Association between negative symptoms and health-related quality of life and functional outcomes in persons with schizophrenia: A systematic review

BACKGROUND: Negative symptoms in schizophrenia (SCZ) are core phenomenological characteristics known to affect health-related quality of life (HRQoL) and functioning. This systematic review aims to synthesize extant literature to evaluate/elucidate the effect of negative symptoms on HRQoL and functional outcomes in persons with SCZ, as well as to better understand the association between HRQoL and functional outcomes. METHOD: A systematic search was conducted from inception to July 24, 2025, using Pubmed, MedLine, Embase, AMED, PsychInfo, and Scopus. All studies were independently screened by three reviewers (A.C., A.L., T.M.). Primary studies reporting on the association between negative symptoms, HRQoL, and/or functional outcomes in persons with SCZ were included. RESULTS: We included 68 relevant studies. Most studies were observational and cross-sectional, while others employed case-control, before-after without control, or randomized controlled trial designs. A consistent, small, negative correlation was observed between the presence and severity of negative symptoms and HRQoL (r = -0.67 to 0.69), as well as functional outcomes (r = -0.85 to 0.63. A slight positive association was found between functional outcomes and HRQoL (r = -0.63 to 0.58). CONCLUSION: Our findings underscore the significant impact of negative symptoms on critical patient-reported outcomes, including HRQoL and functional outcomes. Notwithstanding their clinical importance, there is limited research on negative symptoms, and more research is needed on treatments that address negative symptoms directly, emphasizing the urgent need for targeted therapeutic development.