Stress, sensitive periods and maturational events in adolescent depression

doi:10.1016/j.tins.2008.01.004

Trends in Neurosciences

Volume 31, Issue 4, April 2008, Pages 183-191

https://doi.org/10.1016/j.tins.2008.01.004 Get rights and content

In this paper, we provide an overview of how the maturation of specific brain regions and stress exposure during windows of vulnerability initiate a series of events that render adolescents exceptionally susceptible to the development of depression. This stress-incubation/corticolimbic development cascade provides a means of understanding why depression emerges with such force and frequency in adolescence. The development of the prefrontal cortex, hippocampus, amygdala and ventral striatum is described from a translational perspective as they relate to stress exposure, onset, pathogenesis and gender differences in depression. Adolescent depression is a serious recurrent brain-based disorder. Understanding the genesis and neurobiological basis is important in the development of more effective intervention strategies to treat or prevent the disorder.

Introduction

The overriding issue of this review is to understand why depression emerges with such force and frequency in adolescence, particularly in young women. Conceivably, a host of psychosocial factors can render adolescents especially vulnerable, but our focus will be on neurobiological factors. In particular, we will examine the interplay of genetic, maturational and experiential factors affecting mood using a translational perspective that melds clinical and basic laboratory findings.

Section snippets

Basic epidemiology of adolescent depression

Major depression disorder is a common and serious disorder of adolescence [1]. Lifetime prevalence increases dramatically from 1% of the population under age 12 to ∼17%–25% of the population by the end of adolescence [2]. The greatest surge in newly emergent cases occurs between 15 and 18 years [3].

Cross-sectional and prospective epidemiological studies indicate that anxiety disorders often precede the emergence of depression and identify children at risk for developing depression 4, 5. It is

Etiology of depression

Although the specific etiology of major depression remains unknown, both heredity and early experience are critical determinants. Further, maturational events might potentially increase prevalence or trigger episodes (see Box 1). It is important to distinguish between specific etiological factors (e.g. genetic polymorphisms, childhood adversity) that increase risk in selective recipients and universal phenomena (e.g. puberty) that exert moderating effects on the entire population.

Effects of early stress on brain development—evidence for sensitive periods

Early stress stemming from childhood adversity is a predisposing risk factor for the development of major depression [15], and depression is the most common adult sequela of early abuse [35]. Whether exposure to adversity leads to the eventual development of depression is likely to be determined by genetic susceptibilities [16], frequency, severity and multiplicity of the stressors 16, 36, gender and timing of insult [37]. Exposure to physical or sexual abuse resulting in psychopathology has

Maturation and onset of depression

Depression is the most extensively documented outcome of exposure to CSA in adults but is not a common occurrence in children [35]. This suggests that a substantial time lag, or incubation period, occurs between early stress exposure and eventual development of depression. In a prospective study, rates of depression were increased by physical abuse or neglect (n = 676), which lead to an earlier emergence of depression relative to controls (n = 520) [48]. In a separate cohort exposed to CSA but no

Delayed effects of early stress on the hippocampus

The role of the hippocampus in adolescent depression is highly likely, given its susceptibility to the effects of stress [50] and its role in mood regulation and antidepressant response [51]. Reduced hippocampal size has been observed in most studies of adults with major depression [39], and can vary as a function of episode number [39] or duration of time spent depressed but untreated [32]. We propose that the hippocampus contributes to the burden of depression by failing to provide an

Late-maturing prefrontal cortex

Multiple components of the prefrontal cortex (PFC) are involved in the emergence of depression as it matures during the periadolescent period. A primary role of the PFC is to modulate activity of limbic structures. The PFC has a protracted postnatal ontogeny and does not attain adult volume until the early 20s [58]. The complexity of the region and its developmental time course render it vulnerable, especially to stress during adolescence [46]. PFC development is also affected by early

The amygdala: fear, irritability and anxiety

The amygdala has become an increasingly important component of theories of depression, based largely on imaging studies of mood regulation. The amygdala is over-responsive to fearful stimuli in depression [66], and insufficiently regulated by PFC controls [67]. This leads to an excessive and persistent degree of negative affectivity, which is a significant but nonspecific feature of depression. Alteration in the genes encoding 5-HTT and 5HT1 is associated with augmented amygdala response to

Conclusions

Recent studies have emphasized the importance of gene x environment in the genesis of depression. Time is another crucial factor, both in terms of windows of vulnerability when brain regions might be maximally sensitive to environmental influences and in the cascade of maturational events that lead to the unfolding of depression. The hippocampus and PFC can have early and late windows of vulnerability, and serve respectively as targets for the predisposing and precipitating effects of stress.

Acknowledgements

This work was supported, in part, by awards from NARSAD (2001, 2002, 2005), NIDA (RO1DA-017846), NIMH (RO1MH-66222) and the Simches and Rosenberg Families.

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Trends in Neurosciences

ReviewStress, sensitive periods and maturational events in adolescent depression

Introduction

Section snippets

Basic epidemiology of adolescent depression

Etiology of depression

Effects of early stress on brain development—evidence for sensitive periods

Maturation and onset of depression

Delayed effects of early stress on the hippocampus

Late-maturing prefrontal cortex

The amygdala: fear, irritability and anxiety

Conclusions

Acknowledgements

Biol. Psychiatry

Child Adolesc. Psychiatr. Clin. N. Am.

J. Psychiatr. Res.

J. Affect. Disord.

J. Am. Acad. Child Adolesc. Psychiatry

J. Am. Acad. Child Adolesc. Psychiatry

J. Affect. Disord.

J. Affect. Disord.

Neurosci. Biobehav. Rev.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Psychoneuroendocrinology

Neuroimage

Mol. Cell. Endocrinol.

Neuroscience

Child Adolesc. Psychiatr. Clin. N. Am.

Brain Res. Rev.

J. Am. Acad. Child Adolesc. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Neurosci. Biobehav. Rev.

Curr. Top. Dev. Biol.

Biol. Psychiatry

Neuron

J. Am. Acad. Child Adolesc. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Neurosci. Biobehav. Rev.

Neurosci. Lett.

Brain Res. Dev. Brain Res.

Neurobiol. Aging

Biol. Psychiatry

Neurosci. Biobehav. Rev.

Trends Pharmacol. Sci.

Continuation and maintenance therapy of early-onset major depressive disorder

Paediatr. Drugs

Development of depression from preadolescence to young adulthood: emerging gender differences in a 10-year longitudinal study

J. Abnorm. Psychol.

Incidence of social anxiety disorder and the consistent risk for secondary depression in the first three decades of life

Arch. Gen. Psychiatry

Preadult onset vs. adult onset of major depressive disorder: a replication study

Acta Psychiatr. Scand.

Menarche and the onset of depression and anxiety in Victoria, Australia

J. Epidemiol. Community Health

Review
Stress, sensitive periods and maturational events in adolescent depression