Evidence-Based Reviews

Teen girl brain: High drama, high risk for depression

Current Psychiatry. 2007 May;6(5):63-70

References

1. Arnold AP. Sex chromosomes and brain gender. Nat Rev Neurosci 2004;5(9):701-8.

2. Giedd JN, Snell JW, Lange N, et al. Quantitative magnetic resonance imaging of human brain development: ages 4-18. Cereb Cortex 1996;6(4):551-60.

3. Yurgelun-Todd DA. Emotional and cognitive changes during adolescence. Curr Opin Neurobiol. In press.

4. Cameron J. Interrelationships between hormones, behavior, and affect during adolescence: understanding hormonal, physical, and brain changes occurring in association with pubertal activation of the reproductive axis. Ann NY Acad Sci 2004;1021:110-23.

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6. Biro F, Huang B, Crawford P, et al. Pubertal correlates in black and white girls. J Pediatr 2006;148(2):234-40.

7. Herman-Giddens M, Kaplowitz P, Wasserman R. Navigating the recent articles on girls’ puberty in pediatrics: what do we know and where do we go from here? Pediatrics 2004;113(4):911-7.

8. Herman-Giddens M, Slora E, Wasserman R, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 1997;99(4):505-12.

9. Wu T, Mendola P, Buck G. Ethnic differences in the presence of secondary sex characteristics and menarche among US girls: the Third National Health and Nutrition Examination Survey, 1988-1994. Pediatrics 2002;110(4):752-7.

10. Rapkin A, Tsao J, Turk N, et al. Relationships among self-rated Tanner staging, hormones, and psychosocial factors in healthy female adolescents. J Pediatr Adolesc Gynecol 2006;19:181-7.

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13. Hofer A, Siedentopf CM, Ischebeck A, et al. Gender differences in regional cerebral activity during the perception of emotion: a functional MRI study. Neuroimage 2006;32(2):854-62.

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16. Williams LM, Barton MJ, Kemp AH, et al. Distinct amygdala-autonomic arousal profiles in response to fear signals in healthy males and females. Neuroimage 2005;28(3):618-26.

17. Killgore WD, Yurgelun-Todd DA. Sex-related developmental differences in the lateralized activation of the prefrontal cortex and amygdala during perception of facial affect. Percept Mot Skills 2004;99(2):371-91.

18. Cheng YW, Tzeng OJ, Decety J, et al. Gender differences in the human mirror system: a magnetoencephalography study. Neuroreport 2006;17(11):1115-9.

19. Schmidt PJ, Nieman LK, Danaceau MA, et al. Differential behavioral effects of gonadal steroids in women with and those without premenstrual syndrome. N Engl J Med 1998;338(4):209-16.

20. Staley J, Sanacora G, Tamagnan G, et al. Sex differences in diencephalon serotonin transporter availability in major depression. Biol Psychiatry 2006;59:40-7.

21. Caspi A, Sugden K, Moffitt T, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003;301:386-9.

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Genetic factors. Kate’s mother’s history of postpartum depression suggests genetic risk for Kate. Studies have found that the expression of particular genes—such as the serotonin transporter (5-HTT) gene—may be associated with depression. Staley et al²⁰ found that depressed women show a significantly greater decrease in 5-HTT availability in the diencephalon (forebrain region containing the thalamus, hypothalamus, and part of the pituitary gland) when compared with healthy women and depressed men.

Table 3

3 stages of girls’ gonadal development

Stage	Timing	Developmental events
Adrenarche	Onset around age 6, peaks by age 20	Rise in weak androgens (DHEA and DHEAS) from adrenal gland results in pubic and axillary hair and increases likelihood of acne
Gonadarche	Usually ~2 years before menarche	Pulses of GnRH, LH/FSH lead to increased estrogen, which stimulates breast development, widening of hips, and increased subcutaneous fat deposition
Menarche	Relatively late in puberty (usually not before Tanner stage 4)	“Monthly” cycle established; ovarian estrogen pulses in response to GnRH and FSH, the LH surge, and ovulation; progesterone produced after ovulation
DHEA: dehydroepiandrosterone; DHEAS: dehydroepiandrosterone sulfate; GnRH: gonadotropin-releasing hormone;
LH/FSH: luteinizing hormone/follicle-stimulating hormone
Tanner stage 4: pubic hair and breast development typical of middle to late adolescence (ages 12 to 17)
Source: References 4,5

Although men and women have the same 5-HTT gene, women may possess a gender-specific factor—such as estrogen or progesterone—that differentially alters this and other genes’ expression in women with depression. Individuals who carry a short version of the gene may be at particular risk of becoming depressed when exposed to stressful life events.

Clinical Point

Use weekly psychotherapy to provide depressed teen girls with tools to manage stress and impulsive behavior

Caspi et al²¹ found a polymorphism in the 5-HTT gene on chromosome 17 that can manifest differentially based on environmental factors. In this study, individuals with 2 copies of the long version of this gene were relatively resistant to stressful life events, whereas those with 1 or 2 copies of the short version were highly sensitive to stressful life events. The depression rate in short-gene individuals was:

9% in those who had not experienced stressful life events
nearly 40% in those who had experienced ≥4 stressful life events.

Hormonal and stress factors. Stress responsiveness becomes sexually dimorphic at puberty. Compared with men, women are:

at greater risk after puberty for heightened stress responsiveness, which is associated with major depressive disorder
3 times more likely to develop depression after a stressful life event.²²

Women’s and men’s different biological responses to stress might be related to the gender-specific hormones that emerge during puberty. Kate could be at increased risk for depression—especially immediately before her period—if she inherited a stress-sensitive gene and now has increased stress sensitivity triggered by the hormones of puberty.²³

Neurodevelopmental factors. Dorsolateral prefrontal cortex circuits associated with making good decisions and weighing the consequences of actions are immature in the adolescent and the last part of the brain to undergo myelination.^24-26 Teens are well-known for erratic, emotionally driven behaviors.^27,28 Kate’s impulsive overdose exemplifies the consequences of emotional reactivity without the benefit of inhibitory mature brain connections.

Related resources

Brizendine L. Teen girl brain. In: The female brain. New York: Morgan Road Books; 2006:31-56. www.thefemalebrain.com.
Strauch B. The primal teen: what discoveries about the teenage brain tell us about our kids. New York: Doubleday; 2003.
Harter S. Self and identity development. In: Feldman S, Elliott G, eds. At the threshold: the developing adolescent. Cambridge, MA: Harvard University Press; 1990:352-87.

Drug brand names

Ethinyl estradiol/levonorgestrel • Seasonale

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.