Veddum Lotte, Bliksted Vibeke, Zhou Yuan, Andreassen Anna Krogh, Knudsen Christina Bruun, Greve Aja Neergaard, Steffensen Nanna Lawaetz, Birk Merete, Hemager Nicoline, Brandt Julie Marie, Gregersen Maja, Johnsen Line Korsgaard, Larsen Kit Melissa, Christiaan Baaré William Frans, Madsen Kathrine Skak, Siebner Hartwig Roman, Plessen Kerstin Jessica, Thorup Anne Amalie Elgaard, Østergaard Leif, Nordentoft Merete, Mors Ole, Lund Torben Ellegaard, Dietz Martin
Department of Clinical Medicine, Faculty of Health and Medical Sciences, Aarhus University, Aarhus, Denmark; Psychosis Research Unit, Aarhus University Hospital Skejby-Psychiatry, Aarhus, Denmark; iPSYCH-The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, Aarhus University, Aarhus, Denmark; Psychosis Research Unit, Aarhus University Hospital Skejby-Psychiatry, Aarhus, Denmark; iPSYCH-The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Jan;10(1):68-79. doi: 10.1016/j.bpsc.2024.08.004. Epub 2024 Aug 23.
Schizophrenia and bipolar disorder are characterized by social cognitive impairments, and recent research has identified alterations of the social brain. However, it is unknown whether familial high risk (FHR) of these disorders is associated with neurobiological alterations already present in childhood.
As part of the Danish High Risk and Resilience Study-VIA 11, we examined children at FHR of schizophrenia (n = 121, 50% female) or bipolar disorder (n = 75, 47% female) and population-based control children (PBCs) (n = 128, 48% female). Using functional magnetic resonance imaging and dynamic causal modeling, we investigated brain activation and effective connectivity during the social cognition paradigm from the Human Connectome Project.
We found similar activation of the mentalizing network across groups, including visual area V5, the dorsomedial prefrontal cortex, and the posterior superior temporal sulcus (pSTS). Nonetheless, both FHR groups showed aberrant brain connectivity in the form of increased feedforward connectivity from left V5 to pSTS compared with PBCs. Children at FHR of schizophrenia had reduced intrinsic connectivity in bilateral V5 compared with PBCs, whereas children at FHR of bipolar disorder showed increased reciprocal connectivity between the left dorsomedial prefrontal cortex and the pSTS, increased intrinsic connectivity in the right pSTS, and reduced feedforward connectivity from the right pSTS to the dorsomedial prefrontal cortex compared with PBCs.
Our results provide first-time evidence of aberrant brain connectivity in the mentalizing network of children at FHR of schizophrenia or FHR of bipolar disorder. Longitudinal research is warranted to clarify whether aberrant brain connectivity during mentalizing constitutes an endophenotype associated with the development of a mental disorder later in life.
精神分裂症和双相情感障碍的特征是社会认知缺陷，最近的研究已经确定了社会脑区的改变。然而，这些疾病的家族高风险（FHR）是否与儿童期就已存在的神经生物学改变相关尚不清楚。
作为丹麦高风险与复原力研究-VIA 11的一部分，我们对精神分裂症家族高风险儿童（n = 121，50%为女性）或双相情感障碍家族高风险儿童（n = 75，47%为女性）以及基于人群的对照儿童（PBCs）（n = 128，48%为女性）进行了检查。使用功能磁共振成像和动态因果模型，我们研究了人类连接组计划社会认知范式期间的大脑激活和有效连接性。
我们发现各组间心理理论网络的激活相似，包括视觉区域V5、背内侧前额叶皮层和后颞上沟（pSTS）。尽管如此，与PBCs相比，两个FHR组均表现出异常的脑连接，形式为从左V5到pSTS的前馈连接增加。与PBCs相比，精神分裂症家族高风险儿童双侧V5的内在连接性降低，而双相情感障碍家族高风险儿童表现出左背内侧前额叶皮层与pSTS之间的相互连接增加、右pSTS的内在连接性增加以及与PBCs相比从右pSTS到背内侧前额叶皮层的前馈连接减少。
我们的结果首次证明了精神分裂症家族高风险或双相情感障碍家族高风险儿童心理理论网络中存在异常的脑连接。有必要进行纵向研究，以阐明心理理论过程中的异常脑连接是否构成与生命后期精神障碍发展相关的内表型。
