Project Summary This proposal responds to RFA-MH-18-707, “Confirmatory Efficacy Clinical Trials of Non-Pharmacological Interventions for Mental Disorders (R01).” Adolescents and young adults at clinical high risk (CHR) for psychosis, characterized by recent onset or worsening of attenuated positive symptoms (APS), have a 16%-30% risk of converting to a psychotic disorder in 2 years. In a prior randomized trial in the North American Prodrome Longitudinal Study (NAPLS) network, we showed that family-focused therapy for clinical high-risk persons (FFT- CHR) was more effective than brief family education in (a) improving family (offspring/parent) communication and (b) reducing APS over 6 months, particularly among CHR youth with high baseline scores on a measure of individual risk of psychosis conversion. Both treatments were associated with reductions in young people's perceptions of criticism from parents, which in turn were associated with decreases in APS over 12 months. These findings led us to hypothesize enhanced family communication as a mechanism of action of FFT-CHR. FFT-CHR consists of 18 sessions in 6 months of psychoeducation, communication training, and problem-solving skills training. In the present study conducted in 7 NAPLS sites, we will randomly assign 220 CHR individuals (ages 13-25) and their parent(s) to FFT-CHR or a 6-month Enhanced Care (EC) treatment, consisting of 3 family educational sessions followed by 5 months of individual support and case management. CHR individuals will be interviewed and fill out questionnaires regarding APS (primary outcome) and social functioning (secondary) every 6 months over 18 months. We will examine behavioral targets indicative of improved family relationships: reductions in proportion of critical-conflictual statements and increases in proportion of calm-constructive statements of parents and CHR offspring in laboratory family interactional assessments conducted at baseline and end of treatment (6 months). We will also capture granular changes in targets and outcomes through remote monitoring: CHR participants in both conditions will enroll in a newly developed mobile phone app to facilitate weekly proband ratings of perceived criticism, appraisals of family interactions, and primary and secondary outcomes. We hypothesize that (1) youth/young adults in FFT-CHR will show greater improvements in APS than those in EC in 6 months; (2) improvements in parent and offspring communication by 6 months will be associated with downstream improvements in APS and social functioning over 18 months; and improvements in parent and offspring communication by 6 months will mediate the relationship between treatment condition and changes in primary and secondary outcomes over 18 months. We hypothesize that individuals who are at higher baseline risk of psychosis conversion will show more improvement in targets and primary and secondary outcomes in FFT-CHR than EC, compared to those at lower conversion risk. T...