Adolescent Brain Development and Depression: A Case for the Importance of Connectivity of the Anterior Cingulate Cortex

Overview

Journal Neurosci Biobehav Rev

Specialties Neurology
Psychology
Social Sciences

Date 2016 Jul 28

PMID 27461914

Citations 53

Authors

Sarah D Lichenstein

Timothy Verstynen

Erika E Forbes

Affiliations

Soon will be listed here.

Abstract

We propose that structural and functional connectivity of the anterior cingulate cortex (ACC) represents a critical component of adolescent developmental psychopathology. We hypothesize that connectivity of the ACC, a hub for integrating cognitive, affective, and social information to guide self-regulation across domains, supports adaptive development of self-regulation during adolescence and that, conversely, disrupted maturation of ACC connectivity contributes to the development of depression. To integrate findings on typical development, we report results of a meta-analysis of diffusion imaging findings of typical adolescent development of the cingulum and anterior thalamic radiations, the tracts most relevant to ACC connectivity, and provide a critical review of the literature on ACC functional connectivity. Finally, we review the evidence for altered structural and functional connectivity in adolescents with depression. Although the evidence for our claim is persuasive, a more comprehensive understanding of the ACC's role depends upon future investigations with sophisticated modeling of networks, prospective and longitudinal designs, and examination of structure-function associations.

Citing Articles

Resting-state fMRI reveals altered functional connectivity associated with resilience and susceptibility to chronic social defeat stress in mouse brain.

Lupinsky D, Nasseef M, Parent C, Craig K, Diorio J, Zhang T Mol Psychiatry. 2025; .

PMID: 39984680 DOI: 10.1038/s41380-025-02897-2.

Protocol for a nested case-control study: identifying neuroimaging biomarkers for the progression of subclinical depression and qi-stagnation constitution to major depressive disorder in adolescents.

Wang J, Zhang C, Zhang Y, Liu Y, Zhang J, Fang X Front Psychiatry. 2025; 15:1516846.

PMID: 39906680 PMC: 11790624. DOI: 10.3389/fpsyt.2024.1516846.

The amplitude of low-frequency fluctuations is correlated with birth trauma in patients with postpartum post-traumatic stress disorder.

Chen C, Li B, Chai L, Liu K, Zhang S Transl Psychiatry. 2024; 14(1):332.

PMID: 39143051 PMC: 11324796. DOI: 10.1038/s41398-024-03018-3.

Family and parenting factors are associated with emotion regulation neural function in early adolescent girls with elevated internalizing symptoms.

Lin S, Pozzi E, Kehoe C, Havighurst S, Schwartz O, Yap M Eur Child Adolesc Psychiatry. 2024; 33(12):4381-4391.

PMID: 38832959 PMC: 11618192. DOI: 10.1007/s00787-024-02481-z.

A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease.

Chen Y, Peng H, Zhuang K, Xie W, Li C, Chen M iScience. 2024; 27(5):109778.

PMID: 38746665 PMC: 11091694. DOI: 10.1016/j.isci.2024.109778.

References

Jarbo K, Verstynen T . Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum. J Neurosci. 2015; 35(9):3865-78. PMC: 4461697. DOI: 10.1523/JNEUROSCI.2636-14.2015. View

Blakemore S, Mills K . Is adolescence a sensitive period for sociocultural processing?. Annu Rev Psychol. 2013; 65:187-207. DOI: 10.1146/annurev-psych-010213-115202. View

Spati J, Hanggi J, Doerig N, Ernst J, Sambataro F, Brakowski J . Prefrontal thinning affects functional connectivity and regional homogeneity of the anterior cingulate cortex in depression. Neuropsychopharmacology. 2015; 40(7):1640-8. PMC: 4915268. DOI: 10.1038/npp.2015.8. View

Huang H, Fan X, Williamson D, Rao U . White matter changes in healthy adolescents at familial risk for unipolar depression: a diffusion tensor imaging study. Neuropsychopharmacology. 2010; 36(3):684-91. PMC: 3036948. DOI: 10.1038/npp.2010.199. View

Whelan R, Watts R, Orr C, Althoff R, Artiges E, Banaschewski T . Neuropsychosocial profiles of current and future adolescent alcohol misusers. Nature. 2014; 512(7513):185-9. PMC: 4486207. DOI: 10.1038/nature13402. View

Cullen K, Gee D, Klimes-Dougan B, Gabbay V, Hulvershorn L, Mueller B . A preliminary study of functional connectivity in comorbid adolescent depression. Neurosci Lett. 2009; 460(3):227-31. PMC: 2713606. DOI: 10.1016/j.neulet.2009.05.022. View

Geier C . Adolescent cognitive control and reward processing: implications for risk taking and substance use. Horm Behav. 2013; 64(2):333-42. DOI: 10.1016/j.yhbeh.2013.02.008. View

Perrin J, Merz S, Bennett D, Currie J, Steele D, Reid I . Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder. Proc Natl Acad Sci U S A. 2012; 109(14):5464-8. PMC: 3325678. DOI: 10.1073/pnas.1117206109. View

Strikwerda-Brown C, Davey C, Whittle S, Allen N, Byrne M, Schwartz O . Mapping the relationship between subgenual cingulate cortex functional connectivity and depressive symptoms across adolescence. Soc Cogn Affect Neurosci. 2014; 10(7):961-8. PMC: 4483565. DOI: 10.1093/scan/nsu143. View

10.

Cullen K, Klimes-Dougan B, Muetzel R, Mueller B, Camchong J, Houri A . Altered white matter microstructure in adolescents with major depression: a preliminary study. J Am Acad Child Adolesc Psychiatry. 2010; 49(2):173-83.e1. PMC: 2909686. DOI: 10.1097/00004583-201002000-00011. View

11.

Pizzagalli D . Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology. 2010; 36(1):183-206. PMC: 3036952. DOI: 10.1038/npp.2010.166. View

12.

Somerville L, Jones R, Casey B . A time of change: behavioral and neural correlates of adolescent sensitivity to appetitive and aversive environmental cues. Brain Cogn. 2009; 72(1):124-33. PMC: 2814936. DOI: 10.1016/j.bandc.2009.07.003. View

13.

Andersen S . Trajectories of brain development: point of vulnerability or window of opportunity?. Neurosci Biobehav Rev. 2003; 27(1-2):3-18. DOI: 10.1016/s0149-7634(03)00005-8. View

14.

Ho T, Yang G, Wu J, Cassey P, Brown S, Hoang N . Functional connectivity of negative emotional processing in adolescent depression. J Affect Disord. 2013; 155:65-74. PMC: 4961511. DOI: 10.1016/j.jad.2013.10.025. View

15.

Drevets W, Savitz J, Trimble M . The subgenual anterior cingulate cortex in mood disorders. CNS Spectr. 2008; 13(8):663-81. PMC: 2729429. DOI: 10.1017/s1092852900013754. View

16.

Ernst M, Torrisi S, Balderston N, Grillon C, Hale E . fMRI functional connectivity applied to adolescent neurodevelopment. Annu Rev Clin Psychol. 2015; 11:361-77. PMC: 4990783. DOI: 10.1146/annurev-clinpsy-032814-112753. View

17.

Henderson S, Johnson A, Vallejo A, Katz L, Wong E, Gabbay V . A preliminary study of white matter in adolescent depression: relationships with illness severity, anhedonia, and irritability. Front Psychiatry. 2013; 4:152. PMC: 3839092. DOI: 10.3389/fpsyt.2013.00152. View

18.

Mulders P, van Eijndhoven P, Schene A, Beckmann C, Tendolkar I . Resting-state functional connectivity in major depressive disorder: A review. Neurosci Biobehav Rev. 2015; 56:330-44. DOI: 10.1016/j.neubiorev.2015.07.014. View

19.

Thompson R . Emotion regulation: a theme in search of definition. Monogr Soc Res Child Dev. 1994; 59(2-3):25-52. View

20.

Shenhav A, Botvinick M, Cohen J . The expected value of control: an integrative theory of anterior cingulate cortex function. Neuron. 2013; 79(2):217-40. PMC: 3767969. DOI: 10.1016/j.neuron.2013.07.007. View