Advertisement

Structural Connectivity Between Rostral Anterior Cingulate Cortex and Amygdala Predicts First Onset of Depressive Disorders in Adolescence

Published:February 18, 2021DOI:https://doi.org/10.1016/j.bpsc.2021.01.012

      Abstract

      Background

      Adolescent-onset depressive disorders (DDs) are associated with deficits in the regulation of negative affect across modalities (self-report, behavioral paradigms, and neuroimaging), which may manifest prior to first-onset DDs. Whether the neurocircuitry governing emotional regulation predates DDs is unclear. This study tested whether a critical pathway for emotion regulation (rostral anterior cingulate cortex–amygdala structural connectivity) predicts first-onset DDs in adolescent females.

      Methods

      Diffusion tensor imaging data were acquired on adolescent females (n = 212) without a history of DDs and the cohort was reassessed for first-onset DDs over the next 27 months.

      Results

      A total of 26 girls developed first onsets of DDs in the 27 months after imaging. Multivariate logistic regression showed that lower weighted average fractional anisotropy of uncinate fasciculus tracts between the rostral anterior cingulate cortex and amygdala prospectively predicted first onset of DDs (adjusted odds ratio = 0.44, p = .005), above and beyond established risk factors including baseline depression symptom severity, history of anxiety disorders, parental history of depression, parental education, and age.

      Conclusions

      This study provides evidence for the first time showing that aberrant structural connectivity between the rostral anterior cingulate cortex and amygdala prospectively predates first onset of DDs in adolescent females. These results highlight the importance of a well-established neural circuit implicated in the regulation of negative affect as a likely etiological factor and a promising target for intervention and prevention of DDs.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      References

        • World Health Organization
        Depression and Other Common Mental Disorders: Global Health Estimates.
        World Health Organization, Geneva, Switzerland2017
        • Salk R.H.
        • Hyde J.S.
        • Abramson L.Y.
        Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms.
        Psychol Bull. 2017; 143: 783-822
        • Muñoz R.F.
        • Beardslee W.R.
        • Leykin Y.
        Major depression can be prevented.
        Am Psychol. 2012; 67: 285
        • Singh I.
        • Rose N.
        Biomarkers in psychiatry.
        Nature. 2009; 460: 202-207
        • Gotlib I.H.
        • Joormann J.
        Cognition and depression: Current status and future directions.
        Annu Rev Clin Psychol. 2010; 6: 285-312
        • Johnstone T.
        • van Reekum C.M.
        • Urry H.L.
        • Kalin N.H.
        • Davidson R.J.
        Failure to regulate: Counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression.
        J Neurosci. 2007; 27: 8877-8884
        • Gross J.J.
        The emerging field of emotion regulation: An integrative review.
        Rev Gen Psychol. 1998; 2: 271-299
        • Rottenberg J.
        Emotions in depression: What do we really know?.
        Annu Rev Clin Psychol. 2017; 13: 241-263
        • Nolen-Hoeksema S.
        • Wisco B.E.
        • Lyubomirsky S.
        Rethinking rumination.
        Perspect Psychol Sci. 2008; 3: 400-424
        • Aldao A.
        • Nolen-Hoeksema S.
        • Schweizer S.
        Emotion-regulation strategies across psychopathology: A meta-analytic review.
        Clin Psychol Rev. 2010; 30: 217-237
        • Joormann J.
        • Gotlib I.H.
        Emotion regulation in depression: Relation to cognitive inhibition.
        Cogn Emot. 2010; 24: 281-298
        • Nook E.C.
        • Sasse S.F.
        • Lambert H.K.
        • McLaughlin K.A.
        • Somerville L.H.
        The nonlinear development of emotion differentiation: Granular emotional experience is low in adolescence.
        Psychol Sci. 2018; 29: 1346-1357
        • Larson R.
        • Csikszentmihalyi M.
        • Graef R.
        Mood variability and the psychosocial adjustment of adolescents.
        J Youth Adolesc. 1980; 9: 469-490
        • Larson R.
        • Lampman-Petraitis C.
        Daily emotional states as reported by children and adolescents.
        Child Dev. 1989; : 1250-1260
        • Zimmermann P.
        • Iwanski A.
        Emotion regulation from early adolescence to emerging adulthood and middle adulthood: Age differences, gender differences, and emotion-specific developmental variations.
        Int J Behav Dev. 2014; 38: 182-194
        • Silk J.S.
        • Steinberg L.
        • Morris A.S.
        Adolescents' emotion regulation in daily life: Links to depressive symptoms and problem behavior.
        Child Dev. 2003; 74: 1869-1880
        • Shackman A.J.
        • Salomons T.V.
        • Slagter H.A.
        • Fox A.S.
        • Winter J.J.
        • Davidson R.J.
        The integration of negative affect, pain and cognitive control in the cingulate cortex.
        Nat Rev Neurosci. 2011; 12: 154-167
        • Mohanty A.
        • Engels A.S.
        • Herrington J.D.
        • Heller W.
        • Ho M.H.
        • Banich M.T.
        • et al.
        Differential engagement of anterior cingulate cortex subdivisions for cognitive and emotional function.
        Psychophysiology. 2007; 44: 343-351
        • Etkin A.
        • Egner T.
        • Kalisch R.
        Emotional processing in anterior cingulate and medial prefrontal cortex.
        Trends Cogn Sci. 2011; 15: 85-93
        • Bissiere S.
        • Plachta N.
        • Hoyer D.
        • McAllister K.H.
        • Olpe H.R.
        • Grace A.A.
        • et al.
        The rostral anterior cingulate cortex modulates the efficiency of amygdala-dependent fear learning.
        Biol Psychiatry. 2008; 63: 821-831
        • Palomero-Gallagher N.
        • Mohlberg H.
        • Zilles K.
        • Vogt B.
        Cytology and receptor architecture of human anterior cingulate cortex.
        J Comp Neurol. 2008; 508: 906-926
        • Devinsky O.
        • Morrell M.J.
        • Vogt B.A.
        Contributions of anterior cingulate cortex to behaviour.
        Brain. 1995; 118: 279-306
        • Coad B.M.
        • Postans M.
        • Hodgetts C.J.
        • Muhlert N.
        • Graham K.S.
        • Lawrence A.D.
        Structural connections support emotional connections: Uncinate fasciculus microstructure is related to the ability to decode facial emotion expressions.
        Neuropsychologia. 2017; 145: 106562
        • LeWinn K.Z.
        • Connolly C.G.
        • Wu J.
        • Drahos M.
        • Hoeft F.
        • Ho T.C.
        • et al.
        White matter correlates of adolescent depression: Structural evidence for frontolimbic disconnectivity.
        J Am Acad Child Adolesc Psychiatry. 2014; 53 (e1-7): 899-909
        • de Kwaasteniet B.
        • Ruhe E.
        • Caan M.
        • Rive M.
        • Olabarriaga S.
        • Groefsema M.
        • et al.
        Relation between structural and functional connectivity in major depressive disorder.
        Biol Psychiatry. 2013; 74: 40-47
        • Cullen K.R.
        • Klimes-Dougan B.
        • Muetzel R.
        • Mueller B.A.
        • Camchong J.
        • Houri A.
        • et al.
        Altered white matter microstructure in adolescents with major depression: A preliminary study.
        J Am Acad Child Adolesc Psychiatry. 2010; 49: 173-183.e1
        • Kaufman J.
        • Birmaher B.
        • Brent D.
        • Rao U.
        • Flynn C.
        • Moreci P.
        • et al.
        Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Initial reliability and validity data.
        J Am Acad Child Adolesc Psychiatry. 1997; 36: 980-988
        • Jin J.
        • Narayanan A.
        • Perlman G.
        • Luking K.
        • DeLorenzo C.
        • Hajcak G.
        • et al.
        Orbitofrontal cortex activity and connectivity predict future depression symptoms in adolescence.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2017; 2: 610-618
        • Jin J.
        • Van Snellenberg J.X.
        • Perlman G.
        • DeLorenzo C.
        • Klein D.N.
        • Kotov R.
        • et al.
        Intrinsic neural circuitry of depression in adolescent females.
        J Child Psychol Psychiatry. 2020; 61: 480-491
        • Nelson B.D.
        • Perlman G.
        • Klein D.N.
        • Kotov R.
        • Hajcak G.
        Blunted neural response to rewards as a prospective predictor of the development of depression in adolescent girls.
        Am J Psychiatry. 2016; 173: 1223-1230
        • First M.
        • Gibbon M.
        • Spitzer R.
        • Williams J.
        User’s Guide for the Structured Interview for DSM-IV Axis I Disorders–Research Version (SCID-I, Version 2.0, February 1996 Final Version).
        Biometrics Research, New York1996
        • Watson D.
        • O’Hara M.W.
        • Naragon-Gainey K.
        • Koffel E.
        • Chmielewski M.
        • Kotov R.
        • et al.
        Development and validation of new anxiety and bipolar symptom scales for an expanded version of the IDAS (the IDAS-II).
        Assessment. 2012; 19: 399-420
        • Liu Z.
        • Wang Y.
        • Gerig G.
        • Gouttard S.
        • Tao R.
        • Fletcher T.
        • et al.
        Quality control of diffusion weighted images.
        Proc SPIE Int Soc Opt Eng. 2010; 7628: 76280J
        • Jones D.K.
        • Basser P.J.
        "Squashing peanuts and smashing pumpkins": How noise distorts diffusion-weighted MR data.
        Magn Reson Med. 2004; 52: 979-993
        • Alexander D.C.
        • Barker G.J.
        Optimal imaging parameters for fiber-orientation estimation in diffusion MRI.
        Neuroimage. 2005; 27: 357-367
        • Iscan Z.
        • Jin T.B.
        • Kendrick A.
        • Szeglin B.
        • Lu H.
        • Trivedi M.
        • et al.
        Test-retest reliability of freesurfer measurements within and between sites: Effects of visual approval process.
        Hum Brain Mapp. 2015; 36: 3472-3485
        • Fischl B.
        • Salat D.H.
        • Busa E.
        • Albert M.
        • Dieterich M.
        • Haselgrove C.
        • et al.
        Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain.
        Neuron. 2002; 33: 341-355
        • Behrens T.E.
        • Berg H.J.
        • Jbabdi S.
        • Rushworth M.F.
        • Woolrich M.W.
        Probabilistic diffusion tractography with multiple fibre orientations: What can we gain?.
        Neuroimage. 2007; 34: 144-155
        • Thapar A.
        • Collishaw S.
        • Pine D.S.
        • Thapar A.K.
        Depression in adolescence.
        Lancet. 2012; 379: 1056-1067
        • Stein M.B.
        • Fuetsch M.
        • Müller N.
        • Höfler M.
        • Lieb R.
        • Wittchen H.-U.
        Social anxiety disorder and the risk of depression: A prospective community study of adolescents and young adults.
        Arch Gen Psychiatry. 2001; 58: 251-256
        • Soares J.M.
        • Marques P.
        • Alves V.
        • Sousa N.
        A hitchhiker's guide to diffusion tensor imaging.
        Front Neurosci. 2013; 7: 31
        • Vogt B.A.
        Pain and emotion interactions in subregions of the cingulate gyrus.
        Nat Rev Neurosci. 2005; 6: 533-544
        • Sotres-Bayon F.
        • Quirk G.J.
        Prefrontal control of fear: More than just extinction.
        Curr Opin Neurobiol. 2010; 20: 231-235
        • Quirk G.J.
        • Likhtik E.
        • Pelletier J.G.
        • Pare D.
        Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons.
        J Neurosci. 2003; 23: 8800-8807
        • Janak P.H.
        • Tye K.M.
        From circuits to behaviour in the amygdala.
        Nature. 2015; 517: 284-292
        • Gee D.G.
        • Humphreys K.L.
        • Flannery J.
        • Goff B.
        • Telzer E.H.
        • Shapiro M.
        • et al.
        A developmental shift from positive to negative connectivity in human amygdala-prefrontal circuitry.
        J Neurosci. 2013; 33: 4584-4593
        • Shen X.
        • Finn E.S.
        • Scheinost D.
        • Rosenberg M.D.
        • Chun M.M.
        • Papademetris X.
        • et al.
        Using connectome-based predictive modeling to predict individual behavior from brain connectivity.
        Nat Protoc. 2017; 12: 506-518
        • Finn E.S.
        • Shen X.
        • Scheinost D.
        • Rosenberg M.D.
        • Huang J.
        • Chun M.M.
        • et al.
        Functional connectome fingerprinting: Identifying individuals using patterns of brain connectivity.
        Nat Neurosci. 2015; 18: 1664-1671
        • Hsu W.T.
        • Rosenberg M.D.
        • Scheinost D.
        • Constable R.T.
        • Chun M.M.
        Resting-state functional connectivity predicts neuroticism and extraversion in novel individuals.
        Soc Cogn Affect Neurosci. 2018; 13: 224-232
        • Feng C.
        • Yuan J.
        • Geng H.
        • Gu R.
        • Zhou H.
        • Wu X.
        • et al.
        Individualized prediction of trait narcissism from whole-brain resting-state functional connectivity.
        Hum Brain Mapp. 2018; 39: 3701-3712
        • Beaty R.E.
        • Kenett Y.N.
        • Christensen A.P.
        • Rosenberg M.D.
        • Benedek M.
        • Chen Q.
        • et al.
        Robust prediction of individual creative ability from brain functional connectivity.
        Proc Natl Acad Sci U S A. 2018; 115: 1087-1092
        • Rosenberg M.D.
        • Finn E.S.
        • Scheinost D.
        • Papademetris X.
        • Shen X.
        • Constable R.T.
        • et al.
        A neuromarker of sustained attention from whole-brain functional connectivity.
        Nat Neurosci. 2016; 19: 165-171
        • Kendler K.S.
        • Gardner C.O.
        • Prescott C.A.
        Toward a comprehensive developmental model for major depression in men.
        Am J Psychiatry. 2006; 163: 115-124
        • Kendler K.S.
        • Gardner C.O.
        • Prescott C.A.
        Toward a comprehensive developmental model for major depression in women.
        Am J Psychiatry. 2002; 159: 1133-1145
        • Casey B.J.
        Beyond simple models of self-control to circuit-based accounts of adolescent behavior.
        Annu Rev Psychol. 2015; 66: 295-319
        • Swartz J.R.
        • Carrasco M.
        • Wiggins J.L.
        • Thomason M.E.
        • Monk C.S.
        Age-related changes in the structure and function of prefrontal cortex-amygdala circuitry in children and adolescents: A multi-modal imaging approach.
        Neuroimage. 2014; 86: 212-220
        • Joormann J.
        • Stanton C.H.
        Examining emotion regulation in depression: A review and future directions.
        Behav Res Ther. 2016; 86: 35-49