Converging Genetic and Functional Brain Imaging Evidence Links Neuronal Excitability to Working Memory, Psychiatric Disease, and Brain Activity

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• 作者：Angela Heck¹ ; ² ; ¹⁵ ; ^{angela.heck@unibas.ch" class="auth_mail} ; Matthias Fastenrath¹ ; ³ ; ¹⁵ ; Sandra Ackermann¹ ; Bianca Auschra¹ ; Horst Bickel⁴ ; David Coynel¹ ; ³ ; Leo Gschwind¹ ; ³ ; Frank Jessen⁵ ; ⁶ ; Hanna Kaduszkiewicz⁷ ; Wolfgang Maier⁵ ; ⁶ ; Annette Milnik¹ ; ² ; Michael Pentzek⁸ ; Steffi G. Riedel-Heller⁹ ; Stephan Ripke¹⁰ ; Klara Spalek³ ; Patrick Sullivan¹¹ ; Christian Vogler¹ ; ² ; Michael Wagner⁵ ; ⁶ ; Siegfried Weyerer¹² ; Steffen Wolfsgruber⁵ ; ⁶ ; Dominique J.-F. de Quervain² ; ³ ; ¹⁴ ; Andreas Papassotiropoulos¹ ; ² ; ¹³ ; ¹⁴ ; ^{andreas.papas@unibas.ch" class="auth_mail}
• 刊名：Neuron
• 出版年：5 March, 2014
• 年：2014
• 卷：81
• 期：5
• 页码：1203-1213
• 全文大小：948 K

文摘

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Summary

Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n聽= 2,824) and in a large schizophrenia case-control sample (n聽= 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to聽schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set聽also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.