Researchers Identify 4 Potential Endophenotypes Linked to Schizophrenia

Researchers investigated neurocognitive deficits to discern whether patients with bipolar disorder and schizophrenia shared those deficits with unaffected relatives and to identify putative endophenotypes.

Among several potential endophenotypes commonly linked to schizophrenia, 4 have recently been identified, according to a systematic review published in Schizophrenia Research in July 2019. They are auditory attention, face memory, verbal memory, and emotion processing. There is also notable heterogeneity between studies, underscoring the need for standardized practices in global neurocognitive assessment.

This systematic review included 694 individuals (131 with bipolar disorder, 77 unaffected relatives of individuals with bipolar disorder, 79 with schizophrenia, 159 unaffected relatives of individuals with schizophrenia, and 248 healthy controls) from 5 follow-up studies. These studies were selected from 621 screened articles performed between 1980 and 2018. Inclusion criteria were a year or more of follow up, 2 or more neuropsychological assessments of unaffected relatives, and a lack of high-risk participants. The selected studies had follow-up periods of 4 years, 13 months, 5 years, 10 years, and 5 years, respective to their chronological order. The Newcastle-Ottawa Quality Assessment Scale was used to gauge each study’s quality and risk for bias.

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Verbal memory, emotion processing, face memory, and auditory attention were identified as candidate endophenotypes for schizophrenia. These deficits were observed to persist in family members through longitudinal studies. However, no neurocognitive phenotypes were identified for bipolar disorder in this systematic review, though this is at odds with previous literature and may be due to the small number of eligible studies, as well as inter-study differences in neurocognitive batteries, statistical methods, and sample characteristics.

Significant limitations to this study included heterogeneity between studies and the potential for bias.

Study researchers “highly suggest the endophenotypic nature of persistent neurocognitive dysfunction in [schizophrenia] unaffected relatives, based on longitudinal family studies. The identification of putative neurocognitive endophenotypes by means of this strategy may serve as a tool for early intervention and therapeutic target in [schizophrenia] and according to literature, especially in the case of [bipolar disorder]. Further research is clearly warranted in this area.”


Luperdi SC, Tabarés-Seisdedos R, Livianos L, Vieta E, Cuesta MJ, Balanzá-Martínez V. Neurocognitive endophenotypes in schizophrenia and bipolar disorder: a systematic review of longitudinal family studies [published online July 1, 2019]. Schizophr Res. doi: 10.1016/j.schres.2019.06.014