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Familial aggregation analysis of cognitive performance in early-onset bipolar disorder

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Abstract

We analysed the familial aggregation (familiality) of cognitive dimensions and explored their role as liability markers for early-onset bipolar disorder (EOBD). The sample comprised 99 subjects from 26 families, each with an offspring diagnosed with EOBD. Four cognitive dimensions were assessed: reasoning skills; attention and working memory; memory; and executive functions. Their familiality was investigated in the total sample and in a subset of healthy relatives. The intra-family resemblance score (IRS), a family-based index of the similarity of cognitive performance among family members, was calculated. Familiality was detected for the attention and working memory (AW) dimension in the total sample (ICC = 0.37, p = 0.0004) and in the subsample of healthy relatives (ICC = 0.37, p = 0.016). The IRS reflected that there are families with similar AW mean scores (either high or low) and families with heterogeneous scores. Families with the most common background for the AW dimension (IRS > 0) were selected and dichotomized in two groups according to the mean family AW score. This allowed differentiating families whose members had similar high scores than those with similar low scores: both patients (t = − 4.82, p = 0.0005) and relatives (t = − 5.04, p < 0.0001) of the two groups differed in their AW scores. AW dimension showed familial aggregation, suggesting its putative role as a familial vulnerability marker for EOBD. The IRS estimation allowed the identification of families with homogeneous scores for this dimension. This represents a first step towards the investigation of the underlying mechanisms of AW dimension and the identification of etiological subgroups.

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Acknowledgements

This study was funded by: (i) Fundación Alicia Koplowitz, (ii) the Instituto de Salud Carlos III through project PI15/01420 (co-funded by the European Regional Development Fund/European Social Fund “Investing in your future”), (iii) the Comissionat per a Universitats i Recerca del DIUE, of the Generalitat de Catalunya regional authorities (2017SGR1577, 2017SGR1271 and 2017SGR881), (iv) an Ajuts de Personal Investigador Predoctoral en Formació grant (APIF-Universitat de Barcelona) awarded to J. Soler, and (vi) a Sara Borrell postdoctoral contract awarded to M. Fatjó-Vilas (CD16/00264).

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The funding sources played no role in the design of the study, the collection, analysis and interpretation of data, or the decision to submit this manuscript for publication. We are also deeply grateful to all participants, whose generosity made this work possible.

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Correspondence to Mar Fatjó-Vilas.

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Ethical approval was obtained from the local research ethics committees. All participants provided written consent after being informed of the study procedures and implications. All procedures were carried out in accordance with the Declaration of Helsinki.

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Soler, J., Lera-Miguel, S., Lázaro, L. et al. Familial aggregation analysis of cognitive performance in early-onset bipolar disorder. Eur Child Adolesc Psychiatry 29, 1705–1716 (2020). https://doi.org/10.1007/s00787-020-01486-8

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