## 2 Materials and Methods
### Clinical Assessment: Structured Interview (GOASSESS)  
The clinical assessment used in the PNC has been described in detail elsewhere [13,38]. Briefly, psychopathology was assessor-evaluated using a computerized, structured interview (GOASSESS), which was abbreviated and modified from the NIMH Genetic Epidemiology Research Branch Kiddie-SADS [39]. The interview included a timeline of life events, demographics and medical history, psychopathology screen, Children's Global Assessment Scale (C-GAS) [40], and interviewer observations. GOASSESS assessed psychiatric and psychological treatment history and lifetime occurrence of major domains of psychopathology, including psychosis, mood (major depressive episode, manic episode), anxiety (generalized anxiety disorder, separation anxiety disorder, specific phobia, social phobia, panic disorder, agoraphobia, obsessive-compulsive disorder, post-traumatic stress disorder), attention deficit/hyperactivity disorder (ADHD), behavior (oppositional defiant disorder, conduct disorders), eating disorders (anorexia, bulimia), and suicidal thinking and behavior. Computerized algorithms assigned rankings reflecting DSM-IV categories of each psychopathology domain based on endorsement of contributing items by either the proband or collateral (behavioral domains), or by the proband (all other domains). Psychopathology categories were considered significant if sufficient symptoms were endorsed with frequency and duration approximating DSM-IV disorder or episode criteria, accompanied by significant distress or impairment rated \(\geq\) 5 on an 11-point scale. In addition, two screening tools to assess subthreshold psychosis spectrum symptoms were embedded within GOASSESS [38]. First, positive sub-psychotic symptoms were assessed using the PRIME Screen-Revised (PS-R) [41,42], which contains 12 items rated on a 7-point Likert scale (Extremely Disagree to Extremely Agree). PS-R Total Score is the sum of the 12 items. Second, negative/disorganized symptoms were assessed using six assessor-rated subscales of the Scale of Prodromal Symptoms (SOPS) from the Structured Interview for Prodromal Syndromes (SIPS v. 4.0) [43]: Avoiding; Expression of Emotion; Experience of Emotions and Self; Occupational Functioning; Trouble with Focus and Attention; and Disorganized Communication. Youth were categorized into the Psychosis Spectrum (PS) group at baseline if they endorsed any of the following: (a) possible or definite hallucinations or delusions based on K-SADS screen, with duration \(\geq\)1 day, occurring outside the context of substance, illness and medicines, and accompanied by significant impairment or distress (rating \(\geq\) 5); (b) significant subthreshold psychosis symptoms on the PS_R; or (c) significant subthreshold/negative disorganized symptoms on the SOPS (see [PERSON] et al. [38] for full details). The assessments were conducted by bachelor's and master's level assessors who underwent a rigorous 25 h training protocol developed and implemented by the second author, [PERSON] The training included didactic sessions, assigned readings, and supervised pairwise practice. To become certified for independent assessments, assessors had to undergo a standardized procedure requiring observation by a certified clinical observer who rated their proficiency on a 60-item checklist of interview procedures. Additionally,responses coded by the assessor in GOASSESS had to correspond to responses coded by a certified clinical observer. Assessors who did not achieve these standards were required to undergo repeat observation until passing criteria were met. To maintain quality, assessor drift was monitored through periodic review of audio-recordings of real interviews, and re-training and re-certification was conducted at the data collection midpoint. Assessors were assigned a maximum of 10 interviews per week, with the goal of completing 5-7 interviews weekly.