New research
Brain Structural Signatures of Adolescent Depressive Symptom Trajectories: A Longitudinal Magnetic Resonance Imaging Study

https://doi.org/10.1016/j.jaac.2017.05.008Get rights and content

Objective

Most evidence for structural brain abnormalities associated with adolescent depression is based on cross-sectional study designs that do not take into account the dynamic course of depressive symptoms and brain maturation across adolescence. In this study, a longitudinal design was used to investigate the association between different trajectories of depressive symptoms and longitudinal changes in brain structure throughout adolescence.

Method

One hundred forty-nine adolescents were assessed on depressive symptoms and underwent structural magnetic resonance imaging at 12 years of age and were followed up multiple times until 19 years. Three depressive symptom trajectories (low-stable [n = 97], early-decreasing [n = 33], late-increasing [n = 19]) were identified, and effects of group and group by time on hippocampus and amygdala volume and prefrontal cortical thickness and surface area were evaluated.

Results

The early-decreasing symptoms group exhibited differences in cortical surface area compared to the low-stable and late-increasing symptoms groups, moderated by sex. Specifically, females in the early-decreasing symptoms group showed lower anterior cingulate and orbitofrontal cortex surface areas across adolescence compared to females in the other groups. Males in the early-decreasing symptoms group showed lower right orbitofrontal cortex surface area expansion over time compared to males in the low-stable and late-increasing symptoms groups. No effects were found for cortical thickness or for hippocampus and amygdala volume.

Conclusion

Alterations in cortical surface area were specifically observed in young people experiencing depressive symptoms in early adolescence. These findings suggest that early adolescence is a particularly sensitive period for cortical surface area abnormalities associated with depressive symptoms and could provide a critical window for treatment of (subthreshold) depressive symptoms.

Section snippets

Participants

Participants were those from the Orygen Adolescent Development Study (ADS). The ADS is a longitudinal study aimed at providing insight into risk and resilience factors for depression during adolescence (for a detailed description of the ADS study and selection criteria, see Whittle et al.20). Neuroimaging data were collected at wave 1, wave 3, and wave 4. For the present study, we included a subgroup of 149 participants from whom structural magnetic resonance imaging (MRI) data were available

Results

Demographic and clinical characteristics are presented in Table 1. The different trajectory groups did not differ in sex (χ2[2, n = 149] = 1.91, p = .39), age at each wave (wave 1 F2,121 = 1.56, p = .21; wave 3 F2,129 = 1.40, p = .25; wave 4 F2,94 = 0.67, p = .51), SES (F2,141 = 1.19, p = .31), IQ (F2,131 = 1.14, p = .87), parental history of depression (χ2[2, n = 117] = 3.68, p = .16), and pubertal stage (F2,117 = 2.72, p = .07). Information on CES-D scores and global functioning for each

Discussion

This study investigated whether different longitudinal trajectories of depressive symptoms were associated with developmental changes in the gray matter of cortical and subcortical brain regions during adolescence. We found evidence for alterations in structural development in the group of adolescents who showed depressive symptoms early in adolescence that decreased over time (early-decreasing symptoms group), specifically for surface area of the ACC and OFC. These effects were moderated by

References (61)

  • T.L. Jernigan et al.

    Toward an integrative science of the developing human mind and brain: focus on the developing cortex

    Dev Cogn Neurosci

    (2016)
  • A. Angold et al.

    Puberty and depression

    Child Adolesc Psychiatr Clin N Am

    (2006)
  • E.T. Rolls et al.

    The orbitofrontal cortex and beyond: from affect to decision-making

    Prog Neurobiol

    (2008)
  • C. Diener et al.

    A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression

    Neuroimage

    (2012)
  • A.M. Winkler et al.

    Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies

    Neuroimage

    (2010)
  • P. Rakic

    A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution

    Trends Neurosci

    (1995)
  • P. Habets et al.

    Genetic Risk and Outcome of Psychosis (G.R.O.U.P). Reduced cortical thickness as an outcome of differential sensitivity to environmental risks in schizophrenia

    Biol Psychiatry

    (2011)
  • I. Yaroslavsky et al.

    Heterogeneous trajectories of depressive symptoms: adolescent predictors and adult outcomes

    J Affect Disord

    (2013)
  • H. Vulser et al.

    Subthreshold depression and regional brain volumes in young community adolescents

    J Am Acad Child Adolesc Psychiatry

    (2015)
  • C. Alexandrino-Silva et al.

    Gender differences in symptomatic profiles of depression: results from the São Paulo Megacity Mental Health Survey

    J Affect Disord

    (2013)
  • P.B. Repetto et al.

    Trajectories of depressive symptoms among high risk African-American adolescents

    J Adolesc Heal

    (2004)
  • R.C. Kessler et al.

    Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication

    Arch Gen Psychiatry

    (2005)
  • J.L. Luby et al.

    Early childhood depression and alterations in the trajectory of gray matter maturation in middle childhood and early adolescence

    JAMA Psychiatry

    (2016)
  • E. Fombonne et al.

    The Maudsley long-term follow-up of child and adolescent depression. Part 2: Suicidality, criminality and social dysfunction in adulthood

    Br J Psychiatry

    (2001)
  • E. Fombonne et al.

    The Maudsley long-term follow-up of child and adolescent depression. Part 1: Psychiatric outcomes in adulthood

    Br J Psychiatry

    (2001)
  • V. Dunn et al.

    Longitudinal investigation into childhood-and adolescence-onset depression: psychiatric outcome in early adulthood

    Br J Psychiatry

    (2006)
  • S. Whittle et al.

    Structural brain development and depression onset during adolescence: a prospective longitudinal study

    Am J Psychiatry

    (2014)
  • K.A.S. Wickrama et al.

    Family antecedents and consequences of trajectories of depressive symptoms from adolescence to young adulthood: a life course investigation

    J Health Soc Behav

    (2008)
  • M. Brendgen et al.

    Relations with parents and with peers, temperament, and trajectories of depressed mood during early adolescence

    J Abnorm Child Psychol

    (2005)
  • D. Costello et al.

    Risk and protective factors associated with trajectories of depressed mood from adolescence to early adulthood

    J Clin Psychol

    (2008)
  • Cited by (29)

    • Age related sex differences in maladaptive regulatory responses to sadness: A study of youths at high and low familial risk for depression

      2021, Journal of Affective Disorders
      Citation Excerpt :

      What mechanisms could account for our results? A major contributor may be the well documented sex differences in brain development, which are believed to play a mechanistic role in the emergence of sex disparities in rates of affective disorders (Andre et al., 2020; Schmaal et al., 2017; Whittle et al., 2014). More specifically, there is some (albeit limited) evidence that some features of brain development unfold faster (hence at an earlier age) in girls than in boys (see Lenroot and Giedd, 2010 for a review; also see Giedd et al., 1999).

    • Subclinical Anxiety and Posttraumatic Stress Influence Cortical Thinning During Adolescence

      2021, Journal of the American Academy of Child and Adolescent Psychiatry
    View all citing articles on Scopus

    This research was supported by grants from the Colonial Foundation, the National Health and Medical Research Council (NHMRC; Program Grant 350241) of Australia, and the Australian Research Council (Discovery Grant DP0878136). Dr. Schmaal gratefully acknowledges support from the foundation De Drie Lichten in The Netherlands, The Netherlands Brain Foundation (F2014[1]-24), and the Neuroscience Campus Amsterdam (IPB-SE-15-PSYCH-Schmaal). Dr. Yücel was supported by the NHMRC of Australia (ID APP1021973), and Dr. Whittle is supported by an NHMRC Career Development Fellowship (ID 1007716).

    Disclosure: Drs. Schmaal, Yücel, Ellis, Vijayakumar, Simmons, Allen, and Whittle report no biomedical financial interests or potential conflicts of interest.

    View full text