Below I've given you a very detailed outline. If you have read the book carefully, and study the outline carefully, you should do very well on the exam.

Don't worry about reading - Conclusion: Engineering Temperament - for the exam.

Living With Our Genes - Dean Hamer and Peter Copeland

Different lobes of the neocortex. At the rear is the occipital lobe, responsible for processing visual information. On the top (where the crown of the head is) you'll see the parietal lobe, which includes the sensory cortex area, which processes information that come in from your five senses. On the sides are the temporal lobes, which (especially in the left hemisphere) process auditory information / language. In the front (towards the left above) are the frontal lobes, which are responsible for higher-level thinking such as abstract thought and planning. The frontal lobes are also essential for your personality. The left frontal lobe controls positive feelings, the right negative. Remember what happened to Phinneas Gage.

One neuron and its connection to another neuron. At the right you can see how the "terminal buttons" are located very near the cell body of the second neuron. The first neuron will release neurotransmitters into the cerebrospinal fluid, and these neurotransmitters will influence whether or not the second neuron will "fire".

Different types of brains we see in different species. You can see that the neocortex (yellow and green) becomes much larger and more encompassing as you go "up" the phylogenetic scale.

Features of the terminal button, how neurotransmitters are released out into the cerebrospinal fluid, and how they can be absorbed into the cell body of a receiving neuron. This is how thinking takes place, and helps to explain how prescription medications (and other chemicals) influence the way the brain works.

I want to clarify the types of studies that are conducted in Behavioral Genetics:
Twin studies: can compare identical with fraternal twins on a trait; can compare twins with non-twins on a trait
Adoption studies: can compare children with their biological and adopted parents; if they are more like their biological parents, that suggests a genetic influence on a trait. We can also compare identical twins who are adopted into separate homes; if they are more similar than different, even though they are raised by separate families, that suggests a genetic influence on traits.

Robert Cloninger called this "novelty-seeking"
Exploratory excitability, impulsiveness, extravagance, disorderliness
Marvin Zuckerman called it "sensation seeking"
thrill and adventure seeking, experience seeking, boredom susceptibility, disinhibition
The other trait involved here is harm avoidance.
Novelty seeking influences work style and relationships.
The Pleasure Chemical: Dopamine
High novelty seekers need excitement for the brain to feel good.
The Nucleus Accumbens responds to Dopamine. It is the brain's "G-spot"
In human twin studies, 58% of the variability in sensation seeking is due to genes.
Behavior Genetics, twin studies, adoption studies
monozygotic, dizygotic, regular sibs
adoption studies
The Triune Brain - handout, explanation of each part
The Thrill-Seeking Gene
Richard Ebstein found that one gene, D4DR, that makes the D4 dopamine receptor.
Twin studies show novelty seeking is about 40% heritable.
But Environment also plays a role.
The Evolution of Thrills - why does this trait make sense? Novelty seeking probably adaptive, but also makes sense to have some people low on novelty seeking.
The Thrill of Love - assortive mating - birds of a feather - husbands and wives ARE more alike on novelty seeking
People who are opposite do marry, but have more problems and higher divorce rates.

Film shown 9/7-8/00 in class:  The Hijacked Brain - role of the nucleus accumbens and dopamine in addiction.

Regarding what the researchers in the film said about marijuana being addictive, like cocaine, heroine, alcohol, and methamphetamine:  (clarification from Dr. Laws) new research shows there are actually Cannabinoid receptors in the brain, suggesting that there must be a natural chemical in the brain that THC is mimicking. Also, THC may or may not be acting on the nucleus accumbens, but we know there are Cannabinoid receptors in the hippocampus (responsible for memory, which is why people forget things like their own name when high), in the cerebellum (which is why people are so uncoordinated when high), and in the hypothalamus (which controls hunger, which is why people get the munchies!). Marijuana acts differently than LSD etc. with regard to alertness; "pot" makes one sleepy, which is distinctly different than the effect caused by LSD.  Interesting stuff!

Figure I mentioned that shows destruction of neurons in monkeys after the use of MDMA, or "Ecstasy". I will be getting the original journal article on this, because what I said in class MAY not be correct; as you can see below, the caption says the animal(s) were "exposed to MDMA a year earlier" - it doesn't SAY for a whole year! So, I want to read the article to find out how many times the monkeys were exposed to the drug for such a drastic change to take place in the brain. (And how many monkeys; this just show tissue from one normal and one "drug use" monkey.) Of course there's more to this finding; it MAY be that the year follow-up looks worse than, say, two years after drug use. It may also be the case that other parts of the brain take up the slack for these areas; it may NOT be the case that just because this area of the brain is affected, other parts of the brain can't "help out" and perform the functions that might be compromised. (Source: McCann, U. D., Lowe, K. A., & Ricaurte, G. A. (1997). Long-lasting effects of recreational drugs of abuse on the central nervous system. The Neuroscientist, 3, 399-411.) See more text below after the chapter on addiction.

Low serotonin = depression

Temperamental trait called neuroticism, emotional sensitivity, harm avoidance
We know of early biological markers: fast fetal heart rate
Today, Robert Cloninger blames neuroticism on the neurotransmitter serotonin
Neuroticism = harm avoidance
Harm avoidance includes anxiety, fear, inhibition, shyness, depression, tiredness, hostility.
Also reflected in inability to control cravings and impulses.
Valerie and Rhonda- show different levels of temperament quality called inhibition.
At four months, these children looked quite similar. But at 9 months old, EEG recordings and their behaviors were different.
Right frontal lobe influences negative/shy emotions.
Left frontal lobe influences positive/outgoing emotions.
Inhibition, or harm avoidance in adults, is one of the most enduring aspects of temperament.
Studied by Jerome Kagan. Believe shyness has important roots in the Amygdala
When the amygdala is artificially stimulated in animals, they show signs of fear and agitation.
When destroyed, animals become tame and lose fear of threatening situations.
The roots of worry.
Studies have shown that about 40% of the variation in harm avoidance is explained by genes.
The rest is due to non-shared environmental experience - unique environment.
Prozac points the way.
Prozac (fluoxetine) targets Serotonin.
Milk is rich in tryptophan, which is the precursor to serotonin. Calms us down. Drinking milk before bed also suppresses dreaming.
Serotonin system is the most widespread in the brain.
Alters mood, self-perception, and behavior.
Reuptake is controlled by a special type of protein called a transporter.
The transporter is the target of prozac.
There is only one serotonin transporter, which comes from one gene.
People who attempted suicide have low levels of serotonin metabolites in spinal fluid.
Low amounts of serotonin transporter are found in depressed individuals.
The gene and personality.
Used NEO PI-R - DNA has been shown to be related to NEUROTICISM.

NEO is a 240-item questionnaire that measures 5 major personality traits: Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness

The gene is consistently associated with mild anxiety and harm avoidance, not severe.
People with the short serotonin transporter gene engage in more frequent sex - mild anxiety is associated with increased sex drive.

Low serotonin = aggression

The AMYGDALA releases neurotransmitters that make you feel angry.
The amygdala is in the LIMBIC SYSTEM.
Which part of the brain tries to control anger: CORTEX.
The best way to predict who will be violent is to see WHERE THEY LIVE (POVERTY).
This personality trait is related to harm avoidance, neuroticism, and anxiety - HOSTILITY.
IMPULSIVENESS - is related to hostility - it is a quick-trigger type of action.
Remi Cordoret's study of adopted children and their families. He found that for children with NON-PROBLEM GENES, the environment didn't matter.
For children with biological parents who had experienced trouble with the law, alcohol, or getting along with others, the children who had bad adopted environments WERE AT RISK FOR DEVELOPING PROBLEMS.
For children with "bad genes" when their environment was good, they WERE NOT MORE LIKELY TO EXPERIENCE DIFFICULTY.
Swedish study - being adopted into a high-risk family raised criminality 7%.  Being from a high-risk family and being raised by a high-risk family raised the risk of trouble to 40%.
Research shows that in EARLY CHILDHOOD, what matters most in predicting violence is the environment. Later in life what matters most is GENES.
Bad environments create bad children. But when you look at violence in adults, it is GENES that predicts violent behavior.
Why? Role models in the environment influence us more when we're young.
Goodwin studied discharged Marines. He looked at spinal fluid of marines with excessive violence, and found decreased levels of 5-HIAAA, a breakdown of SEROTONIN.
Low levels of this substance is found in other aggressive people, including children who torture animals.
Recall that Serotonin is thought to be related to anxiety, depression, hostility, and other facets of the temperamental trait known as HARM AVOIDANCE.
SEROTONIN'S job is to make people feel bad. It is the brain's punishment chemical.
Whether people are mad at themselves or others, Serotonin is involved.
Increasing Serotonin in lab animals causes them to be LESS AGGRESSIVE.
Lower levels of Serotonin increases aggressive and impulsive behavior.
In natural conditions, the most aggressive monkeys have the lowest levels of Serotonin.
Genetic engineering allowed researchers to breed a strain of mice lacking one Serotonin receptor called 5-HT1B. These mice were all males.
Normal mice react aggressively to strange males placed in their cage.
But when a normal mouse was dropped into the cage with the mutant mice, he was attacked viciously. Simply by removing one of the Serotonin receptor genes, mice were turned into crazed killers.
Low Serotonin causes aggression.
BUT, the environment can alter one's level of Serotonin. Monkeys high in a dominance hierarchy have higher levels of Serotonin. When they are placed into a new group, and are therefore lower on the hierarchy, their Serotonin levels drop.
So, applying this to humans, we understand that high stress environments can cause low levels of Serotonin.
XY sex genes and aggression.
The rate of male-to-female homicide is the same in all cultures.
XYY males are more aggressive, but they are so few of them.
Y chromosome manufactures testosterone.
In a study of US military veterans, the top 10% on testosterone had significantly increased levels of aggression. Same with hockey players.
But, we also know that experience alters levels of testosterone.
The human brain has been programmed to respond to testosterone with aggressiveness and competitiveness, and to respond to aggression and competition with increased testosterone.
The Mystery of the Murderous Mice
Solomon Snyder discovered the role of NITRIC OXIDE. He knocked out the gene for this gas in mice brains. These mice are vicious killers.
These "knockout" mice were also voracious in their sex drive.
They reasoned that nitric oxide must function as a brake on bad behavior.
Inmate X.
It was discovered that all the males in the family who were related through their mothers were highly aggressive and had low IQ scores.
These men had a gene for monoamine oxidase A, one of the enzymes that breaks down SEROTONIN.
When mice were bred with the same genetic defect, they became crazed killers.
SO THE STORY HERE IS THAT THESE BRAINS AREN'T USING SEROTONIN. Same as above - low levels of Serotonin = aggression.
Studies of Twins shows that the GENERAL parenting style, which both twins share, has little quantitative effect on aggressive behavior.
But twins are susceptible to NONSHARED experiences.
The best thing parents can do is SHOW LOVE AND AFFECTION.
The more harsh the parenting, the more aggressive behavior in children.
Negative parenting has a stonger effect than positive parenting.
Children who are abused or neglected are 42% more likely to be arrested for violence as adults.
These children lack empathy. When they see other children hurt, they often respond by inflicting more pain on the child.
But what matters most is Geography - where a person lives / grow up.
The stress of the environment.

When an addict anticipates a drug, the Nucleus Accumbens starts to release DOPAMINE.

Returning to the topic of the drug "Ecstasy"

(MDMA, 3, 4-methylenedioxymethamphetamine),

I received a copy of the following article: McCann, U. D., Lowe, K. A., & Ricaurte, R. A. (1997). Long-lasting effects of recreational drugs of abuse on the central nervous system. The Neuroscientist, 3, 399-411. Here's what this review article had to say about ecstacy, as well as other recreational drugs (and it ain't pretty):

Ecstasy is a synthetic amphetamine derivative widely used for recreational purposes. It is related to amphetamine (speed), as well as mescaline, a well-known hallucinogen. Publications regarding its use have been around since at least 1978. It was initially used by mental health specialists in a variety of controlled settings, in order to explore its effectiveness for treatment of a variety of problems (mostly in counseling settings; LSD was once hailed as a "miracle drug" by some therapists and counselors, too). In 1986, the DEA classified ecstasy as a Schedule I controlled substance (the "most dangerous" category, which also leads to longest jail terms for possession and distribution). Nevertheless, use of ecstasy has dramatically increased in the last 15 years.

No one doubts the "euphoric" and mood-enhancing qualities of using ecstasy. The problem is that it isn't a harmless drug. Here's why: In a variety of studies with a variety of species (rats, monkeys, HUMANS), the drug has been shown to affect serotonin neurons. As we've learned in this class, low levels of serotonin aren't good. MDMA is toxic to these neurons, 5-HIAA, and the serotonin transporter proteins. The type and amount of toxicity caused by MDMA is different in different species. In rodents, there is evidence of neuron regeneration. In non-human primates, there is evidence that regeneration is unsuccessful, and that the serotonin pathways are altered. Long-term toxic effects of MDMA have been documented in mice, rats, guinea pigs, and monkeys. The neurotoxic dose (meaning, that which can be toxic to the neurons) in humans is basically one administration of the drug, in its typical dose (@ 98 mg). Many human users take more than one dose per night. Of three published studies of the levels of 5HIAA (serotonin breakdown) in cerebro-spinal fluid, one study showed reductions and one did not. There are other factors that will affect levels of 5-HIAA, however. More recently, a controlled study comparing 30 MDMA users with 28 healthy controls, MDMA users were found to have approximately 30% reduction in 5-HIAA. The authors state, "These findings...raise concern that recreational MDMA use may be associated with brain serotonin neurotoxicity in humans." In addition, MDMA has been implicated in various enduring clinical neurologic and psychiatric complications. The range, duration, and severity of neuropsychiatric effects are quite variable, including neurovascular complications, memory or cognitive disturbance, psychosis, panic disorder, and major depressive disorder.

In short, if you've done it, stop. If you've never done it, don't. If you know anyone who has or might do it, please ask them to read this. I'll put a copy of the journal article on reserve in the library, under my name.

Cocaine

Long-lasting effects on the central nervous system include ischemic or hemorrhagic stroke. Long-lasting alterations in cerebral blood flow. Changes in cerebral glucose metabolism. May have dopamine neurotoxic potential. Decreases in the number of D2 dopamine receptors, and the dopamine transporter. The research on cocaine's long-term or permanent effect on the brain paints a mixed or inconsistent picture of damage.

Marijuana

Marijuana has been used for centuries for its psychoactive effects. Contains at least 400 chemicals. Studies with rodents orally exposed with THC for 3 months reveal changes in the hippocampal region (memory!). Research with monkeys finds inconsistent results regarding damage to the hippocampus. Chronic use in humans has reported to produce an amotivational syndrome characterized by apathy, dullness, memory and cognitive impairments, and loss of goal-directed behavior. However, controlled studies have failed to produce such results. Currently, the question of whether or not marijuana use can produce long-term neuropsychological damage or consequences is unresolved.

Alcohol

Alcoholism is associated with cerebral degeneration, Korsakoff's syndrome (a type of dementia), among other disorders. Long-term effects usually only develop after many years of heavy alcohol use.

LSD

Lysergic acid diethylamine (LSD) use has been associated with many lasting neuropsychiatric impairments, the most severe being chronic psychosis. Studies with rodents suggest LSD produces changes in brain serotonin systems.

Opiates

Studies of the effects of opiates in adults are not suggestive of direct neurotoxic effects on the brain. Many indirect effects have been documented, however, including stroke, encephalopathy, and loss of cells in the basal ganglia.

Summary: Of all the drugs reviewed in this article, the research shows that one-time or short-term use of ecstasy clearly produces the most serious consequences in the brain. It is likely, then, that long-term use would produce the worst consequences as well.

Limbic system
Evolution:  Sex feels REAL good - has been selected for because making a lot of humans is the best way for survival of genes.
What males are programmed to do; what females are programmed to do.
What we look for in mates.
Willingness to have casual sex - males vs. females.
Sexual differentiation - 7 weeks, 14 weeks.
Sometimes, this goes awry; John/Joan. Androgen insensitivity syndrome.
TDF – only men have it – only consistent genetic difference between sexes
Novelty-seeking – related to number of sexual partners
Correlation between D4DR gene and number of sexual partners
Gay men with long form of the D4DR gene had more sexual encounters with women
D4DR may be a "promiscuity" gene.
The D4 Dopamine receptor gene influences male sexual behavior
Prozac – works on the brain transporter Serotonin
Some people have a version of the serotonin transporter gene that acts like a natural Prozac to reduce anxiety and depression
Q: Does the natural Prozac also reduce sexual desire?
Men with the high anxiety form of the serotonin transporter gene had sex more often than those with the low anxiety form
Sexual orientation - Continuum
NIH measured attraction, fantasy, behavior, and self-identification
Women are more likely spread out on the continuum scale
Genetic linkage - 40 pairs of gay brothers - linkage on the X chromosome in region Xq28 - 33 out of the 40 pairs were the same. Second study confirmed the concordance.
Heterosexual brothers of gay men did NOT have the same markers.
Researchers have NOT found a "gay gene" and don't expect that the gene is the same in every man.
Gay men can trace their attraction back to childhood or early adolescence
Identical MALE twins just as likely to both have the same sexual orientation (50%)
NOT due to parenting style
Female sexual orientation is MORE influenced by the environment than genes
Twins of lesbians more likely to be lesbian than heterosexual offspring
No difference between Identical and Fraternal twins
Gay males are related through the maternal lineage
Daughter of a lesbian mother has a 33% chance of being lesbian

In-class discussion about the UGA study of Homophobia and arousal to sexually explicit films.

Other reasons why sexual orientation is NOT thought, by scientists, to be learned or a choice.
No reliable differences in parent-child relations, or childhood experiences (e.g., Barbie dolls, tomboy behaviors)
Most gay people had their first sexual experience with an opposite-sex person.
Attempts of therapists to change sexual orientation were by-and-large never successful.

9/22/00 The case of Clive Wearing. Viral encephalitis. LTM (implicit, explicit), awareness (LTM, current info). Memory involves encoding, storage, retrieval. Information-Processing Theory and analogy to computer.

The current trend in obesity has nothing to do with our genes and everything to do with how we live.
The world we have created is radically different than the one for which we are biologically designed.
We have separated food from hunger at a time when the supply is unlimited.
We have REVERSED what is important. It used to be important to be able to conserve calories and store fat. NOW it is important to be able to SHED calories and NOT store fat.

Fat Genes
Body weight is about 70% inherited.
No relationship between parents and their adopted children.
BUT no one is going to get fat if they don't eat more calories than they burn.
Genes are very important, but still dependent on the environment.

Key part of the brain is the hypothalamus.
The "start eating" center is located on the lateral part of the hypothalamus. It is connected to the dopamine circuit.
When destroyed, a lab rat refuses to eat. When stimulated, the rats eat even when full.

Serotonin inhibits eating of carbohydrates, but not protein or fat.
Scientists found an "obese gene" that codes for LEPTIN, an amino acid produced by fat cells.
The fatter the cell, the more leptin it produces.
Injecting pure Leptin into obese mice causes them to lose weight.
Leptin tells the brain to stop eating.
Human leptin was produced artificially and injected into mice - they lost weight.
But, when obese humans were tested, they were found to be producing more leptin than normal humans.
They found a mutation in the leptin genes in obese humans. Produces a mutation that disables the leptin gene, producing an inactive version of the protein.
But the leptin mutation is very rare - can't account for most of human obesity.
A study of twins in Finland discovered that obese humans had higher levels of leptin.
In dieting people, leptin levels fall.
Then a leptin receptor gene was found in the hypothalamus.
Thus, the leptin receptor must send signals to the brain to decrease hunger and to the body to increase metabolism.

Metabolism
People who are overweight also burn calories slowly.

Supertasters and Nontasters.
Supertasters tend to be thinner and have lower cholesterol. They don't enjoy eating what's not good for them.

Emotional Overeating
The key is Serotonin - the same chemical involved in neuroticism, harm avoidance, aggression and hostility
Psychological hunger can only be satisfied by eating foods that supply serotonin.
We can't create a Serotonin pill - it can't pass directly from the bloodstream into the brain.
Instead, the body needs sweet and starchy carbohydrates to boost the brain's supply of tryptophan, the amino acid building block for serotonin.
Eating habits and traits such as neuroticism, harm avoidance are mediated by serotonin.

Two reasons why the average lifespan increased during the 20th century.

The body does NOT wear out due to use.
We have extended our life, but not because of our genes - due to better diets and health care.
Genes are SELECTED FOR when you are reproductive (which is NOT old age). Those genes that allow you to pass on your genes are selected, not genes that specifically cause us to live a long time.

Longegity Genes
Longevity runs in families.
Age of death is closer for identical twins than fraternal. Heritability is @ 25%
MOST of the variability in how long people live is in the seemingly random factors unique to each individual and not shared with the family.
Probably 70% of the 100,000 human genes are involved in longevity.

Michael Rose's research with fruit flies strongly suggest there a lots of genes that influence longevity. If there were just a few, his fruit flies would not continue to live longer than recent generations, since he's been breeding the flies since 1976.

Body Rust
Cells use oxygen every day. Not all oxygen is good. Forms of oxygen that contain an unpaired electron, called a free radical, are among the most destructive toxins in the body.
They attach themselves to many different types of molecules, looking for a home.
They damage the cellular molecules to which they attach themselves.
When free radicals attack our cells, it is called aging.
age-1 genes in worms - shown to be protective against free radicals

Werner's syndrome - fast aging in humans - chromosome 8 - helicase, an enzyme that unwinds the double-helical DNA molecule - "ladder" can't unwind in people with Werner's syndrome - also, tips of chromosomes are worn off faster - telomeres

Hutchinson-Gilford syndrome (Progeria) - only about 30 known sufferers in the world - victims die before age 20 - telomere shortening is quickened

As we age, the tips of our chromosomes, called telomeres, break off with each cell replication.
When we reach the end of the telomeres, our cells can't replicate any more.
The limit seems to be 50 cell divisions.
Biotechnology companies are now in a race to produce Telomerase, the enzyme that allows the telomeres to retain their length on chromosomes. The problem is that telomerase is also prominent in cancer cells (which is why cancerous tumors simply keep on growing).
Even if we could make cells divide beyond the limit of 50, this doesn't do anything to protect the brain cells. They don't divide and replicate, but they do suffer from the aging process (e.g., from free radicals). So, we might have a very healthy body at age 140 but a deteriorated mind.

Alzheimer's Disease
It is just ONE of the mental diseases we call dementias.
The brains of people with Alzheimer's disease lose neurons much faster than people without the disease. Neuron loss is particularly devastating in the hippocampus, which is the brain region most important for making new memories.
Cell death in Alzheimer's patients takes the form of amyloid plaques and neurofibrillary tangles.
Having two copies of the gene that creates apoE4, a protein that sticks to the plaque-causing beta-amyloid, means a person has a 3-5 times higher chance of developing Alzheimer's disease.
But, even with the strong evidence, many people with the "bad" gene don't get Alzheimer's, and lots of people without the gene do get Alzheimer's.

The Soul Gene
Costa & McCrae - personality changes little after age 30 - we've done what we came here to do; settle back into our genetic instructions