Sex differences in familiality effects on neurocognitive performance in schizophrenia

Monica E. Calkins, Amrita Ray, Ruben C. Gur, Robert Freedman, Michael F. Green, Tiffany A. Greenwood, Gregory A. Light, Keith H. Nuechterlein, Ann Olincy, Allen D. Radant, Larry J. Seidman, Larry J. Siever, Jeremy M. Silverman, William S. Stone, Catherine Sugar, Neal R. Swerdlow, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, David L. BraffLaura C. Lazzeroni, Raquel E. Gur

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Background: Numerous studies have documented that patients with schizophrenia show neurocognitive impairments, which are also heritable in schizophrenia families. In view of these findings, the current investigation tested the hypothesis that neurocognitive performance of schizophrenia probands can predict the neurocognitive performance of their unaffected family members. Methods: Participants (n=1967; schizophrenia=369; first-degree relatives=1072; community comparison subjects=526) in the Consortium on the Genetics of Schizophrenia were administered the Penn Computerized Neurocognitive Battery. Results: Consistent with prior work, probands showed significant neurocognitive impairment, and neurocognitive ability was significantly heritable across domains. On average, unaffected relatives did not differ from community comparison subjects in their neurocognitive performance. However, in six of seven domains, proband scores predicted the performance of their unaffected siblings. Male, but not female, proband performance was predictive of their unaffected relatives' (siblings and mothers) performance, most consistently in face memory and spatial processing. Conclusions: Using a novel approach in which individual probands are paired with their respective unaffected relatives within each family, we found that male proband performance predicted both sister and brother performance, an effect that was most powerfully observed for face memory and spatial processing. Results suggest that the familial transmission of sexually dimorphic neurocognitive domains, in which a particular sex tends to show a performance advantage over the other, may not itself be sex specific in schizophrenia families.

Original languageEnglish
Pages (from-to)976-984
Number of pages9
JournalBiological Psychiatry
Issue number10
StatePublished - 15 May 2013


  • Endophenotype
  • genetics
  • heritability
  • neurocognition
  • schizophrenia
  • sex differences


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