Doyle A E, Wozniak J, Wilens T E, Henin A, Seidman L J, Petty C, Fried R, Gross L M, Faraone S V, Biederman J
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Child Psychiatry Service, 55 Fruit Street, Boston, MA 02114, USA.
Psychol Med. 2009 Aug;39(8):1253-63. doi: 10.1017/S0033291708004832. Epub 2008 Dec 11.
There is growing evidence for the familiality of pediatric bipolar disorder (BPD) and its association with impairments on measures of processing speed, verbal learning and 'executive' functions. The current study investigated whether these neurocognitive impairments index the familial risk underlying the diagnosis.
Subjects were 170 youth with BPD (mean age 12.3 years), their 118 non-mood-disordered siblings and 79 non-mood-disordered controls. Groups were compared on a battery of neuropsychological tests from the Wechsler Intelligence Scales, the Stroop Color Word Test, the Wisconsin Card Sorting Test (WCST), the Rey-Osterrieth Complex Figure (ROCF), an auditory working memory Continuous Performance Test (CPT) and the California Verbal Learning Test-Children's Version (CVLT-C). Measures were factor analyzed for data reduction purposes. All analyses controlled for age, sex and attention-deficit/hyperactivity disorder (ADHD).
Principal components analyses with a promax rotation yielded three factors reflecting: (1) processing speed/verbal learning, (2) working memory/interference control and (3) abstract problem solving. The CPT working memory measure with interference filtering demands (WM INT) was only administered to subjects aged > or =12 years and was therefore analyzed separately. BPD youth showed impairments versus controls and unaffected relatives on all three factors and on the WM INT. Unaffected relatives exhibited impairments versus controls on the abstract problem-solving factor and the WM INT. They also showed a statistical trend (p=0.07) towards worse performance on the working memory/interference control factor.
Neurocognitive impairments in executive functions may reflect the familial neurobiological risk mechanisms underlying pediatric BPD and may have utility as endophenotypes in molecular genetic studies of the condition.
越来越多的证据表明儿童双相情感障碍(BPD)具有家族聚集性,且与处理速度、言语学习及“执行”功能测量指标的损害有关。本研究调查了这些神经认知损害是否可作为该诊断背后家族风险的指标。
研究对象包括170名患有BPD的青少年(平均年龄12.3岁)、他们118名无情绪障碍的兄弟姐妹以及79名无情绪障碍的对照者。对所有研究对象进行了一系列神经心理学测试,包括韦氏智力量表、斯特鲁普色词测验、威斯康星卡片分类测验(WCST)、雷-奥斯特里赫复杂图形测验(ROCF)、听觉工作记忆连续操作测验(CPT)以及加利福尼亚言语学习测验儿童版(CVLT-C)。为减少数据维度对测量指标进行了因子分析。所有分析均对年龄、性别及注意力缺陷/多动障碍(ADHD)进行了控制。
采用斜交旋转的主成分分析产生了三个因子,分别反映:(1)处理速度/言语学习,(2)工作记忆/干扰控制,(3)抽象问题解决能力。具有干扰过滤要求的CPT工作记忆测量指标(WM INT)仅施测于年龄≥12岁的研究对象,因此单独进行分析。BPD青少年在所有三个因子及WM INT上与对照者及未患病亲属相比均表现出损害。未患病亲属在抽象问题解决因子及WM INT上与对照者相比存在损害。他们在工作记忆/干扰控制因子上也呈现出表现较差的统计学趋势(p = 0.07)。
执行功能的神经认知损害可能反映了儿童BPD潜在的家族神经生物学风险机制,并且在该疾病的分子遗传学研究中作为内表型可能具有实用价值。