Bannai Deepthi, Reuter Martin, Hegde Rachal, Hoang Dung, Adhan Iniya, Gandu Swetha, Pong Sovannarath, Raymond Nick, Zeng Victor, Chung Yoonho, He George, Sun Daqiang, van Erp Theo G M, Addington Jean, Bearden Carrie E, Cadenhead Kristin, Cornblatt Barbara, Mathalon Daniel H, McGlashan Thomas, Jeffries Clark, Stone William, Tsuang Ming, Walker Elaine, Woods Scott W, Cannon Tyrone D, Perkins Diana, Keshavan Matcheri, Lizano Paulo
Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA.
Brain Behav Immun. 2024 Mar;117:70-79. doi: 10.1016/j.bbi.2023.12.021. Epub 2023 Dec 31.
BACKGROUND: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. METHODS: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. RESULTS: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1β (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. CONCLUSIONS: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.
背景：脉络丛（ChP）增大存在于首发和慢性精神病中，但在精神病发作前是否发生增大尚不清楚。本研究调查了精神病临床高危（CHR）个体的ChP体积是否增大，以及这些变化是否与临床、神经解剖学和血浆分析物相关。 方法：使用北美前驱期纵向研究2（NAPLS2）的临床和神经影像学数据进行分析。招募了509名参与者（169名对照，340名CHR）。随访2年后确定转化状态，有36名精神病转化者。从基线扫描中手动分割侧脑室脉络丛。31名对照和53名CHR的子样本有血浆分析物和神经影像学数据。 结果：与对照相比，CHR（d = 0.23，p = 0.017）和未转化者（d = 0.22，p = 0.03）的ChP体积更大，但转化者并非如此。在CHR中，更大的ChP体积与较低的皮质（r = -0.22，p < 0.001）、皮质下灰质（r = -0.21，p < 0.001）和总白质体积（r = -0.28，p < 0.001）相关，以及与更大的侧脑室体积（r = 0.63，p < 0.001）相关。在CHR中，更大的ChP体积与功能上与侧脑室脉络丛相关的标志物相关[CCL1（r = -0.30，p = 0.035），ICAM1（r = 0.33，p = 0.02）]，转化者[IL1β（r = 0.66，p = 0.004）]和未转化者[BMP6（r = -0.96，p < 0.001），CALB1（r = -0.98，p < 0.001），ICAM1（r = 0.80，p = a003），SELE（r = 0.59，p = 0.026），SHBG（r = 0.99，p < 0.001），TNFRSF10C（r = 0.78，p = 0.001）]。 结论：与对照相比，CHR和未转化者的ChP体积明显更大。脉络丛增大与神经解剖学改变以及功能上与脉络丛相关的分析物标志物相关。这些发现表明脉络丛可能是CHR中的一个关键重要生物标志物。
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