Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies

Burkhouse, Katie L.; Stange, Jonathan P.; Jacobs, Rachel H.; Bhaumik, Runa; Bessette, Katie L.; Peters, Amy T.; Crane, Natania A.; Kreutzer, Kayla A.; Fitzgerald, Kate D.; Monk, Christopher S.; Welsh, Robert C.; Phan, K. Luan; Langenecker, Scott A.

doi:10.1002/da.22864

Cited by 15 publications

(13 citation statements)

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“…the DMN, VAN, and CCN) at age 16, (H2) with one biotype displaying RSFC patterns previously reported in relation to internalizing symptoms, e.g. heightened VAN-DMN and/or lower VAN-CCN (Burkhouse et al, 2019;Geng, Li, Chen, Li, & Gu, 2016;Scheuer et al, 2017). We further hypothesized that connectivity-based biotype would be a biomarker of internalizing problems throughout adolescence, where (H3) prior symptoms (age 14) would predict biotype status at age 16, (H4) current (age 16) problems would be associated with biotypes, and (H5) biotypes would predict future (age 18) internalizing problems (Prenoveau et al, 2011).…”

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confidence: 89%

“…with internalizing psychopathologies, such as depression and anxiety (Burkhouse et al, 2019;Cullen et al, 2014;Roy et al, 2013). Given existing evidence, we expected that internalizing symptoms would be related both to aberrant connectivity within the DMN, VAN, and CCN, as well as differential connectivity between the networks.…”

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confidence: 99%

“…Similarly, reduced RSFC between the amygdala and prefrontal areas has been shown in relation to greater trait anxiety (Greening & Mitchell, 2015). Additionally, lower RSFC connectivity of a 'salience and emotion network' (similar to the VAN) with the CCN from adolescence to adulthood has been found in adolescents with internalizing symptoms (Burkhouse et al, 2019). Given the role of the VAN in emotion processing, and the role of the CCN in cognitive control, lower coupling between these networks may indicate disrupted emotion regulation.…”

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confidence: 99%

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Neural connectivity biotypes: associations with internalizing problems throughout adolescence

et al. 2020

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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. Method Sixty-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. Results Two 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. Conclusions Differential 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.

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confidence: 89%

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confidence: 99%

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confidence: 99%

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Neural connectivity biotypes: associations with internalizing problems throughout adolescence

et al. 2020

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“…At this point, despite a growing recognition that depression is a disorder of brain circuits (Williams, 2017), there are few longitudinal studies of the relation between within‐person changes in network function or structure and depression in adolescents. Although individuals with internalizing psychopathology (e.g., depression and anxiety) have been found to have age‐related alterations in functional network connectivity (Burkhouse et al, 2019), researchers have not yet related longitudinal within‐person changes in connectivity to changes in symptoms of depression over adolescence. Shapero et al (2019) found that abnormalities in CCN and DMN network connectivity predict the onset of depression in adolescence, suggesting that neural anomalies associated with depression are present even before clinical symptoms appear.…”

Section: Emerging Work and Future Directions: Toward A Precision Mentmentioning

confidence: 99%

Research Review: Brain network connectivity and the heterogeneity of depression in adolescence – a precision mental health perspective

Chahal

Gotlib

Guyer

2020

Child Psychology Psychiatry

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Background Adolescence is a period of high risk for the onset of depression, characterized by variability in symptoms, severity, and course. During adolescence, the neurocircuitry implicated in depression continues to mature, suggesting that it is an important period for intervention. Reflecting the recent emergence of ‘precision mental health’ – a person‐centered approach to identifying, preventing, and treating psychopathology – researchers have begun to document associations between heterogeneity in features of depression and individual differences in brain circuitry, most frequently in resting‐state functional connectivity (RSFC). Methods In this review, we present emerging work examining pre‐ and post‐treatment measures of network connectivity in depressed adolescents; these studies reveal potential intervention‐specific neural markers of treatment efficacy. We also review findings from studies examining associations between network connectivity and both types of depressive symptoms and response to treatment in adults, and indicate how this work can be extended to depressed adolescents. Finally, we offer recommendations for research that we believe will advance the science of precision mental health of adolescence. Results Nascent studies suggest that linking RSFC‐based pathophysiological variation with effects of different types of treatment and changes in mood following specific interventions will strengthen predictions of prognosis and treatment response. Studies with larger sample sizes and direct comparisons of treatments are required to determine whether RSFC patterns are reliable neuromarkers of treatment response for depressed adolescents. Although we are not yet at the point of using RSFC to guide clinical decision‐making, findings from research examining the stability and reliability of RSFC point to a favorable future for network‐based clinical phenotyping. Conclusions Delineating the correspondence between specific clinical characteristics of depression (e.g., symptoms, severity, and treatment response) and patterns of network‐based connectivity will facilitate the development of more tailored and effective approaches to the assessment, prevention, and treatment of depression in adolescents.

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“…Furthermore, although we corrected the analyses for age, we were, due to the complexity of the regression models (accounting for familial relationships), unable to take specific neurodevelopmental changes in functional connectivity into account. Previous work indicated changes within resting-state networks across the human lifespan [163] , [164] , [165] , while another study including typically developing individuals and patients with internalizing psychopathologies (age 7-29 years) indicated differential age-related alterations in iFC between the groups [169] . These findings stress the need for incorporating the neurodevelopmental perspective into endophenotype research (cf.…”

Section: Discussionmentioning

confidence: 97%

Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study

et al. 2021

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Background Social anxiety disorder (SAD) is a serious psychiatric condition with a high prevalence, and a typical onset during childhood/adolescence. The condition runs in families, but it is largely unknown which neurobiological characteristics transfer this genetic vulnerability (‘endophenotypes’). Using data from the Leiden Family Lab study on SAD, including two generations of families genetically enriched for SAD, we investigated whether social anxiety (SA) co-segregated with changes in intrinsic functional connectivity (iFC), and examined heritability. Methods Functional MRI data were acquired during resting-state in 109 individuals (56 males; mean age: 31·5, range 9·2-61·5 years). FSL's tool MELODIC was used to perform independent component analysis. Six networks of interest (default mode, dorsal attention, executive control, frontoparietal, limbic and salience) were identified at the group-level and used to generate subject-specific spatial maps. Voxel-wise regression models, with SA-level as predictor and voxel-wise iFC as candidate endophenotypes, were performed to investigate the association with SA, within masks of the networks of interest. Subsequently, heritability was estimated. Findings SA co-segregated with iFC within the dorsal attention network (positive association in left middle frontal gyrus and right postcentral gyrus) and frontoparietal network (positive association within left middle temporal gyrus) (cluster-forming-threshold z >2·3, cluster-corrected extent-threshold p <0·05). Furthermore, iFC of multiple voxels within these clusters was at least moderately heritable. Interpretation These findings provide initial evidence for increased iFC as candidate endophenotype of SAD, particularly within networks involved in attention. These changes might underlie attentional biases commonly present in SAD. Funding Leiden University Research Profile ‘Health, Prevention and the Human Lifecycle’.

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Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies

Cited by 15 publications

References 93 publications

Neural connectivity biotypes: associations with internalizing problems throughout adolescence

Neural connectivity biotypes: associations with internalizing problems throughout adolescence

Research Review: Brain network connectivity and the heterogeneity of depression in adolescence – a precision mental health perspective

Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study

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