Kate, age 14, is referred for follow-up treatment of depression after she impulsively swallowed a bottle of acetaminophen. She says she is in academic trouble and has no friends. Kate describes her childhood as mostly happy except for her parents’ arguments. Her medical history indicates she began developing breasts at age 10 and had her first menstrual period at age 12.
Her father is largely absent, traveling and working long hours. Her mother developed postpartum depression and stopped working after Kate’s younger brother was born.
Girls and boys show similar depression risks during childhood, but girls are twice as likely as boys to become clinically depressed after puberty. The key to treating depression in teen girls is to recognize that brain development and fluctuating hormones can influence behavior in ways that confuse them and the people around them. Successfully treating teen girls’ depression may require a gender-specific approach.
3 stages of brain development
Fetal differentiation. All brains start out with female-type brain circuits. At 8 weeks of fetal life, however, tiny testicles in the male begin to produce large amounts of testosterone, which changes the brain and body to male. Thus, sex-specific genes and hormones guide aspects of the first phase of brain development.1
Table 1
Female hormonal development: Gestation to puberty
| Stage/age | Hormonal events | Effect on female brain |
|---|---|---|
| Gestation | Components of reproductive axis form in early embryonic development; at 8 weeks, testosterone from fetal testicles begins to change female-type brain areas to male | Unperturbed by testosterone, brain continues to develop along female lines |
| Birth to age 24 months | Hormone-secreting placenta detaches at birth, dramatically increasing GnRH and LH/FSH and driving infant gonads to produce estrogen in girls or testosterone in boys (“infantile puberty”) | Abundant ovarian estrogen secretion enhances development of brain circuits, such as those associated with reproduction, maternal behavior, and social relatedness |
| Age 24 months to prepuberty | “Brakes” put on GnRH and LH/FSH pulsatile brain cells | “Juvenile pause” begins, with constant low estrogen secretion in girls by 24 months (in boys, “brakes” are on by 12 months) |
| Puberty | “Brakes” released on GnRH and LH/FSH neurons, reactivating reproductive axis | Ovary resumes estrogen production (“adolescent puberty”); increase in estrogen, progesterone, and testosterone stimulates brain circuit development; unipolar depression rates increase to 2:1 (female to male) by age 15 |
| GnRH: gonadotropin-releasing hormone; LH/FSH: luteinizing hormone/follicle-stimulating hormone | ||
| Source: References 4,5 | ||
Infantile puberty and the second phase of brain development begin in early childhood, as the ovaries and testicles start to produce large amounts of estrogen and testosterone soon after birth.
Puberty launches the final brain development phase. Up to 2 years before menstruation begins, pulsatile gonadotropin-releasing hormone cells in the hypothalamus wake up and start stimulating the ovaries to produce estrogen, thrusting the girl brain into puberty (Figure). The teen girl brain begins to experience not only estrogen surges from the ovary but progesterone and testosterone surges as well.
Although brain size and basic circuitry are mostly set by age 5, puberty stimulates new brain cells and increases myelin production.2 Faster myelinated connections between emotionally impulsive limbic brain areas such as the amygdala and sensible, cognitive areas such as the prefrontal cortex are not finished until the early 20s.3
Hormonal changes at puberty
The female brain is remodeled during puberty, leading to sexually dimorphic brain activation and development that further differentiates it from the male brain.4
Estrogen surges are associated with increased production of neurohormones and neurochemicals, such as:
- oxytocin, which reinforces social bonding and intimacy
- dopamine, which stimulates motivation and pleasure circuits in the brain.
Hormonal changes and brain development alter gene expression and affect neurodevelopment. These events may trigger a first depression in pubertal girls with a family history of mood disorder (Table 1).4,5 Although menarche has begun at an average age of 12 in the United States for decades, the most recent National Health and Examination Survey (NHANES) shows puberty onset in girls is occurring earlier (Table 2).6-9
Tanner stage—a measure of pubertal status—is a more accurate predictor of depression in teen girls than age.10 Pubertal transition to Tanner stage 3 (development of pubic and axillary hair and breast buds) is associated with a sharp increase in depression rates. Girls at stage 3 and higher are approximately 3 times more likely to be depressed than girls at stages 1 or 2.11
Pubic hair, breast development, and menstruation are markers for underlying hormonal changes (Table 3).4,5 The onset of estrogen, progesterone, and testosterone surges closely correlates with the difference in depression rates between pre- and postpubertal girls.12 After estrogen and progesterone surges begin at puberty, negative emotions exert an increased activating effect on the female brain,13 and social stressors more deeply affect girls than they do boys. This may explain why girls are more susceptible to depression when a friendship fails.14