Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability.

Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age = 9.92 yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals.

SCZ-FH was associated with SCZ-PRS (b = 0.05, FDR-p = 0.02) and subthreshold psychotic symptoms (b = 0.46, FDR-p = 0.01) in European youth, higher CBCL scores (b range = 0.36–0.6, FDR-p < 0.001), and higher odds of multiple internalizing and externalizing disorders (OR = 1.10–1.22, FDR-p < 0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b = −0.43, FDR-p = 0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range = 0.16–0.33, FDR-p < 0.04), and depressive disorders in Admixed American youth (OR = 1.37, FDR-p = 0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences.

SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.

Few studies have examined the underlying factor structure of signs and symptoms occurring before the first psychotic episode. Our objective was to determine whether factors derived from early signs and symptoms are differentially associated with non-affective versus affective psychosis.

A principal components factor analysis was performed on early signs and symptoms reported by 128 individuals with first-episode psychosis. Factor scores were examined for their associations with duration of untreated illness, drug abuse prior to onset of psychosis, and diagnosis (schizophrenia versus affective psychosis).

Of the 27 early signs and symptoms reported by patients, depression and anxiety were the most frequent. Five factors were identified based on these early signs and symptoms: depression, disorganization/mania, positive symptoms, negative symptoms and social withdrawal. Longer duration of untreated illness was associated with higher levels of depression and social withdrawal. Individuals with a history of drug abuse prior to the onset of psychosis scored higher on pre-psychotic depression and negative symptoms. The two mood-related factors, depression and disorganization/mania, distinguished the eventual first-episode diagnosis of affective psychosis from schizophrenia. Individuals with affective psychosis were also more likely to have a ‘mood-related’ sign and symptom as their first psychiatric change than individuals later diagnosed with schizophrenia.

Factors derived from early signs and symptoms reported by a full diagnostic spectrum sample of psychosis can have implications for future diagnostic trajectories. The findings are a step forward in the process of understanding and characterizing clinically important phenomena to be observed prior to the onset of psychosis.