Kambeitz Joseph, Hacker Hannah, Hoheisel Linnea, Buciuman Madalina, Böke Annkathrin, Lichtenstein Theresa, Rosen Marlene, Haas Shalaila, Ruef Anne, Dwyer Dominic, Brambilla Paolo, Bonivento Carolina, Upthegrove Rachel, Wood Stephen, Borgwardt Stefan, Meisenzahl Eva, Ruhrmann Stephan, Salokangas Raimo, Dannlowski Udo, Koutsouleris Nikolaos, Kambeitz-Ilankovic Lana, Lencer Rebekka
Faculty of Medicine and University Hospital University of Cologne, Cologne.
Icahn School of Medicine at Mount Sinai.
Res Sq. 2025 Apr 17:rs.3.rs-6287335. doi: 10.21203/rs.3.rs-6287335/v1.
Patients with psychosis and depression show widespread alterations in brain resting-state functional connectivity (rs-FC), affecting both sensory and higher-order brain regions. In this study, we investigate disruptions in the hierarchical organization of brain functional networks in patients with psychotic and affective disorders. We derived functional brain gradients, low dimensional representations of rs-FC that capture cortical hierarchy, in a large patient sample including clinical high-risk for psychosis (CHR-P) patients, recent-onset psychosis (ROP) patients, recent-onset depression (ROD) patients, and healthy controls (HC). We examined regional alterations, network-level alterations and functional differentiation and their relationship to clinical symptoms. In addition, we linked case-control differences to receptor expression maps to explore underlying neurobiological mechanisms. All patient groups exhibited alterations in the visual-to-sensorimotor gradient, while only ROP patients showed alterations in the association-to-sensory gradient. CHR-P and ROP patients exhibited lower values in the ventral attention network. Additionally, patients combined showed higher values in the somatomotor network, a reduced gradient range and altered between-network dispersion. ROD showed reduced within-network dispersion in the attentional networks and a reduced range. Correlational analysis revealed weak associations of gradient measures with functioning, visual dysfunctions and cognition. Furthermore case-control differences showed associations to receptor expression maps, suggesting the involvement of neurotransmitter systems in these disruptions. Our findings reveal transdiagnostic and disease-specific alterations of hierarchical brain organization. These alterations indicate deficits in functional integration across psychiatric diseases, highlighting the role of attentional and sensory networks in disease processes.
患有精神病和抑郁症的患者大脑静息态功能连接（rs-FC）存在广泛改变，影响感觉和高级脑区。在本研究中，我们调查了患有精神病性和情感性障碍的患者大脑功能网络层次组织的破坏情况。我们在一个大型患者样本中得出了功能性脑梯度，即rs-FC的低维表示，它捕获了皮质层次结构，该样本包括精神病临床高危（CHR-P）患者、近期发病的精神病（ROP）患者、近期发病的抑郁症（ROD）患者和健康对照（HC）。我们检查了区域改变、网络水平改变和功能分化及其与临床症状的关系。此外，我们将病例对照差异与受体表达图谱联系起来，以探索潜在的神经生物学机制。所有患者组在视觉到感觉运动梯度上均表现出改变，而只有ROP患者在联合到感觉梯度上表现出改变。CHR-P和ROP患者在腹侧注意网络中表现出较低的值。此外，合并患者在躯体运动网络中表现出较高的值、梯度范围减小以及网络间离散度改变。ROD在注意网络中表现出网络内离散度降低和范围减小。相关分析揭示了梯度测量与功能、视觉功能障碍和认知之间的弱关联。此外，病例对照差异显示与受体表达图谱有关联，表明神经递质系统参与了这些破坏过程。我们的研究结果揭示了层次化脑组织的跨诊断和疾病特异性改变。这些改变表明精神疾病在功能整合方面存在缺陷，突出了注意和感觉网络在疾病过程中的作用。
