Studies that do track sex have reported intriguing findings related to brain development
and function. Speaker Dr. Elizabeth Sowell, at the University of California, Los Angeles, noted that there are gender differences
in the trajectory of gray matter maturation in adolescent girls and boys that may have lasting effects on the brain. Dr. Cheryl Sisk of Michigan State University reported on work in rats showing that pubertal hormones influence
the addition of new cells to areas of the brain that show sex-related differences, thus demonstrating the role of these hormones in maintaining these structural differences.
Several speakers talked about sex hormone effects on learning and memory. Dr. Larry Cahill, University of California, Irvine, noted that, in women, stress hormones affect memory differently, depending on the phase of the menstrual
cycle. Men and women viewing emotionally
charged films show activation of different sides of the amygdala, a part of the brain that is central to emotional memory: in men, the right amygdala is activated, in women, the left amygdala
is activated. Even the activity of the amygdala
at rest is different in men and women. Dr. Tracey Shors of Rutgers University reported that, in work with rats, stress improves learning in males, but impairs it in females.
Even prenatally, stress has different effects on male and female offspring. Dr. Tracy Bale, at the University of Pennsylvania, reported on research in mice showing that maternal stress early in pregnancy affected how male offspring responded to stressful situations; they responded
more like females. This work suggests differences
in effects of early vs. late prenatal stress and may offer clues to why prenatal stress is associated with greater risk of such disorders as depression, anxiety, schizophrenia and autism.
One of the goals of this research is to identify
how sex differences are established and maintained in the brain. Genes on the X and Y chromosomes set in motion the processes of sexual differentiation. The expression of numerous
genes on non-sex, or autosomal, chromosomes,
also differs according to whether they are inherited from the mother or father, a process
called imprinting. Understanding imprinting
could lead to therapies for disorders that are shaped by paternal or maternal inheritance of an abnormal gene.
During development, sex hormones have so-called organizational effects on the brain that persist once established, even if the hormones are removed, and activational effects, which depend on the continued presence of hormones.
Finally, experience can shape gene expression and with it, sexual differentiation and behavior. Speaker Dr. Anthony Auger of the University of Wisconsin reported that in rats, mothers groom male and female offspring differently; the differential
can alter gene expression and can contribute
to sex differences in the brain, with lasting
effects on social and emotional behavior. Social deficits are a feature of some neurodevelopmental
disorders; knowledge of these mechanisms
could provide clues to therapy.
NIMH intramural investigator Dr. Jay Giedd, who has been using MRI to conduct a long-term study of brain development, emphasized that there is enormous variability among individuals.
Differences between groups do not imply individual differences.Trajectories, rather than one-time measurements, determine IQ, health and illness and male/female differences.
Developmental trajectories also predict periods of vulnerability to illness and effective intervention.
Dr. Arthur Arnold of UCLA speculated that identifying the factors that protect one or the other sex from disease could lead to novel therapies that enhance those factors.
In any event, the full range of sex differences in neural connectivity—and their implications for understanding and treating mental illness—remain to be fully explored.