There is a growing body of evidence highlighting the presence of a single general dimension of psychopathology that can account for multiple associations across mental and substance use disorders. However, relatively little evidence has emerged regarding the validity of this model with respect to a range of factors that have been previously implicated across multiple disorders. The current study utilized a cross-sectional population survey of adolescents (n = 2,003) to examine the extent to which broad psychopathology factors account for specific associations between psychopathology and key validators: poor sleep, self-harm, suicidality, risky sexual behavior, and low self-esteem. Confirmatory factor models, latent class models, and factor mixture models were estimated to identify the best structure of psychopathology. Structural equation models were then estimated to examine the broad and specific associations between each psychopathology indicator and the validators. A confirmatory factor model with three lower-order factors, representing internalizing, externalizing, and psychotic-like experiences, and a single higher-order factor evidenced the best fit. The associations between manifest indicators of psychopathology and validators were largely nonspecific. However, significant and large direct effects were found between several pairwise associations. These findings have implications for the identification of potential targets for intervention and/or tailoring of prevention programs.