Gray-Matter Morphometry of Internalizing-Symptom Dimensions During Adolescence

Abstract

Understanding the neuroanatomical correlates of internalizing psychopathology during adolescence may shed light on neurodevelopmental processes that make this a critical period for the trajectory of mental illness. However, few studies have simultaneously examined co-occurring and dissociable features of internalizing psychopathology during this formative developmental stage. In the current study, we identify the neuroanatomical correlates of four dimensions of internalizing psychopathology symptoms in adolescents: a common internalizing dimension capturing covariance in symptoms across internalizing disorders, as well as low-positive-affect-specific, anxious-arousal-specific, and anxious-apprehension-specific residuals. Our results suggest that these dimensions are associated with neuroanatomy across much of the brain, including prefrontal and limbic regions implicated in case-control studies and regions supporting visual processing. It is noteworthy that results differed between males and females in regions that are sexually dimorphic in adulthood, and the direction of the effects was largely opposite what has been observed in adults and children.

Sex and age variations in the impact of puberty on cortical thickness and associations with internalizing symptoms and suicidal ideation in early adolescence

“…These null findings may be a function of our sample, who have not yet reached the age for the typical onset of mood disorders and suicidality. Nevertheless, the preliminary signals we were able to identify may be important threads to follow up on in future research in this sample as they progress through adolescence, as many of the ROIs highlighted (e.g., lingual gyrus, isthmus cingulate, precuneus, fusiform gyrus) have been implicated in research on internalizing symptoms, depression, and suicidality in adolescence and adulthood ( Cheng et al, 2018 , Jung et al, 2014 , Ries et al, 2009 , Smolker et al, 2022 , Westlund Schreiner et al, 2019 , Wiglesworth et al, 2021 ).…”

“…Internalizing symptoms have been linked to reduced gray matter volumes in the insula in middle childhood ( Snyder et al, 2017 ) but decreased thinning in the orbital frontal cortex in late childhood ( Pfeifer and Allen, 2021 , Whittle et al, 2020 ). In adolescence, internalizing symptoms are associated with greater fusiform gyrus CT for male and female youth and superior frontal gyrus volumes for male, but not female, youth ( Smolker et al, 2022 ). Further, less surface area of frontal, temporal, and parietal regions ( Gifuni et al, 2021 ), as well as smaller volumes in the right superior temporal gyrus ( Pan et al, 2015 ), are cross-sectionally associated with histories of suicidal behavior in adolescence.…”

Combining dimensional models of internalizing symptoms and repetitive negative thought: Systematic replication, model comparison, and external validation.

“…Both models fit the data well and each factor was associated with diagnostic status for a range of internalizing disorders, including major depressive disorder (MDD) and generalized anxiety disorder (GAD). Follow-up work demonstrated that this factor structure replicates across samples and that the dimensions have distinct neural correlates, providing external validity to each dimension (Banich et al, 2020; Smolker et al, 2022).…”

“…Through confirmatory factor analyses of correlated factors models, Nitschke et al (2001) demonstrated that this expanded model better accounted for variability in symptoms of anxiety than the original model (see first diagram in panel A of Figure 1 for expanded model). Recent research on this model has shifted away from correlated factors models to instead quantify the internalizing symptom dimensions through bifactor and hierarchical parameterizations (e.g., Banich et al, 2020;Smolker et al, 2022;Snyder et al, 2022). These parameterizations are advantageous over correlated factors in their ability to quantify general factors that affect multiple aspects of psychopathology, and, in the case of the bifactor model, also capture dimension-specific factors.…”

“…Recent research on this model has shifted away from correlated factors models to instead quantify the internalizing symptom dimensions through bifactor and hierarchical parameterizations (e.g., Banich et al, 2020; Smolker et al, 2022; Snyder et al, 2022). These parameterizations are advantageous over correlated factors in their ability to quantify general factors that affect multiple aspects of psychopathology, and, in the case of the bifactor model, also capture dimension-specific factors.…”