Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Biol Psychiatry. 2010 Dec 15;68(12):1120-5. doi: 10.1016/j.biopsych.2010.07.036. Epub 2010 Oct 15.
Working memory (WM) is the ability to retain task relevant information. This ability is important for a wide range of cognitive tasks, and WM deficits are a central cognitive impairment in neurodevelopment disorders such as attention-deficit/hyperactivity disorder (ADHD). Although WM capacity is known to be highly heritable, most genes involved remain unidentified.
Single nucleotide polymorphisms in genes previously associated with cognitive functions or ADHD were selected for genotyping. Associations of these with WM tasks were investigated in a community sample of 330 children and young adults. One single nucleotide polymorphisms was also investigated in an independent sample of 88 4-year-old children. Furthermore, association between brain structure and activity, as measured by magnetic resonance imaging techniques, and single nucleotide polymorphisms alleles were estimated in 88 participants.
Genotype at rs363039, located in the gene coding for synaptosomal-associated protein, 25 kDa (SNAP25) was associated to WM capacity in both samples. Associations in the community sample were also found with measures of other cognitive functions. In addition, this polymorphism affected the gray matter and brain activity in the posterior cingulate cortex, an area included in the so-called default mode network previously correlated to regulation of attention and hypothesized to be implicated in ADHD.
A novel gene-brain-behavior network was identified in which a genotype located in SNAP25 affects WM and has age-dependent effects on both brain structure and brain activity. Identifying such networks could be a key to better understanding cognitive development as well as some of its disorders.
工作记忆(WM)是保留与任务相关信息的能力。这种能力对广泛的认知任务很重要,WM 缺陷是神经发育障碍(如注意缺陷多动障碍(ADHD))的核心认知障碍。尽管 WM 能力的遗传性很高,但大多数涉及的基因仍未被确定。
选择先前与认知功能或 ADHD 相关的基因中的单核苷酸多态性进行基因分型。在 330 名儿童和年轻人的社区样本中研究了这些单核苷酸多态性与 WM 任务的关联。在 88 名 4 岁儿童的独立样本中还研究了一个单核苷酸多态性。此外,还估计了 88 名参与者的磁共振成像技术测量的大脑结构和活动与单核苷酸多态性等位基因之间的关联。
位于编码突触相关蛋白 25kDa(SNAP25)的基因中的 rs363039 基因型与两个样本中的 WM 能力相关。在社区样本中,还发现了与其他认知功能测量值的关联。此外,这种多态性影响了后扣带皮层的灰质和大脑活动,后扣带皮层是所谓的默认模式网络的一部分,该网络与注意力的调节相关,并且假设与 ADHD 有关。
确定了一个新的基因-大脑-行为网络,其中位于 SNAP25 的基因型影响 WM,并对大脑结构和大脑活动具有年龄依赖性影响。识别此类网络可能是更好地理解认知发育及其一些障碍的关键。