Longitudinal Relationships Among Activity in Attention Redirection Neural Circuitry and Symptom Severity in Youth

Abstract

Background Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort. Methods Forty-one youth completed two study visits (mean=21.3 months). Elastic-net regression (Multiple response Gaussian family) identified emotional regulation neural circuitry that changed in association with changes in depression, mania, anxiety, affect lability, and positive mood and energy dysregulation, accounting for clinical and demographic variables. Results Non-zero coefficients between change in the above symptom measures and change in activity over the inter-scan interval were identified in right amygdala and left ventrolateral prefrontal cortex. Differing patterns of neural activity change were associated with changes in each of the above symptoms over time. Specifically, from Scan1 to Scan2, worsening affective lability and depression severity were associated with increased right amygdala and left ventrolateral prefrontal cortical activity. Worsening anxiety and positive mood and energy dysregulation were associated with decreased right amygdala and increased left ventrolateral prefrontal cortical activity. Worsening mania was associated with increased right amygdala and decreased left ventrolateral prefrontal cortical activity. These changes in neural activity between scans accounted for 13.6% of the variance; that is 25% of the total explained variance (39.6%) in these measures. Conclusions Distinct neural mechanisms underlie changes in different mood and anxiety symptoms overtime.

Longitudinal Associations Between Sleep Patterns and Psychiatric Symptom Severity in High-Risk and Community Comparison Youth

“…As such, our five psychiatric symptom outcome measures (KMRS, KDRS, CALS, SCARED, DBDRS) were considered as a multivariate outcome rather than as separate univariate outcomes. As in a prior report from our group, 35 all five psychiatric symptoms were considered as outcomes simultaneously and predictors had to be associated with all five outcomes. Correlations among the psychiatric symptom measures at baseline further supports the use of a multivariate outcome ( r values 0.29–0.56).…”

“…Predictors of change in the five psychiatric symptom outcome measures were selected by a single multivariate penalized least squares (lasso) regression implemented in the R GLMNET package. 35,38 Lasso is a modified form of least squares regression that penalizes complex models with a regularization parameter ( λ ); the regularization parameter shrinks coefficients toward zero and eliminates unimportant terms entirely. 38–41 This approach has two key advantages over traditional least squares regression: (1) it allows one to consider many predictors without the issue of multiple comparisons and (2) mitigates issues regarding predictor inter-correlation in the feature selection process.…”

“…38–41 This approach has two key advantages over traditional least squares regression: (1) it allows one to consider many predictors without the issue of multiple comparisons and (2) mitigates issues regarding predictor inter-correlation in the feature selection process. 35,38 Ten-fold cross-validation identifies the optimal penalty term (λ) that minimizes mean cross-validated error (Lambda.min). Lambda.1se corresponds to the λ that is 1 standard error from the lambda.min and provides the most regularized (parsimonious) model; 41 lambda.1se was used for predictor selection.…”

“…To assess variance explained by the lasso-selected predictors, pseudo-r-squared was computed using the loglikelihood from leave-one-out MANOVA regression model analyses in R. 35 A fixed-effects MANOVA model was used for the main analyses, as a multivariate mixed-effect model accounting for within-family correlation indicated that family membership accounted for a small portion of the total random effect variance and yielded no improvement in model fit relative to the fixed effects MANOVA in a loglikelihood ratio test ( p >0.1). See Supplemental Methods (available online) for more detailed rationale.…”

Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication

“…This may be related to the effects of psychotropic medications on precuneus function 70–72 , as LAMS youth were more likely to be medicated. The absence of an association between future factor scores and amygdala activity may suggest that changes in amygdala activity, rather than baseline amygdala activity, are related to future symptom measures 73 . Further studies are needed to understand the above relationships.…”