I.

The Biology
   When we see a man or a woman we can usually tell the difference between the genders
pretty easily. But sexual differentiation is not as simple as it seems at first glance.  There
are multiple levels of sexual differentiation. The most basic and molecular is genetic, i.e.,
at the level of the sex chromosomes; the X and the Y. Humans have 23 pairs of
chromosomes for a total of 46. The 23rd pair is the sex chromosomes. The Y
chromosome is the chromosome that determines "maleness." Men have a combination of
the X the Y. Women have two X chromosomes.  Therefore, women can only contribute an
ovum with an X chromosome. Men can contribute a sperm with either an X or a Y
chromosome.  So, it is the male's sperm that will determine if the offspring will be male
(XY) or female (XX).  Then there is differentiation at the level of the gonadal tissue. 
The same tissue in the developing embryo becomes either male gonads (testes) or female
gonads (ovaries).  There are no true hermaphrodites in humans, despite what people may
tell you on the "street corner."  True hermaphroditism describes having both male and
female functional gonadal systems which is typically seen only in invertebrates such as
earthworms and slugs.  At the level of the internal sex organs, each embryo has both
male and female internal sexual organs but during development one system develops and
the other system deteriorates and disappears.  The male system is the Wolffian system
which consists of epididymis, vas deferens, and seminal vesicles.  The female system is
the Mullerian system which consists of the uterus, fallopian tubes, and inner one third of
the vaginal canal.  At the level of the external sex organs, the same tissue will become
either male or female genitalia (penis and scrotum or clitoris and labia). Secondary sex
traits like body hair, breast development, muscle mass, fat deposition, proceed later in
life during puberty. However, during embryological and fetal development the brain is
also differentiated by sex hormones, which is manifested at the gross structural level by
differences in the size of the corpus callosum as well as the size of some hypothalamic
nuclei.
 
Sex Hormones
   The sex hormones are steroid hormones and are structurally related to other steroid
hormones produced by the body.  All the steroid hormones have a similar structure
because they are all made from cholesterol, hence the derivation of the term steroid from
cholesterol.  Cholesterol is normally a constituent of the cell membrane and helps the
waxy oils of the membrane become more fluid. Because of this, all the steroid hormones
can cross cell membranes relatively easily. In fact, the receptors for steroid hormones are
located inside the cell. So steroid hormones must dissolve across the cell membrane and
enter the cell to have their effects.
   While the testes are the main source of the primary male sex hormone, testosterone, and
the ovaries are the main source of the primary female sex hormone, estrogen (or
estradiol) in women, each gonad produces small trace amounts of the other sex hormone
during synthesis because of their chemical similarity.  So, males also have a small amount
of estrogen and females also produce a small amount of testosterone.  However, even in
women these small amounts of testosterone are important.  For instance, in both genders,
armpit and pubic hair are dependent upon testosterone.  The other steroids are produced
by the adrenal glands. They include the stress hormone, cortisol (a glucocorticoid), and
the salt/water balance regulating hormone, aldosterone (a mineralocorticoid).  In both
genders the adrenals also produce trace amounts of testosterone and estrogen because of
their chemical similarity to cortisol and aldosterone. 
 
After Fertilization
   There is a dynamic interplay of factors which lead to a cascade of events that
differentiate a male from a female that occur after a sperm fertilizes an egg.  One thing to
keep in mind is that the male pattern of development requires things to occur.  It is, in a
sense, a much more active process that the female pattern of development. The female
pattern is basically the default pattern for an embryo or fetus. At the cell level, whenever
there is not an explicit "order" issued, development progresses according to the female
pattern.
   When an ovum is fertilized by a sperm with a Y chromosome, a gene called SRY (for
sex-determining region Y) on the Y chromosome will be activated and begin production
of a hormone called testes determining factor (TDF). TDF causes the primordial gonad,
the undifferentiated gonadal tissue, to become testes. Without TDF, the gonad would have
become ovaries by default.  Once the testes are formed they produce two hormones,
testosterone and Mullerian inhibiting factor (MIF).  Testosterone nourishes and promotes
the development of the Wolffian system while MIF actively causes the Mullerian system
to deteriorate.  The external genitalia are then masculinized by testosterone or more
readily by its metabolite, dihydrotestosterone (DHT), which is a much more potent binder
of the testosterone receptor.  The enzyme 5-alpha-reductase converts testosterone to
DHT.  Ironically, however, the brain is masculinized by testosterone only after it is
converted to estrogen within the cells of the brain by the enzyme aromatase. To prevent
inadvertent masculinization of the brain by maternal estrogen, all embryos and fetuses
produce an estrogen binding protein called alpha-fetoprotein which captures any
estrogens it comes in contact with. Testosterone is unaffected by alpha-fetoprotein. It
enters the brain cells and is converted into estradiol within the neurons.  As far as the
body is concerned simple sexual differentiation is basically complete at this point.  The
secondary sex characteristics will be finalized during the sex hormone surges during
puberty.
 
When Things Go Wrong
   There are numerous things that can go wrong with sexual differentiation.  There can be
problems at any of the levels: genetic, gonadal, external genitalia and internal genitalia. 
We'll examine some of the more notable cases.
   In Klinefelter's syndrome, the individual is an XXY male (sometimes called 47-XXY). 
Now, there are cases of XXY males without Klinefelter's (about 20% of them seem to
escape the disorder) but all Klinefelter's patients are XXY males. As children,
Klinefelter's males may have reduced muscle strength, but they grow they catch up
though they may have reduced muscular coordination.  As they mature past puberty and
into adulthood, they are often taller than average, but often thin, less muscular sometimes
show breast development and are infertile.  While they may seem to have slightly below
normal intelligence this is likely due to an increased rate of language problems (both
generating and processing language as well as reading problems) which make testing
more difficult.
   In Turner's syndrome, the individual has only one sex chromosome, an X (sometimes
referred to as a 45-X0) and since there is no Y chromosome the individual is a female. 
Turner's women tend to be shorter than average and are usually infertile because of a lack
of ovary function. These individuals also often have extra skin on the neck (webbed
neck), a broad chest with widely spaced nipples, puffiness/swelling of the hands and feet,
skeletal abnormalities, heart defects and kidney problems.  They are of normal
intelligence with good verbal skills and reading skills; however, many have problems
with math, memory skills and fine-skilled finger movements.
   Androgen Insensitivity syndrome (AIS; sometimes referred to by the older term,
testicular feminization) refers to a condition where a genetic XY male develops
phenotypically (mostly) as a female due to inoperative testosterone receptors.  However,
the Y chromosome led to the development of testes which produce testosterone and MIF.
While the body tissues do not respond to testosterone and develop as female by default,
the MIF causes the Mullerian system to deteriorate and these individuals have no uterus,
fallopian tubes and deepest third of the vaginal canal. Hence these individuals, while
appearing externally to be normal females will be infertile. This disorder is typically not
apparent until puberty because of a lack of menstruation and underarm and pubic hair.
   5-alpha-reductase deficiency is a very rare condition (only reported in isolated
populations in the Dominican Republic, New Guinea and Turkey) of genetic XY males
with a poorly functioning enzyme which converts testosterone into the far more potent
DHT.  Individuals are often born with external genitals that look female and are raised as
females.  However, the massive surge of testosterone at puberty then triggers the final
masculinization of the external genitalia and the descent of the testes. Hence, the
common name given to the condition in the Dominican Republic, heuvodoces, which is
Spanish for "eggs at twelve."  These individuals are typically infertile and may need
surgery to relocate the urethra.
 
II. Neural Development
   Questions of sexual differentiation aside, before birth and during early life the brain
continues its development.  Our experience shapes our neural architecture as our neurons
process the sensory qualities of our experiences and respond to them.
 
Neuronal Survival
   Before birth the brain has more neurons than it will have after birth.  The survival of
neurons is determined by their activity. It literally is a case of "use it or lose it."  Neurons
that make enough functional connections with other neurons are provided with growth
factors, hormones that are trophic (sustaining health and vitality), by their target neurons.
Neurons that do not make enough functional connections with other neurons go through a
programmed cell death process called apoptosis.
 
Early Experience & Fine Tuning Synapses
   After birth the size of the brain will increase but that increase is due to increases in the
size of the surviving neurons as well as increases in the number of their connections and
the dendrites and terminal buttons where they are made. There are also increases in the
number and size of glial cells.  The laboratories of Mark Rosenzweig in the 1960s and
William Greenough in the 1970s showed that rats raised from puphood in enriched
environments (large complex environments with playmates, a changing variety of toys
and structures allowing for climbing and running) had larger, heavier brains rats raised in
typical laboratory cages with limited opportunities for play, exploration, physical activity
and social interaction. The primary source of the increase was in the outer layer of the
cortex, the molecular layer, where connections are made between different distant
regions of the cortex.  These enriched environment animals also learn problems quicker
than rats raised in non-enriched environments.  As in the case of use it or lose it with
regard to neuronal number, the enhanced connections also are dependent on sustained
use. If enriched environment rats are removed from that environment their brains do lose
connections but they still wind up with more than rats that were always raised in the
typical cage.  Also the effects of enhanced connections are greatest when the enriched
environment is experienced from birth. However, modest increases are still possible when
a typical non-enriched environment adult rat is placed in an enriched environment.
   Complex early experience is not only necessary for enhanced cognition but it is also
necessary for the proper wiring of the sensory processing parts of the brain.  Not only is it
necessary, but there are critical periods, especially sensitive time frames where the
experience must be had or else the proper wiring of the sensory areas will never be
accomplished.  In the 1960s and 1970s, the work of Nobel Prize winners David Hubel
and Torsten Wiesel in cats showed that in the first six weeks of a cat's life if the visual
cortex is deprived of the proper sensory stimulation from the eyes, the cortex will never
be able to properly process visual information.  The brain requires early experience to
properly wire the cortex and there's a bit of a time deadline to do the job. In humans,
critical periods seem to exist not only for sensory processing but also for such things as
language, math, music and other cognitive skills and traits.  However, the critical periods
are not narrowly or well-defined as in cats.  However, the ability to flexibly wire the
brain seems to decrease after puberty starts.
 
III. The Psychology
   In contrast and in concert with the biological basis of development, psychological
development also seems to proceed in stages. Jean Piaget (1896-1980) was the originator
of the stage theory of childhood cognitive development. While not complete in its original
form, like Freud he started a field that owed much to his raising basic theoretical
questions.  For Freud, it was the role of the unconscious. For Piaget, it was stages of
cognitive development; that children were not really learning like little adults.  His
conceptual breakthrough came while he was working for Binet and Simon on the
development and refinement of intelligence testing. While grading them he noticed that
young children consistently gave wrong answers to certain types of questions.  They kept
making kept making the same pattern of mistakes that were different than those of older
children and those of adults.
 
Cognitive Development
   Piaget's theory proposes four stages and the processes by which children develop
through them. The four stages are:
Sensorimotor stage (birth - 2 years old): The child interactions with the world and builds
a set of concepts about it and how it works. This is the stage where a child does not know
that physical objects remain in existence even when out of sight (object permanence).
Preoperational stage (ages 2-7): The child is not yet able to think abstractly and needs
concrete examples and physical situations. The child also has difficulty taking the view
point of others. Usually fails at conservation (the realization that the core properties
objects or sets of objects stay the same even when they are superficially changed about or
made to appear different).
Concrete operations (ages 7-11): As their experience grows, the child starts to
conceptualize, creating logical structures that explain his or her world more completely.
Conservation appears. Abstract problem solving is now possible at this stage.
Formal operations (beginning at age 11 and up): By this point, the child's cognitive
structures are like those of an adult and include advanced conceptual reasoning. Abstract
thinking is commonplace.
Piaget outlined several principles for building cognitive structures. During all
developmental stages, the child experiences his or her environment using whatever
mental constructs he or she has developed. If the experience is a familiar one or similar to
a previous experience, it fits easily (is assimilated) into the child's cognitive framework
without changing it. If the experience is different or new, the child alters his or her
cognitive structural framework to accommodate the new information. This way, the child
constructs more and more complex and accurate cognitive structures to explain and
organize their experience of the world around them.
 
Personality & Social Development
   During development, a child's personality and social skills also progress just as their
brains and cognitive skills.  Temperament is the emotional traits that organize the child's
view of the world. They are critical in the development of the child's personality. These
traits also determine how the child goes about learning about the world around him.
Temperament appears to be relatively stable from birth.  These characteristics are
themselves never "good" or "bad." How they are received by others determines whether
they are perceived by the child as being a bad or good thing. When there is an
understanding of a child's temperament, then parenting can be more effective. For
instance, some children are noisier than others, some may be more easily startled than
others. When parents understand how their child innately responds under certain
conditions, difficulties for the child can be anticipated and the child can prepared to cope
or deal with the situation. While temperament is stable during childhood, especially the
first five years of life, temperament changes do occur by adulthood.  Childhood and adult
temperament are positively correlated, but not highly (r=0.3).  However, some adults may
regress to their childhood temperaments under times of prolonged stress in their lives.
   Humans are social creatures and that is evident from early infancy.  All children, (even
the blind) begin to smile by 2 months of age and they do so initially to potentially
everybody.  However, by 7-8 months, children start to exhibit wariness, especially to
strangers. This wariness increases gradually peaking at 14-18 months of age then it
begins to gradually decrease. By the age of 3 years most children feel secure enough to
interact with other children and adults even in the absence of their parents.
   These social behaviors indicate the human need for attachment in the development of
the normal personality. The first indication of its importance came from studies in
primates by Harry Harlow. In his first experiments infant monkeys were taken from their
mothers at six to twelve hours after birth and were raised alone with access to substitute
mothers made either of heavy wire or of wood covered in terry cloth. In one experiment
both types of substitute moms were available, but only one was equipped with a nipple
for nursing. Even when the wire mother was the source of food, the infant monkey spent
a much more time clinging to the cloth mother, indicating that the infant had an innate
preference for the softness and the warmth of contact with the cloth which would have
been more similar to that of their real mother.  When they matured and were reintroduced
to other monkeys their actions were extremely unusual. They often clutched themselves
and rocked constantly back and forth and they often exhibited excessive and misdirected
aggression to other monkeys. Sexual behavior was seriously impaired.  Usually when a
female raised with inanimate substitute mothers was approached by a normal male, she
would sit unmoving, squatting upon the floor. A substitute mom male might approach a
sexually receptive female, but he might grab the head instead of the hind legs, engaging
in pelvic thrusts. Others grabbed the females sideways, rendering their reproductive
efforts in vain. The substitute mom females also failed as mothers themselves, being
either indifferent or abusive toward their offspring. The indifferent ones did not nurse,
comfort, or protect their young, but did not harm them. The abusive mothers violently bit
or otherwise injured their infants, sometimes to the point of death.  Harlow's studies
indicated that maternal care and contact are important for normal social skills to develop
as well as the ability to form emotional bonds with others. This ability to form emotional
bonds is attachment. And learning how to do this in the parent-child relationship seems to
serve as the emotional blueprint for forming general emotional attachments in all our
other relationships
   When a human infant (or monkey infant) is separated from its mother, the infant goes
through three emotional reactions in stages. First is protest, in which the infant cries and
refuses to be consoled by others. Second is despair, in which the infant is sad and
unresponsive. Third is detachment, in which the infant intentionally disregards and
avoids the parent if the parent returns.  Attachment research on human infants suggests
that sensitive responding by the parents to the infant's needs results in an infant who
demonstrates secure attachment by the infant to the parents, which is usually
demonstrated by the child's efforts to draw close to the parents or contact or at least greet
the parent at a distance with a smile or wave. A lack of sensitive responding results in an
insecure attachment by the infant. With insecure attachment, there seems to be a split into
two varieties, termed avoidant (in which the child avoids or ignores the parent) and
resistant/ambivalent (in which the child either passively or actively show hostility toward
the parent).  The attachment style is often assessed in the procedure called the strange
situation:
1. Parent and child are introduced to the toy-filled room. Parent does not participate while
the child explores.
2. Stranger enters, converses with the parent, then approaches the child.
3. First separation episode: The parent leaves inconspicuously. Stranger's behavior is
geared toward the child.
4. First reunion episode: The parent greets and comforts child while the stranger leaves
inconspicuously.
5. Second separation episode: The parent leaves again. The child is alone.
6. Continuation of second separation episode: Stranger enters and gears behavior towards
the child.
7. Second reunion episode: The parent enters, greets child; stranger leaves
 inconspicuously.
   As assessed by this procedure 60-65% of American children are securely attached,
approximately 20% are avoidant (~20%) and approximately 10% are
resistant/ambivalent. However, a new category called disorganized (10-15% of children)
has been proposed which includes children many of whom were mistreated and often had
parents in psychiatric treatment. These children seem to lack any coherent or consistent
coping style due to the erratic parenting they've received.