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Background Patients with schizophrenia (SCZ) display impaired executive functions compared with healthy controls (HCs). Furthermore, unaffected first-degree relatives (FRs) of patients with SCZ independently perform worse executive functions than do HCs. However, few studies have investigated the differences in executive functions assessed among patients with SCZ, FRs, and HCs, and the findings are inconsistent. Methods We investigated diagnostic differences in executive functions, namely (1) numbers of categories achieved (CA), (2) total errors (TE), and (3) percentage of perseverative errors of Nelson types (%PEN), using the Wisconsin card sorting test among patients with SCZ (n = 116), unaffected FRs (n = 62), and HCs (n = 146) at a single institute. Correlations between these executive functions and clinical variables were investigated. Results Significant differences existed in all executive functions among diagnostic groups (CA, F2,319 = 15.5, P = 3.71 × 10–7; TE, F2,319 = 16.2, P = 2.06 × 10–7; and %PEN, F2,319 = 21.3, P = 2.15 × 10–9). Patients with SCZ had fewer CA and more TE and %PEN than those of HCs (CA, Cohen’s d = −0.70, P = 5.49 × 10–8; TE, d = 0.70, P = 5.62 × 10–8; and %PEN, d = 0.82, P = 2.85 × 10−10) and FRs (TE, d = 0.46, P = 3.73 × 10–3 and %PEN, d = 0.38, P = .017). Of the 3 executive functions, CA and %PEN of FRs were intermediately impaired between patients with SCZ and HCs (CA, d = −0.41, P = .011 and %PEN, d = 0.41, P = .012). In contrast, no significant difference in TE existed between FRs and HCs (d = 0.22, P = .18). Although CA and TE were affected by the duration of illness (P &amp;lt; .017), %PEN was not affected by any clinical variable in patients with SCZ (P &amp;gt; .017). Conclusions Executive function, particularly %PEN, could be a useful intermediate phenotype for understanding the genetic mechanisms implicated in SCZ pathophysiology.

Differences in Executive Function Among Patients With Schizophrenia, Their Unaffected First-Degree Relatives, and Healthy Participants