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. 2023 Jul 17:14:1158569.
doi: 10.3389/fpsyt.2023.1158569. eCollection 2023.

A biomarker discovery framework for childhood anxiety

Affiliations

A biomarker discovery framework for childhood anxiety

William J Bosl et al. Front Psychiatry. .

Abstract

Introduction: Anxiety is the most common manifestation of psychopathology in youth, negatively affecting academic, social, and adaptive functioning and increasing risk for mental health problems into adulthood. Anxiety disorders are diagnosed only after clinical symptoms emerge, potentially missing opportunities to intervene during critical early prodromal periods. In this study, we used a new empirical approach to extracting nonlinear features of the electroencephalogram (EEG), with the goal of discovering differences in brain electrodynamics that distinguish children with anxiety disorders from healthy children. Additionally, we examined whether this approach could distinguish children with externalizing disorders from healthy children and children with anxiety.

Methods: We used a novel supervised tensor factorization method to extract latent factors from repeated multifrequency nonlinear EEG measures in a longitudinal sample of children assessed in infancy and at ages 3, 5, and 7 years of age. We first examined the validity of this method by showing that calendar age is highly correlated with latent EEG complexity factors (r = 0.77). We then computed latent factors separately for distinguishing children with anxiety disorders from healthy controls using a 5-fold cross validation scheme and similarly for distinguishing children with externalizing disorders from healthy controls.

Results: We found that latent factors derived from EEG recordings at age 7 years were required to distinguish children with an anxiety disorder from healthy controls; recordings from infancy, 3 years, or 5 years alone were insufficient. However, recordings from two (5, 7 years) or three (3, 5, 7 years) recordings gave much better results than 7 year recordings alone. Externalizing disorders could be detected using 3- and 5 years EEG data, also giving better results with two or three recordings than any single snapshot. Further, sex assigned at birth was an important covariate that improved accuracy for both disorder groups, and birthweight as a covariate modestly improved accuracy for externalizing disorders. Recordings from infant EEG did not contribute to the classification accuracy for either anxiety or externalizing disorders.

Conclusion: This study suggests that latent factors extracted from EEG recordings in childhood are promising candidate biomarkers for anxiety and for externalizing disorders if chosen at appropriate ages.

Keywords: EEG; biomarkers; childhood anxiety; computational psychiatry; externalizing disorders; nonlinear analysis; tensor analysis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Data processing steps involved in analysis. (1) Multi-frequency decomposition of the signal and computation of nonlinear measures. (2) Latent feature extraction using Supervised Canonical Polyadic (SupCP) algorithm, including EEG measures and covariate data. (3a) Predicting age using regression with latent features. (3b) Classification of anxiety disorder group versus healthy control group, externalizing disorder group versus healthy control group, or anxiety disorder group versus externalizing disorder group.
Figure 2
Figure 2
Scalp view of sensor locations for the standard 10–20 EEG montage.
Figure 3
Figure 3
Tensor organization of multiscale EEG data with additional covariate data shown as a matrix sharing a single axis, participant ID, with the EEG tensor. The developmental time axis is not shown. Latent factors can be used as input to traditional machine learning algorithms. Alternatively, a probabilistic outcome can be computed using the tensor model.
Figure 4
Figure 4
The latent factors that had an individual correlation with age of |r| > 0.2 are displayed here as the most informative factors for age. The right-most column illustrates age correlation with the single latent feature for that row. Age correlation results in Table 3 were computed using all latent features shown here.
Figure 5
Figure 5
Latent factors extracted for distinguishing anxiety disorder group from healthy control group. Covariates were age of initial EEG measurement and sex assigned at birth. The right-most column shows the distribution of weights for the single latent factor in that row. That is, it is a visual illustration of the contribution of that factor. p-values for the factor are also given for each factor alone. The contribution of each nonlinear measure, sensor location, and age to the latent factors can be seen in the bar charts in each column. The dots in the right-most column show separation of diagnostic groups using the single latent variable represented by that row.
Figure 6
Figure 6
Latent factors extracted for distinguishing externalizing disorder group from healthy control group. Covariates were age of initial EEG measurement and sex assigned at birth. The right-most column shows the distribution of weights for the single latent factor in that row. That is, it is a visual illustration of the contribution of that factor. p-values for the factor are also given for each factor alone. The contribution of each nonlinear measure, sensor location, and age to the latent factors can be seen in the bar charts in each column. The dots in the right-most column show separation of diagnostic groups using the single latent variable represented by that row.

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