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Neural connectivity biotypes: associations with internalizing problems throughout adolescence
- Rajpreet Chahal, David G. Weissman, Michael N. Hallquist, Richard W. Robins, Paul D. Hastings, Amanda E. Guyer
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- Journal:
- Psychological Medicine / Volume 51 / Issue 16 / December 2021
- Published online by Cambridge University Press:
- 29 May 2020, pp. 2835-2845
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Background
Neurophysiological patterns may distinguish which youth are at risk for the well-documented increase in internalizing symptoms during adolescence. Adolescents with internalizing problems exhibit altered resting-state functional connectivity (RSFC) of brain regions involved in socio-affective processing. Whether connectivity-based biotypes differentiate adolescents’ levels of internalizing problems remains unknown.
MethodSixty-eight adolescents (37 females) reported on their internalizing problems at ages 14, 16, and 18 years. A resting-state functional neuroimaging scan was collected at age 16. Time-series data of 15 internalizing-relevant brain regions were entered into the Subgroup-Group Iterative Multi-Model Estimation program to identify subgroups based on RSFC maps. Associations between internalizing problems and connectivity-based biotypes were tested with regression analyses.
ResultsTwo connectivity-based biotypes were found: a Diffusely-connected biotype (N = 46), with long-range fronto-parietal paths, and a Hyper-connected biotype (N = 22), with paths between subcortical and medial frontal areas (e.g. affective and default-mode network regions). Higher levels of past (age 14) internalizing problems predicted a greater likelihood of belonging to the Hyper-connected biotype at age 16. The Hyper-connected biotype showed higher levels of concurrent problems (age 16) and future (age 18) internalizing problems.
ConclusionsDifferential patterns of RSFC among socio-affective brain regions were predicted by earlier internalizing problems and predicted future internalizing problems in adolescence. Measuring connectivity-based biotypes in adolescence may offer insight into which youth face an elevated risk for internalizing disorders during this critical developmental period.
Tuning of brain–autonomic coupling by prior threat exposure: Implications for internalizing problems in Mexican-origin adolescents
- David G. Weissman, Amanda E. Guyer, Emilio Ferrer, Richard W. Robins, Paul D. Hastings
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- Journal:
- Development and Psychopathology / Volume 31 / Issue 3 / August 2019
- Published online by Cambridge University Press:
- 14 May 2019, pp. 1127-1141
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Exposure to threat increases the risk for internalizing problems in adolescence. Deficits in integrating bodily cues into representations of emotion are thought to contribute to internalizing problems. Given the role of the medial prefrontal cortex in regulating bodily responses and integrating them into representations of emotional states, coordination between activity in the medial prefrontal cortex and autonomic nervous system responses may be influenced by past threat exposure with consequences for the emergence of internalizing problems. A sample of 179 Mexican-origin adolescents (88 female) reported on neighborhood and school crime, peer victimization, and discrimination when they were 10–16 years old. At age 17, participants underwent a functional neuroimaging scan during which they viewed pictures of emotional faces while respiratory sinus arrhythmia (RSA) and skin conductance responses were measured. Adolescents also reported symptoms of internalizing problems. Greater exposure to threats across adolescence was associated with more internalizing problems. Threat exposure was also associated with stronger negative coupling between the ventromedial prefrontal cortex and RSA. Stronger negative ventromedial prefrontal cortex–RSA coupling was associated with fewer internalizing problems. These results suggest the degree of coordinated activity between the brain and parasympathetic nervous system is both enhanced by threat experiences and decreased in adolescents with more internalizing problems.
3520 Neural connectivity mechanisms linking off-time pubertal development and depression risk in adolescence
- Rajpreet Chahal, Scott Marek, Veronika Vilgis, David Weissman, Paul Hastings, Richard Robins, Amanda E. Guyer
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 17-18
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OBJECTIVES/SPECIFIC AIMS: Earlier pubertal timing has been associated with risk for depression, particularly in girls (e.g., Keenan etal., 2014). Evidence suggests pubertal timing in girls also relates to alterations in the microstructural properties of brain white matter tracts in late adolescence (Chahal etal., 2018), and structural connectivity of cingulate and frontal regions (Chahal etal., in prep), though differences in pubertal development in both boys and girls have not been examined in the context of brain functional connectivity (FC). Individual differences in the course of puberty may have enduring effects on functional coupling among brain regions that may contribute to the risk for psychopathology. To address this question, we explored the relation between pubertal timing and tempo with depression symptoms (age 16). Then, we examined whether brain network FC (age 16) associates with pubertal indices and predicts concurrent and later depressive symptoms (age 18). METHODS/STUDY POPULATION: Sixty-eight adolescents (37 females) completed the Mini-Mood and Anxiety Symptom Questionnaire (MASQ; Clark & Watson, 1995) at ages 14-18. Gompertz growth curve modelling of pubertal development (age 10-15; Waves 1-6) was used to estimate pubertal timing and tempo per individual, separately for males and females (e.g., Chahal etal., 2018). Resting-state MRI data (age 16) were parcellated into 264 cortical and subcortical regions to create region-to-region FC matrices based on correlations of time-series. Individual matrices were fed to the GraphVar program (Kruschwitz etal., 2015) to assess the interaction of pubertal timing and pubertal tempo with functional network connectivity using Network-based statistic (NBS; Zalesky etal., 2010). Subnetworks showing alterations in relation to pubertal timing and tempo were then examined in association with concurrent (age 16) symptoms and used to predict future depressive symptoms (age 18). RESULTS/ANTICIPATED RESULTS: In all youth, earlier pubertal timing was associated with higher depressive symptoms at age 16 (p<.018). This association was stronger in girls with slower pubertal tempo (p<.039). Interregional connectivity analyses revealed that the interaction of earlier pubertal timing and slower tempo was associated with lower FC between the left cingulate gyrus and right precuneus (p<.0001), regions implicated in emotion processing (i.e., Affective Processing Network) and self-referential thinking (i.e., Default Mode Network). FC of the three other emotion- and self-referential processing network regions (i.g., left insula, superior parietal lobule, and precuneus) was lower in youth with greater age 16 depressive symptoms (p<.0001). Finally, lower FC of of the left and right inferior parietal lobule predicted greater depressive symptoms at age 18 (p<.0001). In summary, FC of overlapping affective and default mode network areas was related to earlier pubertal timing and higher concurrent and future depressive symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings demonstrate individual differences in pubertal maturation are associated with depressive symptoms and differences in brain connectivity in mid-adolescence. Early pubertal development was associated with greater depression symptoms and lower FC of brain regions involved in emotion regulation and self-referential processing. Further, FC between these regions predicted higher depression symptoms two years later. These neurobiological mechanisms may, in part, underlie the link between off-time pubertal development and the risk for depression. These findings also have important implications for precision psychiatry, as we show that a risk-factor of depression (early pubertal timing) may manifest in developing neurobiology in region-specific ways. Previous network models of depression (e.g., Li etal., 2018) implicated affective network connectivity in sustained negative mood and the default mode/ self-referential network in rumination. Other networks implicated in these past models include the reward network, which may be involved in anhedonia and loss of pleasure. Our study only found associations between affective and self-referential regional connectivity, pubertal maturation, and depression, suggesting that pubertal risk factors may relate more closely with emotion-regulation and self-referential processing deficits.
Lasting associations between early-childhood temperament and late-adolescent reward-circuitry response to peer feedback
- Amanda E. Guyer, Brenda Benson, Victoria R. Choate, Yair Bar-Haim, Koraly Perez-Edgar, Johanna M. Jarcho, Daniel S. Pine, Monique Ernst, Nathan A. Fox, Eric E. Nelson
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- Journal:
- Development and Psychopathology / Volume 26 / Issue 1 / February 2014
- Published online by Cambridge University Press:
- 21 January 2014, pp. 229-243
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Behavioral inhibition, a temperament identifiable in infancy, is associated with heightened withdrawal from social encounters. Prior studies raise particular interest in the striatum, which responds uniquely to monetary gains in behaviorally inhibited children followed into adolescence. Although behavioral manifestations of inhibition are expressed primarily in the social domain, it remains unclear whether observed striatal alterations to monetary incentives also extend to social contexts. In the current study, imaging data were acquired from 39 participants (17 males, 22 females; ages 16–18 years) characterized since infancy on measures of behavioral inhibition. A social evaluation task was used to assess neural response to anticipation and receipt of positive and negative feedback from novel peers, classified by participants as being of high or low interest. As with monetary rewards, striatal response patterns differed during both anticipation and receipt of social reward between behaviorally inhibited and noninhibited adolescents. The current results, when combined with prior findings, suggest that early-life temperament predicts altered striatal response in both social and nonsocial contexts and provide support for continuity between temperament measured in early childhood and neural response to social signals measured in late adolescence and early adulthood.