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Neuron. 2014 Mar 5;81(5):1203-1213. doi: 10.1016/j.neuron.2014.01.010. Epub 2014 Feb 13.

Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity.

Author information

1
Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland. Electronic address: angela.heck@unibas.ch.
2
Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
3
Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
4
Department of Psychiatry, Technical University of Munich, 85748 Munich, Germany.
5
Department of Psychiatry, University of Bonn, 53105 Bonn, Germany; DZNE, German Center for Neurogenerative Diseases, 53105 Bonn, Germany.
6
Department of Primary Medical Care, Center of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
7
Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland.
8
Institute of General Practice, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
9
Institute of Social Medicine, Occupational Health and Public Health, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
10
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
11
Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
12
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
13
Central Institute of Mental Health, 68159 Mannheim, Germany.
14
Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Transfaculty Research Platform, University of Basel, CH-4012 Basel, Switzerland.
15
Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland; Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland; Transfaculty Research Platform, University of Basel, CH-4012 Basel, Switzerland. Electronic address: andreas.papas@unibas.ch.

Abstract

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 = 2,824) and in a large schizophrenia case-control sample (n = 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 schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set 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.

PMID:
24529980
PMCID:
PMC4205276
DOI:
10.1016/j.neuron.2014.01.010
[Indexed for MEDLINE]
Free PMC Article

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