Tehran University of Medical Sciences Iranian Journal of Psychiatry 1735-4587 18 4 2023 09 20 420 428 Mohammad Ali Fallah Zadeh Department of Psychiatry, Roozbeh Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Homayoun Amini Department of Psychiatry, Roozbeh Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Vandad Sharifi Department of Psychiatry, Roozbeh Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mehdi Tehranidoost Research Center for Cognitive and Behavioral Sciences, Tehran University of Medical Sciences, Tehran, Iran Maryam Noroozian Cognitive Neurology and Neuropsychiatry Division, Department of Psychiatry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2022 10 05 2023 05 06 Objective: This study aimed to investigate neurocognitive functioning, quality of life, and global functional performance in Ultra-High Risk (UHR) individuals compared to Familial High-Risk (FHR) individuals for developing schizophrenia. Method: An observational cross-sectional study was conducted using a convenient sampling method at Roozbeh Hospital in Tehran, Iran, from June 2017 to January 2020. The study included 40 UHR individuals based on the Structured Interview for Psychosis Syndrome (SIPS) interview, as well as 34 FHR individuals due to genetic risk. Neurocognitive functioning, quality of life, and global functional performance were assessed by using the Cambridge Automated Neuropsychological Test Battery (CANTAB) and Controlled Oral Word Association Test (COWAT), Quality of Life Scale (QLS), and Global Assessment of Functioning (GAF). Results: UHR individuals for schizophrenia demonstrated significant lower scores in phonemic and semantic verbal fluency (t = 6.218, P < 0.001; t = 4.184, P < 0.001, respectively), more total errors for spatial working memory (t = -5.874, P < 0.001), and fewer problems solved in minimum moves in Stocking of Cambridge (SOC) (t = -2.706, P < 0.01) compared to FHR individuals. Intra-Extra Dimension (IED) did not differ significantly between the two groups. Moreover, the study indicated significant GAF decline (F = 79.257, P < 0.001) and lower total score on the QLS (t = -10.655, P < 0.001) in UHR compared to FHR individuals. Conclusion: It is possible to differentiate UHR individuals from FHR individuals through neurocognitive, quality of life, and global functioning assessment. https://ijps.tums.ac.ir/index.php/ijps/article/view/3397