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Cognitive performances across individuals at high genetic risk for schizophrenia, high genetic risk for bipolar disorder, and low genetic risks: a combined polygenic risk score approach

Published online by Cambridge University Press:  16 August 2022

Kazutaka Ohi Open the ORCID record for Kazutaka Ohi [Opens in a new window] ,
Daisuke Nishizawa ,
Shunsuke Sugiyama ,
Kentaro Takai ,
Daisuke Fujikane ,
Ayumi Kuramitsu ,
Junko Hasegawa ,
Midori Soda ,
Kiyoyuki Kitaichi  and
Ryota Hashimoto
...Show all authors
Kazutaka Ohi*
Affiliation:
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan Department of General Internal Medicine, Kanazawa Medical University, Ishikawa, Japan
Daisuke Nishizawa
Affiliation:
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Shunsuke Sugiyama
Affiliation:
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
Kentaro Takai
Affiliation:
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
Daisuke Fujikane
Affiliation:
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
Ayumi Kuramitsu
Affiliation:
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
Junko Hasegawa
Affiliation:
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Midori Soda
Affiliation:
Laboratory of Pharmaceutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan
Kiyoyuki Kitaichi
Affiliation:
Laboratory of Pharmaceutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan
Ryota Hashimoto
Affiliation:
Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
Kazutaka Ikeda
Affiliation:
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Toshiki Shioiri
Affiliation:
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
*
Author for correspondence: Kazutaka Ohi, E-mail: k_ohi@gifu-u.ac.jp
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Abstract

Background

Individuals with schizophrenia (SCZ) and bipolar disorder (BD) display cognitive impairments, but the impairments in those with SCZ are more prominent, supported by genetic overlap between SCZ and cognitive impairments. However, it remains unclear whether cognitive performances differ between individuals at high and low genetic risks for SCZ or BD.

Methods

Using the latest Psychiatric Genomics Consortium (PGC) data, we calculated PGC3 SCZ-, PGC3 BD-, and SCZ v. BD polygenic risk scores (PRSs) in 173 SCZ patients, 70 unaffected first-degree relatives (FRs) and 196 healthy controls (HCs). Based on combinations of three PRS deciles, individuals in the genetic SCZ, genetic BD and low genetic risk groups were extracted. Cognitive performance was assessed by the Brief Assessment of Cognition in Schizophrenia.

Results

SCZ-, BD-, SCZ v. BD-PRSs were associated with case–control status (R2 = 0.020–0.061), and SCZ-PRS was associated with relative–control status (R2 = 0.023). Furthermore, individuals in the highest decile for SCZ PRSs had elevated BD-PRSs [odds ratio (OR) = 6.33] and SCZ v. BD-PRSs (OR = 1.86) compared with those in the lowest decile. Of the three genetic risk groups, the low genetic risk group contained more HCs, whereas the genetic BD and SCZ groups contained more SCZ patients (p < 0.05). SCZ patients had widespread cognitive impairments, and FRs had cognitive impairments that were between those of SCZ patients and HCs (p < 0.05). Cognitive differences between HCs in the low genetic risk group and SCZ patients in the genetic BD or genetic SCZ groups were more prominent (Cohen's d > −0.20) than those between HCs and SCZ patients in the no genetic risk group. Furthermore, SCZ patients in the genetic SCZ group displayed lower scores in verbal fluency and attention than those in the genetic BD group (d > −0.20).

Conclusions

Our findings suggest that cognitive impairments in SCZ are partially mediated through genetic loadings for SCZ but not BD.

Keywords

Bipolar disordercognitive functiongenome-wide association studieshigh genetic riskpolygenic risk score decilesschizophrenia
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 10 , July 2023 , pp. 4454 - 4463
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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