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Individual-specific functional connectome biomarkers predict schizophrenia positive symptoms during adolescent brain maturation.

Yun-Shuang Fan | Liang Li | Yue Peng | Haoru Li | Jing Guo | Meiling Li | Siqi Yang | Meng Yao | Jingping Zhao | Hesheng Liu | Wei Liao | Xiaonan Guo | Shaoqiang Han | Qian Cui | Xujun Duan | Yong Xu | Yan Zhang | Huafu Chen
Human brain mapping | 2020

Even with an overarching functional dysconnectivity model of adolescent-onset schizophrenia (AOS), there have been no functional connectome (FC) biomarkers identified for predicting patients' specific symptom domains. Adolescence is a period of dramatic brain maturation, with substantial interindividual variability in brain anatomy. However, existing group-level hypotheses of AOS lack precision in terms of neuroanatomical boundaries. This study aimed to identify individual-specific FC biomarkers associated with schizophrenic symptom manifestation during adolescent brain maturation. We used a reliable individual-level cortical parcellation approach to map functional brain regions in each subject, that were then used to identify FC biomarkers for predicting dimension-specific psychotic symptoms in 30 antipsychotic-naïve first-episode AOS patients (recruited sample of 39). Age-related changes in biomarker expression were compared between these patients and 31 healthy controls. Moreover, 29 antipsychotic-naïve first-episode AOS patients (analyzed sample of 25) were recruited from another center to test the generalizability of the prediction model. Individual-specific FC biomarkers could significantly and better predict AOS positive-dimension symptoms with a relatively stronger generalizability than at the group level. Specifically, positive symptom domains were estimated based on connections between the frontoparietal control network (FPN) and salience network and within FPN. Consistent with the neurodevelopmental hypothesis of schizophrenia, the FPN-SN connection exhibited aberrant age-associated alteration in AOS. The individual-level findings reveal reproducible FPN-based FC biomarkers associated with AOS positive symptom domains, and highlight the importance of accounting for individual variation in the study of adolescent-onset disorders.

Pubmed ID: 33289223

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FreeSurfer (tool)

RRID:SCR_001847

Open source software suite for processing and analyzing human brain MRI images. Used for reconstruction of brain cortical surface from structural MRI data, and overlay of functional MRI data onto reconstructed surface. Contains automatic structural imaging stream for processing cross sectional and longitudinal data. Provides anatomical analysis tools, including: representation of cortical surface between white and gray matter, representation of the pial surface, segmentation of white matter from rest of brain, skull stripping, B1 bias field correction, nonlinear registration of cortical surface of individual with stereotaxic atlas, labeling of regions of cortical surface, statistical analysis of group morphometry differences, and labeling of subcortical brain structures.Operating System: Linux, macOS.

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NIHPD Objective 1 atlases (4.5 - 18.5y) (tool)

RRID:SCR_008794

An unbiased standard magnetic resonance imaging template brain volume for pediatric data from the 4.5 to 18.5y age range. These volumes were created using data from 324 children enrolled in the NIH-funded MRI study of normal brain development (Almli et al., 2007, Evans and Group 2006). Tools for using these atlases can be found in the Software section. To view the atlases online, click on the appropriate JIV2 link in the Download section. You can download templates constructed for different age ranges. For each age range you will get an average T1w, T2w, PDw maps normalized between 0 and 100 and tissue probability maps, with values between 0 and 1. Also each age range includes a binary brain mask.

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