Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia. Issue 4 (March 2014)

• Record Type: Journal Article
• Authors: Schultz, C. C.; Mühleisen, T. W.; Nenadic, I.; Koch, K.; Wagner, G.; Schachtzabel, C.; Siedek, F.; Nöthen, M. M.; Rietschel, M.; Deufel, T.; Kiehntopf, M.; Cichon, S.; Reichenbach, J. R.; Sauer, H.; Schlösser, R. G. M.
• Is Part Of: Psychological medicine. Volume 44:Issue 4(2014)
• Page Start: 811
• Page End: 820
• Publication Date: 2014-03
• Subjects: Psychiatry -- Periodicals; Medicine and psychology -- Periodicals; Clinical psychology -- Periodicals; 616.89
• DOI: 10.1017/S0033291713001414
• Languages: English
• ISSNs: 0033-2917

Abstract

<abstract abstract-type="normal"> <title> <x content-type="archive" xml:space="preserve">Abstract</x> </title> <sec id="sec_a1"> <title>Background</title> <p>Recent studies have provided strong evidence that variation in the gene neurocan (<italic>NCAN</italic>, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of <italic>NCAN</italic> variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.</p> </sec> <sec id="sec_a2" sec-type="methods"> <title>Method</title> <p>Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).</p> </sec> <sec id="sec_a3" sec-type="results"> <title>Results</title> <p>In patients, <italic>NCAN</italic> risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (<italic>p</italic> > 0.05). For cortical thickness, there was no significant effect in either patients or controls.</p> </sec> <sec id="sec_a4" sec-type="conclusion"> <title>Conclusions</title> <p>This study is the first to describe an effect of the <italic>NCAN</italic> risk variant on brain structure. Our data show that the <italic>NCAN</italic> risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that <italic>NCAN</italic> is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.</p> </sec> </abstract>