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Abe, O.

Publications and source records attributed to Abe, O..

3 recordsLinked to original sources

Unsupervised feature computation-based feature selection robustly extracted resting-state functional connectivity patterns related to mental disorders

Research on biomarkers for predicting psychiatric disorders from resting-state functional connectivity (FC) is advancing. While the focus has primarily been on the discriminative performance of biomarkers by machine learning, identification of abnormal FCs in psychiatric disorders has often been treated as a secondary goal. However, it is crucial to investigate the effect size and robustness of the selected FCs because they can be used as potential targets of neurofeedback training or transcranial magnetic stimulation therapy. Here, we incorporated approximately 5,000 runs of resting-state functional magnetic resonance imaging from six datasets, including individuals with three different psychiatric disorders (major depressive disorder [MDD], schizophrenia [SCZ], and autism spectrum disorder [ASD]). We demonstrated that an unsupervised feature-computation-based feature selection method can robustly extract FCs related to psychiatric disorders compared to other conventional supervised feature selection methods. We found that our proposed method robustly extracted FCs with larger effect sizes from the validation dataset compared to different types of feature selection methods based on supervised learning for MDD (Cohens d = 0.40 vs. 0.25), SCZ (0.37 vs. 0.28), and ASD (0.17 vs. 0.16). We found 78, 69, and 81 essential FCs for MDD, SCZ, and ASD, respectively, and these FCs were mainly thalamic and motor network FCs. The current study showed that the unsupervised feature-computation-based feature selection method robustly identified abnormal FCs in psychiatric disorders consistently across datasets. The discovery of such robust FCs will contribute to understanding neural mechanisms as abnormal brain signatures in psychiatric disorders. Furthermore, this finding can aid in developing precise therapeutic interventions, such as neurofeedback training or transcranial magnetic stimulation therapy.

neuroscience↗

Computational Mechanisms of Neuroimaging Biomarkers Uncovered by Multicenter Resting-State fMRI Connectivity Variation Profile

Resting-state functional connectivity (rsFC) is increasingly used to develop biomarkers for psychiatric disorders. Despite progress, development of the reliable and practical FC biomarker remains an unmet goal, particularly one that is clinically predictive at the individual level with generalizability, robustness, and accuracy. In this study, we propose a new approach to profile each connectivity from diverse perspective, encompassing not only disorder-related differences but also disorder-unrelated variations attributed to individual difference, within-subject across-runs, imaging protocol, and scanner factors. By leveraging over 1500 runs of 10-minute resting-state data from 84 traveling-subjects across 29 sites and 900 participants of the case-control study with three psychiatric disorders, the disorder-related and disorder-unrelated FC variations were estimated for each individual FC. Using the FC profile information, we evaluated the effects of the disorder-related and disorder-unrelated variations on the output of the multi-connectivity biomarker trained with ensemble sparse classifiers and generalizable to the multicenter data. Our analysis revealed hierarchical variations in individual functional connectivity, ranging from within-subject across-run variations, individual differences, disease effects, inter-scanner discrepancies, and protocol differences, which were drastically inverted by the sparse machine-learning algorithm. We found this inversion mainly attributed to suppression of both individual difference and within-subject across-runs variations relative to the disorder-related difference by weighted-averaging of the selected FCs and ensemble computing. This comprehensive approach will provide an analytical tool to delineate future directions for developing reliable individual-level biomarkers.

neuroscience↗

Promoter activity-based case-control association study on SLC6A4 highlighting hypermethylation and altered amygdala volume in male patients with schizophrenia

Associations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding gene SLC6A4 and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations of SLC6A4 in schizophrenia (SZ). We examined CpG sites of SLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using three independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site in SLC6A4 in male patients with SZ in all three cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and that in vitro DNA methylation at this CpG site diminished the promoter activity of SLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site in SLC6A4 is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.

genetics↗