activity and task performance, but unlike healthy controls, failed to show associations between neural activity and out-of-scanner neurocognitive performance. Collectively, these findings are consistent with atypical WM-related functioning and disrupted developmental processes in youth with AP.

The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12–23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.

Aim Little is known about the role of expressed emotion (EE) in early symptom expression in individuals at clinical high risk (CHR) for psychosis. In patients with established schizophrenia, the effects of EE on clinical outcomes have purportedly varied across racial/ethnic groups, but this has not yet been investigated among CHR patients. Furthermore, studies have traditionally focused upon caregiver levels of EE via interview-based ratings, whereas the literature on patient perceptions of caregiver EE on psychosis symptoms is relatively limited. Methods Linear regression models were conducted to examine the impact of criticism and perceived warmth in the family environment, from the CHR patient's perspective, on positive and negative symptom expression in non-Latino white (NLW; n = 38) and Latino (n = 11) adolescents and young adults at CHR for developing psychosis. Results Analyses examining the sample as a whole demonstrated that perceived levels of maternal criticism were negatively associated with negative CHR symptomatology. Additional analyses indicated that race/ethnicity moderated the relationship between criticism/warmth and clinical symptomatology. We found evidence of a contrasting role of patient perceived criticism and warmth depending upon the patient's race/ethnicity. Conclusion Family processes shown to impact the course of schizophrenia among NLWs may function differently among Latino than NLW patients. These findings have important implications for the development of culturally appropriate interventions and may aid efforts to improve the effectiveness of mental health services for diverse adolescents and young adults at CHR for psychosis. Given the small sample size of this study, analyses should be replicated in a larger study before more definitive conclusions can be made.

Aim There is a wealth of evidence suggesting that patients with schizophrenia tend to respond to life stressors using less effective coping skills, which are in turn related to poor outcome. However, the contribution of coping strategies to outcome in youth at clinical high risk (CHR) for developing psychosis has not been investigated.

ObjectiveLongitudinal studies have begun to clarify the phenotypic characteristics of adolescents and young adults at clinical high risk for psychosis. This 8-site randomized trial examined whether a 6-month program of family psychoeducation was effective in reducing the severity of attenuated positive and negative psychotic symptoms and enhancing functioning among individuals at high risk.MethodAdolescents and young adults (mean age 17.4± 4.1 years) with attenuated positive psychotic symptoms, brief and intermittent psychosis, or genetic risk with functional deterioration were randomly assigned to 18 sessions of family-focused therapy for individuals at clinical high risk (FFT-CHR) in 6 months or 3 sessions of family psychoeducation (enhanced care [EC]). FFT-CHR included psychoeducation about early signs of psychosis, stress management, communication training, and problem-solving skills training, whereas EC focused on symptom prevention. Independent evaluators assessed participants at baseline and 6 months on positive and negative symptoms andsocial-role functioning.ResultsOf 129 participants, 102 (79.1%) were followed up at 6months. Participants in FFT-CHR showed greater improvements in attenuated positive symptoms over 6 months than participants in EC (F1,97= 5.49, p= .02). Negative symptoms improved independently of psychosocial treatments. Changes in psychosocial functioning depended on age: participants more than 19 years of age showed more role improvement inFFT-CHR, whereas participants between 16 and 19 years of age showed more role improvement in EC. The results were independent of concurrent pharmacotherapy.ConclusionInterventions that focus on improving family relationships may have prophylactic efficacy in individuals at high risk for psychosis. Future studies should examine the specificity of effects of family intervention compared to individual therapy of the sameduration and frequency. Clinical trial registration information-Prevention Trial of Family Focused Treatment in Youth at Risk for Psychosis; http://clinicaltrials.gov/; NCT01907282.

Aim: This article outlines the rationale for a family-focused psychoeducational intervention for individuals at risk for psychosis and explains the design of a randomized multisite trial to test its efficacy. Methods: Adolescents and young adults that meet criteria for a psychosis risk syndrome at eight participating North American Prodromal Longitudinal Study sites are randomly assigned to a 6-month, 18-session family-focused treatment for prodromal youth or a 3-session psychoeducational enhanced care control intervention and followed over 1 year. Results: The results will determine whether the use of a family intervention is able to significantly improve functional outcomes, decrease the severity of positive symptoms and possibly prevent the onset of full psychosis, compared with enhanced care alone. Levels of familial criticism at baseline are hypothesized to moderate responses to family intervention. Improvements in knowledge about symptoms, family communication and problem solving will be tested as mediators in the pathways between treatment assignment and clinical or psychosocial outcomes in high-risk youth. Conclusions: The ongoing trial evaluates whether a non-invasive psychosocial approach can significantly enhance functional outcomes and prevent the ultra high risk patients from developing psychosis. The results will provide an important stepping stone in the movement of the field from refining early detection strategies to developing efficacious preventative treatments.

The current study examined the relationship between the family environment and symptoms and functioning over time in a group of adolescents and young adults at clinical high risk for psychosis ( N = 63). The current study compared the ability of interview-based versus self-report ratings of the family environment to predict the severity of prodromal symptoms and functioning over time. The family environmental factors were measured by interviewer ratings of the Camberwell Family Interview (CFI), self-report questionnaires surveying the patient's perceptions of criticism and warmth, and parent reported perceptions of their own level of criticism and warmth. Patients living in a critical family environment, as measured by the CFI at baseline, exhibited significantly worse positive symptoms at a 6-month follow-up, relative to patients living in a low-key family environment. In terms of protective effects, warmth and an optimal level of family involvement interacted such that the two jointly predicted improved functioning at the 6-month follow-up. Overall, both interview-based and self-report ratings of the family environment were predictive of symptoms and functioning at follow-up; however patient's self-report ratings of criticism had stronger predictive power. These results suggest that the family environment should be a specific target of treatment for individuals at risk for psychosis.

Aim: This study investigated the behavioural correlates of caregiver attitudes among parents of youth at risk for psychosis and with recent-onset psychotic symptoms. Methods: Forty adolescents identified as ultra-high-risk (UHR) for psychosis using the Structured Interview for Prodromal Syndromes, and their primary caregivers, participated in the Family Interaction Task (FIT), a 10-minute discussion of meaningful shared experiences that allowed families to demonstrate supportive as well as conflict-engaging behaviour. At the same assessment, caregivers were administered the Camberwell Family Interview (CFI). We examined cross-sectional relationships between these measures, as well as their association with youth symptom severity and functioning at 4-month follow-up. Results: As predicted, caregivers who provided more positive remarks regarding their UHR and recent-onset adolescents during the CFI were also more likely to exhibit constructive behaviour during the FIT. Similarly, CFI critical comments were positively associated with caregivers' conflict-engaging behaviour during the FIT. Parents' positive remarks predicted a decrease in negative symptoms, and parent warmth predicted an increase in social functioning at follow-up assessment. Conclusions: The ability to maintain a constructive attitude and approach towards youth predicted symptomatic and functional improvement, and may be a teachable skill.

Aim: In this study, we investigate the feasibility and acceptability of a 9-month psychoeducational multi-family group (PMFG) intervention for adolescents who are at ultra-high–risk (UHR) for developing psychosis. Methods: The treatment programme was adapted from those previously shown to be effective in patients with established psychotic illness, but emphasizes content relevant to adolescence and to a pre-onset phase of illness. Results: Participants report that psychoeducational presentations are highly useful, they attend the PMFG group sessions regularly and report feeling comfortable in meetings and benefiting from them, and adolescents demonstrate improvement in symptoms and functional outcome. Conclusions: This study was not a randomized controlled trial and multiple interventions were introduced simultaneously; thus, changes in outcome cannot be attributed to the PMFG intervention per se. Nonetheless, these results establish the acceptability of PMFG to adolescents and families, and encourage further research into the potential positive impact of PMFG with this at-risk population.

Objective: This study evaluates longitudinal neuropsychological performance and its association with clinical symptomatology and psychosocial outcome in individuals identified as ultra high risk (UHR) for psychosis. Methods: Thirty-five UHR individuals completed neurocognitive, clinical, and social/role functioning assessments at baseline and, on average, 8.3 months later. Results: UHR subjects showed significant cognitive deficits at baseline and 2 distinct profiles of cognitive change over time. On average, 50% demonstrated improvement in social and role functioning over the follow-up period, while the other half showed either stability or decline in functioning. Functional improvement was associated with improved processing speed and visual memory, as well as improvement in clinical symptoms over the follow-up period. In contrast, patients who did not improve functionally showed stable clinical symptoms and cognitive performance over time. Conclusions: Although the degree of neurocognitive deficit at baseline in UHR patients does not predict psychosocial outcome, the course of neurocognitive change over the first 8 months of follow-up does differentiate patients with good and poor functional outcomes.

Background: Two previous diffusion MRI studies identified widespread excessive extracellular free-water in 2 separate datasets of first-episode schizophrenia patients. Free-water is a diffusion MRI measure that quantifies the fractional volume of water that is free to diffuse, that is, can only be found in extracellular spaces. Additional studies in chronic schizophrenia patients identified very limited or no excessive free-water. While the pathological sources of excessive extracellular free-water are still not known, it is important to understand whether or not such a finding precedes psychosis. To this end, we here investigate free-water abnormalities in prodromal subjects.

Objective: This study investigated whether family focused therapy (FFT-CHR), an 18-session intervention that consisted of psychoeducation and training in communication and problem solving, brought about greater improvements in family communication than enhanced care (EC), a 3-session psychoeducational intervention, among individuals at clinical high risk for developing psychosis. Method: This study was conducted within a randomized controlled trial across 8 sites. We examined 10-min problem-solving discussions at baseline and 6-month reassessment among 66 adolescents and young adults and their parents. Trained coders who were blind to treatment and time of assessment achieved high levels of interrater reliability when evaluating family discussions on categories of calm-constructive and critical-conflictual behavior. Results: Individuals at high risk and their family members who participated in FFT-CHR demonstrated greater improvement from baseline to 6-month reassessment in constructive communication and decreases in conflictual behaviors during family interactions than those in EC. Participants in FFT-CHR showed greater increases from baseline to 6 months in active listening and calm communication and greater decreases in irritability and anger, complaints and criticism, and off-task comments compared to participants in EC. These changes occurred equally in high-risk participants and their family members. Conclusions: A 6-month family skills training treatment can bring about significant improvement in family communication among individuals at high risk for psychosis and their parents. Future studies should examine the association between enhancements in family communication and reduced risk for the onset of psychosis among individuals at high risk. © 2013 American Psychological Association.

This study prospectively examined the relationship between social problem solving behavior exhibited by youths at ultra-high risk for psychosis (UHR) and with recent onset psychotic symptoms and their parents during problem solving discussions, and youths' symptoms and social functioning six months later. Twenty-seven adolescents were administered the Structured Interview for Prodromal Syndromes and the Strauss-Carpenter Social Contact Scale at baseline and follow-up assessment. Primary caregivers participated with youth in a ten minute discussion that was videotaped, transcribed, and coded for how skillful participants were in defining problems, generating solutions, and reaching resolution, as well as how constructive and/or conflictual they were during the interaction. Controlling for social functioning at baseline, adolescents' skillful problem solving and constructive communication, and parents' constructive communication, were associated with youths' enhanced social functioning six months later. Controlling for symptom severity at baseline, we found that there was a positive association between adolescents' conflictual communications at baseline and an increase in positive symptoms six months later. Taken together, findings from this study provide support for further research into the possibility that specific family interventions, such as problem solving and communication skills training, may improve the functional prognosis of at-risk youth, especially in terms of their social functioning.

Gender differences have been widely observed in the clinical presentation, psychosocial functioning and course of illness in first episode and chronic patients suffering from schizophrenia. However, little is known about gender differences in the psychosis prodrome. This study investigated gender differences in symptoms, functioning and social support in individuals at ultra-high-risk for developing a psychotic disorder. Sixty-eight ultra-high-risk patients were assessed at baseline, and twenty-seven returned for follow-up assessments approximately six and twelve months later. Clinical symptoms and functioning were assessed by clinical interview; social support was measured using a self-report questionnaire. There were no gender differences in demographic variables, symptoms or functioning at baseline. Males were found to have significantly higher levels of negative symptoms and marginally lower levels of functioning when baseline and follow-up time points were considered collectively. Additionally, females reported higher levels of social support at baseline. Differences in negative symptoms were found to mediate differences in functioning between male and female patients. This study suggests that gender based differences in symptom presentation and functional outcome may predate conversion to psychosis. Follow-up studies should examine the relationship between symptoms, functioning and social support in this population.

Introduction: Research on prediction and prevention of schizophrenia has increasingly focused on prodromal (prepsychosis) social and role dysfunction as developmentally early, stable, and treatment-resistant illness components. In this report, 2 new measures, Global Functioning: Social and Global Functioning: Role, are presented, along with preliminary findings about psychometric properties and course of social and role (academic/work) functioning in the prodromal phase of psychosis. Methods: Subjects included 69 participants from the Recognition and Prevention program and 52 from the Center for the Assessment and Prevention of Prodromal States. Ages ranged from 12 to 29 years, and all met criteria for Attenuated Positive Symptom syndrome. Retrospective (past year) and baseline data are reported for all 121 prodromal subjects and for 44 normal controls (NCs). Prospective follow-up data are reported for a subsample of patients reevaluated at both 6 and 12 months (N = 44). Results: For both scales, inter-rater reliability was high, and preliminary data supported construct validity. Relative to NCs, prodromal individuals displayed impaired social and role functioning at baseline. Analyses of change over time indicated that role functioning declined over the year before ascertainment and improved over 12-month follow-up, presumably with treatment. Social impairment, by contrast, was constant across time and predicted later psychosis (P = .002). Discussion: Using 2 new global measures, social functioning was found to be a stable trait, unchanged by treatment, with considerable potential to be a marker of schizophrenia. Role functioning, by contrast, may be a more direct barometer of clinical change and may be responsive to treatment and environmental change.