Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Psychol Med. 2020 Jul;50(10):1672-1679. doi: 10.1017/S0033291719001715. Epub 2019 Jul 31.
The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed.
We employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments.
We observed varying degrees of familial transmission; attention and working memory yielded comparable, significant estimates for adult-onset and community control pedigrees; verbal learning was significant for childhood-onset and community control pedigrees; and facial memory demonstrated significant familial transmission only for childhood-onset schizophrenia. Model-fitting analyses indicated significant differences in familiality between adult- and childhood-onset schizophrenia for attention, working memory, and verbal learning.
By comprehensively assessing a wide range of neurocognitive domains in adult- and childhood-onset schizophrenia families, we provide additional support for specific neurocognitive domains as schizophrenia endophenotypes. Whereas comparable estimates of familial transmission for certain dimensions of cognitive functioning support a shared etiology of adult- and childhood-onset neurocognitive function, observed differences may be taken as preliminary evidence of partially divergent multifactorial architectures.
成年和儿童发病精神分裂症患者的非精神病一级亲属存在神经认知缺陷的聚集,这表明这些缺陷在儿童和成年发病的疾病中可能存在共同的病因。然而,神经生物学异常的表现存在很大的异质性,并且特定认知功能领域的家族传递程度是否存在差异尚未得到系统解决。
我们采用 SOLAR-Eclipse 中实现的方差分量分析来评估经验衍生的代表注意力、工作记忆、言语学习、言语保持和面孔记忆的复合分数的家族传递证据。我们对比了成年和儿童发病精神分裂症家庭以及匹配的社区对照谱系的估计值,并将我们的发现与基于类似神经认知评估的先前报告进行了比较。
我们观察到家族传递程度不同;注意力和工作记忆对于成年发病和社区对照谱系产生了可比的、显著的估计值;言语学习对于儿童发病和社区对照谱系具有显著意义;而面孔记忆仅在儿童发病精神分裂症中表现出显著的家族传递。模型拟合分析表明,注意力、工作记忆和言语学习在成年和儿童发病精神分裂症之间存在家族相似性的显著差异。
通过全面评估成年和儿童发病精神分裂症家庭的广泛神经认知领域,我们为特定的神经认知领域作为精神分裂症的内表型提供了额外的支持。虽然某些认知功能维度的家族传递具有可比性,支持成年和儿童发病神经认知功能的共同病因,但观察到的差异可能被视为部分发散的多因素结构的初步证据。