15Abnormal Psychology Disorders and Treatment© 2019 Cen

15
Abnormal Psychology: Disorders and Treatment
© 2019 Cengage. All rights reserved.
1
module 15.1
An Overview of Abnormal Behavior
After studying this module, you should be able to:
Describe and evaluate a definition of mental illness.
Define the biopsychosocial model of mental illness.
Give examples of cultural influences on abnormal behavior.
Describe DSM-5 and give examples of the categories it lists.
Evaluate the assumptions behind DSM and the categorical
approach to mental illness.
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Defining Abnormal Behavior
The American Psychiatric Association defines mental disorder
as a clinically significant disturbance in an individual’s
cognition, emotion regulation, or behavior.
It is sometimes difficult to apply that definition, because of
disagreements over what constitutes a significant disturbance.
In the past, people have described abnormal behavior in many
ways, including spirit possession.

The Biopsychosocial Model
Biopsychosocial model – concept that emphasizes biological,
psychological, and sociological aspects of abnormal behavior
Cultural Influences on Abnormality
A culture provides examples not only of how to behave
normally but also of how to behave abnormally.
The American Psychiatric Association defined mental disorder
as a “clinically significant disturbance in an individual’s
cognition, emotion regulation, or behavior that reflects a
dysfunction in the psychological, biological, or developmental
processes underlying mental functioning.” That seems a
reasonable definition, but it is not always easy in practice. Who
decides whether someone has a clinically significant
disturbance? Do we let people themselves decide? Do we always
trust a psychiatrist or psychologist to decide? What if therapists
disagree with one another?
In previous eras, people have held many views of abnormal
behavior and its causes. The idea of demon possession was
popular in medieval Europe and is still common in much of the
world today.
The ancient Greeks explained behavior in terms of four fluids:
An excess of blood caused a sanguine (courageous and loving)
personality. An excess of phlegm caused a phlegmatic (calm)
personality. Too much yellow bile made one choleric (easily
angered). Too much black bile made one melancholic (sad).
In traditional Chinese philosophy, personality cycles through
five stages or elements, just as the seasons do. An excessive
response could cause too much fear, anger, and so forth.

The standard view today is that abnormal behavior results from
a combination of biological, psychological, and social
influences.
The biological roots of abnormal behavior include genetic
factors, infectious diseases, poor nutrition, inadequate sleep,
drugs, and other influences on brain functioning.
The psychological component includes reactions to stressful
experiences. For example, people who were physically or
sexually abused in childhood are more likely than others to
develop psychological problems in adulthood.
Also, behavior must be understood in a social and cultural
context. Behavior that is considered acceptable in one society
might be labeled abnormal in another. For example, loud
wailing at a funeral is expected in some societies, but not in
others.
We learn from our culture how to behave normally. We also
learn some of the options for behaving abnormally.
3
DSM and the Categorical Approach
to Psychological Disorders (slide 1 of 2)
To standardize their definitions and diagnoses, psychiatrists and
psychologists developed the Diagnostic and Statistical Manual
of Mental Disorders (DSM).
Diagnostic and Statistical Manual of Mental Disorders (DSM) –
a reference book that sets specific criteria for each
psychological diagnosis
The latest edition of the Diagnostic and Statistical Manual of
Mental Disorders (DSM-5) lists possible diagnoses and the

criteria for identifying each of them.
4
Table 15.1 Categories of Psychological
Disorders According to DSM-5Neurodevelopmental
DisordersSchizophrenia SpectrumBipolar and Related
DisordersDepressive DisordersAnxiety DisordersObsessive-
Compulsive DisordersTrauma-Related DisordersDissociative
DisordersSomatic Symptom DisordersEating
DisordersElimination DisordersSleep-Wake DisordersSexual
DysfunctionsGender DysphoriaImpulse Control
DisordersSubstance Abuse and AddictionsNeurocognitive
DisordersPersonality DisordersParaphiliasOthers
Table 15.1 shows the categories of disorder, as listed in DSM-5.
5
DSM and the Categorical Approach
to Psychological Disorders (slide 2 of 2)
Criticisms of the categorical approach:
Most troubled people partly fit two or more diagnoses.
The genetic and environmental causes of various disorders
overlap.
The treatment designed for one disorder may help with another.
Too many conditions are labeled as “mental illnesses.”
An alternative is to rate each person along several dimensions
of distress.
DSM has helped standardize psychiatric diagnoses so that
psychologists use terms like depression, schizophrenia, and so

forth in more consistent ways than they would otherwise.
However, this approach assumes that every disorder fits into
one category or another, and that each troubled person can
receive a single, unambiguous diagnosis. In fact, many troubled
people fit several diagnoses partly and none of them perfectly.
If you are suffering from depression, mania, anxiety, substance
abuse, conduct disorder, obsessive-compulsive disorder, or
schizophrenia, the chances are better than 50/50 that you are
suffering from one or more of the others also, at least to a mild
degree. You might fit mainly into one diagnosis now but a
different one later. Furthermore, different disorders have many
overlapping causes. The genes that increase the risk of any one
disorder also increase the risk of other disorders. Highly
stressful experiences, such as the sudden death of a loved one,
can trigger the onset of depression, anxiety, or schizophrenia.
Even when therapists agree on a single diagnosis, the diagnosis
doesn’t reliably point the way to a treatment. Antidepressant
drugs sometimes help people with disorders other than
depression, and antipsychotic drugs sometimes help relieve
nonpsychotic disorders.
Many psychologists who are dissatisfied with the DSM
approach would prefer to rate each client’s problems along
several dimensions, instead of trying to give each person a
label. For example, instead of a single diagnosis, a therapist
might use ratings like the one shown on this slide.
A further criticism is that DSM labels too many conditions as
“mental illnesses.” If you seek help to increase your enjoyment
of sex, you have sexual interest/arousal disorder or hypoactive
sexual desire disorder. A woman with premenstrual distress gets
a diagnosis of premenstrual dysphoric disorder. If you get at
least seven hours of sleep per night but still feel sleepy during
the day, and you have trouble feeling fully awake after a sudden
awakening, you have hypersomnolence disorder. The list goes
on, with hundreds of other possibilities. Surveys have found

that almost half of all people in the United States qualify for at
least one DSM diagnosis of mental illness at some time in life.
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Figure 15.2
◄ Figure 15.2 In this survey, just over one-fourth of U.S. adults
suffer a psychological disorder in any given year, and nearly
half do at some time in life. (Based on data of Kessler,
Berglund, et al., 2005; Kessler, Chiu, et al., 2005)
The most common disorders are anxiety disorders, mood
disorders (e.g., depression), impulse control disorders
(including attention deficit disorder), and substance abuse, as
shown in Figure 15.2.
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module 15.2
Anxiety Disorders and Obsessive-Compulsive Disorder
Describe generalized anxiety disorder and panic disorder.
Explain why learned avoidance responses are so resistant to
extinction.
Describe theoretically how classical conditioning could explain
the onset of a phobia.
Evaluate the limits of the classical conditioning explanation of
phobia, citing observations that it does not easily explain.
Describe obsessive-compulsive disorder.
Explain how therapists treat phobias and obsessive-compulsive
disorder.

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Disorders with Excessive Anxiety
Generalized Anxiety Disorder (GAD)
Generalized anxiety disorder (GAD) – disorder in which people
have frequent and exaggerated worries
Panic Disorder (PD)
Panic disorder (PD) – condition marked by frequent periods of
anxiety and occasional attacks of panic—rapid breathing,
increased heart rate, chest pains, sweating, faintness, and
trembling
Panic disorder is linked to having strong autonomic responses,
such as rapid heartbeat and hyperventilatio n.
Hyperventilation – rapid deep breathing
Many people with panic disorder develop agoraphobia or social
phobia.
Agoraphobia – an excessive fear of open or public places
Social phobia – a severe avoidance of other people and a fear of
doing anything in public
People with generalized anxiety disorder experience excessive
anxiety much of the day, even when actual dangers are low.
Panic disorder is characterized by episodes of disabling anxiety,
high heart rate, and rapid breathing. Several studies have shown
a genetic contribution, although no single gene has a strong
influence. Many people with panic disorder also develop
agoraphobia, an excessive fear of open or public places, or
social phobia, a severe avoidance of other people and a fear of
doing anything in public. The usual treatment focuses on
teaching the patient to control breathing and learning to relax.
Controlling stress helps also.
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Phobia
Avoidance behaviors are highly resistant to extinction.
Phobia – a fear that interferes with normal living
Phobias are learned through observation as well as through
experience.
Avoidance behaviors are highly resistant to existence. For
example, if you believe that Friday the 13th is dangerous, you
are cautious on that day. If nothing goes wrong, you decide that
your caution was successful. If a misfortune happens anyway, it
confirms your belief that Friday the 13th is dangerous. As long
as you continue an avoidance behavior, you never learn whether
or not it is useful.
A phobia is a fear that interferes with normal living. Many
people develop phobias through traumatic experience. They also
learn their phobias by watching others.
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Some Phobias Are More Common than Others
Common objects of phobias include:
Public places
Public speaking
Heights
Air travel
Water travel
Being observed by strangers
Snakes or other dangerous animals
Blood
Lightning storms
People develop fears of some objects more readily than other
objects.
People may be born with a predisposition to learn fears of

objects that have been dangerous throughout our evolutionary
history.
We more readily fear objects with which we have few safe
experiences and objects that we cannot predict or control.
Common objects of phobias include public places, public
speaking, heights, air travel, water travel, being observed by
strangers, snakes or other dangerous animals, blood, and
lightning storms. Social phobia—avoidance of contact with
unfamiliar people—is also common.
People are more likely to develop phobias of certain objects
(e.g., snakes) than of others (e.g., cars). The most common
objects of phobias have menaced humans throughout
evolutionary history. They pose dangers that are difficult to
predict or control, and we generally have few safe experiences
with them.
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Treatment for Phobias
The most successful type of therapy for phobia is exposure
therapy, also known as systematic desensitization.
Exposure therapy (or systematic desensitization) – a method of
reducing fear by gradually exposing people to the object of their
fear
In systematic desensitization, the patient is prevented from
fleeing the feared stimulus.
He or she learns the danger is not as great as imagined.
Although exposure therapy is highly effective, at least
temporarily, phobias sometimes return.
A common therapy for phobia is exposure therapy, also known

as systematic desensitization. The patient relaxes while being
gradually exposed to the object of the phobia. For example,
someone with a phobia of snakes is exposed to pictures of a
snake in the reassuring environment of a therapist’s office. The
therapist might start with a cartoon drawing and gradually work
up to a black-and-white photograph, a color photograph, and
then a real snake. The client is terrified at first, but the
autonomic nervous system is not capable of sustaining a
permanent panic. Gradually, the person becomes calmer and
learns, “It’s not that bad after all. Here I am, not far from that
horrid snake, and I’m not having a heart attack.”
Although exposure therapy is highly effective, at least
temporarily, phobias sometimes return. Exposure therapy is
extinction of the original learning, but extinction is merely a
suppression of original learning, not an erasure of it. When time
passes after an extinction procedure, spontaneous recovery is
likely—that is, a return of the original learned response.
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Obsessive-Compulsive Disorder (slide 1 of 2)
Obsessive-compulsive disorder (OCD) – a condition with
repetitive thoughts and actions
Obsession – a repetitive, unwelcome stream of thought
Compulsion – a repetitive, almost irresistible action
Common compulsions:
Cleaning
Checking
Counting
Hoarding
People with obsessive-compulsive disorder have distressing
thoughts or impulses. Many also perform repetitive behaviors.
Obsessions generally lead to compulsions, as an itching

sensation leads to scratching. For example, someone obsessed
about dirt and disease develops compulsions of continual
cleaning and washing.
The most common compulsions are cleaning and checking.
Another common one is counting one’s steps, counting objects,
or counting almost anything. Hoarding is another common
compulsion.
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Obsessive-Compulsive Disorder (slide 2 of 2)
Distrusting Memory
Compulsive checkers constantly double-check themselves and
invent elaborate rituals.
Repeatedly checking something leads to decreased confidence
in the memory of having checked it.
Therapies
The most effective treatment is exposure to the source of
distress while preventing the ritualized response.
However, this treatment is often ineffective, partly because
many patients refuse or quit the treatment.
A valuable supplement is a cognitive intervention to help people
reinterpret their thoughts and images.
People with obsessive-compulsive disorder, especially those
who are compulsive checkers, distrust their memory. Because
they distrust their memory, they check again and again.
The therapy best supported by the evidence is exposure therapy
with response prevention: The person is simply prevented from
performing the obsessive ritual. For example, someone might be
prevented from cleaning the house or checking the doors more
than once before going to sleep.

However, although exposure therapy is the most successful
procedure currently available, it is often ineffective. People
with OCD dislike the idea of stopping their rituals, and almost
half quit the treatment without achieving any benefits. Many
people respond well to a cognitive intervention to help them
reinterpret their thoughts and images. In some cases,
antidepressant drugs also help.
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module 15.3
Substance-Related Disorders
Define substance dependence or addiction.
Explain why it is difficult to list what substances are or are not
addictive.
Discuss possible explanations for addiction.
Describe a procedure to identify young people who may be at
increased risk of alcohol abuse.
Describe treatments for alcoholism and opiate abuse.
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Substance Dependence (Addiction)
Dependence (or addiction) – inability to quit a self-destructive
habit
Addictive substances stimulate dopamine synapses in the
nucleus accumbens, a brain area that is associated with
attention.
After people develop a compulsive habit of gambling, video
game playing, or other activities, those activities also elicit
dopamine release in the nucleus accumbens.
It is hard to put limits on what can or cannot be an addictive

substance.
What Motivates Addictive Behavior?
People with an addiction continue a habit even though they
recognize that it does them more harm than good.
Reasons for continued use include avoiding withdrawal
symptoms and coping with distress.
Also, addictive substances alter the brain’s synapses to increase
response to substance-related experiences and decrease response
to other activities.
People who find it difficult or impossible to stop using a
substance are said to be dependent on or addicted to it.
Almost all addictive drugs increase the release of dopamine in a
small brain area called the nucleus accumbens, which is
apparently critical for attention and reinforcement.
However, beware of assuming that the release of dopamine in
the nucleus accumbens causes addiction. For example,
compulsive gambling and video game playing have much in
common with drug addictions. After they have become
addictive, they release dopamine in the nucleus accumbens, but
it would be misleading to say they became addictive because
they release dopamine.
It is hard to put limits on what can or cannot be an addictive
substance. Some people show addictions to gambling or video
games, which are not substances at all. Some have managed to
abuse water.
The motives for initial use of alcohol or other drugs differ from
those of addiction. People drink alcohol for pleasure, to relax,
or to suppress social anxieties. An addiction is more insistent.

Addicted drug users get much less pleasure than they used to,
but they continue to want the drug anyway. Why do addictive
behaviors continue with such intensity?
One reason is to escape unpleasant feelings. Abstaining from a
drug leads to withdrawal symptoms. Withdrawal symptoms from
prolonged alcoholism include sweating, nausea, sleeplessness,
and sometimes hallucinations and seizures. With opiate drugs,
withdrawal symptoms include anxiety, restlessness, vomiting,
diarrhea, and sweating. Consistent cigarette smokers experience
unpleasant mood when they abstain.
Also, someone who takes a drug to relieve withdrawal
symptoms learns its power to relieve distress, and then begins
using it to relieve other kinds of displeasure. People who have
quit drugs often relapse during periods of financial or social
difficulties.
Neuroscientists have demonstrated that when an addictive
behavior bombards the nucleus accumbens with massive
amounts of dopamine, it stimulates synaptic changes of the
same type that occur in learning. For example, after repeated
cocaine use, the synapses learn to respond strongly to cocaine
and reminders of cocaine, but they decrease their response to
other reinforcers. The result is a craving for cocaine and
decreased interest in most other activities. Cocaine use then
becomes the only efficient way to produce the synaptic
activities normally associated with pleasure.
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Alcoholism (slide 1 of 2)
Alcoholism – the habitual overuse of alcohol
Genetics and Family Background
A genetic predisposition contributes most strongly to early-
onset alcoholism.

Although many genes contribute in small ways, only the gene
that affects the liver’s ability to metabolize alcohol produces
effects large enough to produce results that are easily
replicated.
Alcoholism depends on the environment also.
The prevalence of alcoholism and other kinds of substance
abuse varies among cultures and subcultures.
The incidence of alcoholism is greater than average among
people who grew up in families marked by conflict, hostility,
and inadequate parental supervision.
Alcoholism is the habitual overuse of alcohol. Treating
alcoholism is difficult, and the success rate is not impressive.
A genetic predisposition contributes most strongly to early-
onset alcoholism. Late-onset alcoholism develops gradually
over the years, affects about as many women as men, is
generally less severe, and often occurs in people with no family
history of alcoholism. Early-onset alcoholism develops rapidly,
usually by age 25, occurs more often in men than women, is
usually more severe, and shows a stronger genetic basis.
Although many genes contribute in small ways, only one is
known to produce effects large enough to produce results that
are easily replicated. That gene affects the liver’s ability to
metabolize alcohol. The liver converts alcohol into a toxic
substance, acetaldehyde, and then uses another enzyme to
convert acetaldehyde into harmless acetic acid. However,
people vary in the gene for that second enzyme. Those with one
form of that gene are slow to convert acetaldehyde into acetic
acid. If they drink much at a time, they accumulate
acetaldehyde, feel ill, and experience an intense hangover.
Alcoholism depends on the environment also. The prevalence of

alcoholism and other kinds of substance abuse varies among
cultures and subcultures. For example, alcoholism is more
prevalent in Irish culture, which tolerates heavy drinking, than
among Jews or Italians, who emphasize drinking in moderation.
The incidence of alcoholism is greater than average among
people who grew up in families marked by conflict, hostility,
and inadequate parental supervision.
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Alcoholism (slide 2 of 2)
Predisposition to Alcoholism
People who have less than average intoxication from moderate
drinking are more likely than average to become heavy drinkers.
Treatments
Only an estimated 10 to 20 percent of people who try to quit
alcohol or other drugs on their own manage to succeed.
Alcoholics Anonymous (AA) – a self-help group of people who
are trying to abstain from alcohol use and help others do the
same
Antabuse – trade name for a drug alcoholics use whereby they
become sick if they have a drink
Contingency management involves providing an immediate
reinforcement for abstinence from alcohol.
One way to predict which young people will later become heavy
drinkers is to measure the amount of body sway after drinking,
or ask people to report how many drinks they need to
experience various effects. People who report experiencing
little effect from a moderate amount of alcohol are more likely
than average to become heavy drinkers.
Of all the people who try to quit alcohol or other drugs on their
own, an estimated 10 to 20 percent manage to succeed, though

many of them quit and relapse repeatedly before eventual
success. However, many other people find that they cannot quit
a substance abuse problem on their own. Eventually, they “hit
bottom,” discovering that they have damaged their health, their
ability to hold a job, and their relationships with friends and
family. At that point, they might seek help. Options include
Alcoholics Anonymous (AA), Antabuse, and contingency
management. The self-help group Alcoholics Anonymous
provides the most common treatment for alcoholism in North
America. Some alcoholics are treated with Antabuse, a
prescription drug that makes them ill if they drink alcohol.
Rewarding people for abstaining from drugs is sometimes
effective.
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Opiate Dependence
Opiate dependence generally has a more rapid onset than
alcohol or tobacco dependence.
Treatments
Some people who are trying to quit heroin and other opiates
turn to self-help groups, contingency management, and other
treatments.
For those who cannot quit, researchers have sought to find a
less dangerous substitute that would satisfy the craving for
opiates.
Methadone – a drug sometimes offered as a substitute for
opiates
Opiate dependence generally has a more rapid onset than
alcohol or tobacco dependence.
Some people who are trying to quit heroin or other opiates turn
to self-help groups, contingency management, and other

treatments. Therapists emphasize the importance of identifying
the locations and situations in which someone has the greatest
cravings, and then trying to minimize exposure to those
situations.
For those who cannot quit opiates, researchers have sought to
find a less dangerous substitute that would satisfy the craving
for opiates.
The drug methadone is sometimes offered as a substitute for
opiates. Chemically similar to morphine and heroin, methadone
can be addictive also, but it is considered a safer addiction.
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Table 15.3 Comparison of
Methadone and Morphine
MorphineMethadone
by InjectionMethadone
Taken
OrallyAddictive?YesYesWeaklyOnsetRapidRapidSlow“Rush”?
YesYesNoRelieves craving?YesYesYesRapid withdrawal
symptoms?YesYesNo
Table 15.3 compares methadone and morphine. When
methadone is taken as a pill, it enters the bloodstream gradually
and departs gradually. (If morphine or heroin is taken as a pill,
much of it is digested without reaching the brain.) Thus,
methadone does not produce the “rush” associated with injected
opiates, and therefore does not strongly interfere with important
behaviors, such as keeping a job. Methadone satisfies the
craving and blocks heroin or morphine from reaching the same
receptors. However, methadone does not eliminate the
addiction. People who try to reduce their use of methadone

generally report that their drug craving returns.
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module 15.4
Mood Disorders, Schizophrenia, and Autism
Describe the symptoms and possible causes of major depression.
Evaluate the advantages and disadvantages of several treatments
for major depression.
Distinguish bipolar disorder from major depression.
List the primary symptoms of schizophrenia.
Discuss evidence for a genetic basis of schizophrenia.
State the neurodevelopmental hypothesis of schizophrenia, and
cite evidence that supports it.
Describe therapies for schizophrenia.
Describe and discuss autism spectrum disorder.
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Depression
Major depression – condition in which someone experiences
little interest, pleasure, or motivation for weeks at a time
Nearly all people experiencing depression have sleep
abnormalities.
Depression occurs in episodes.
Although the first episode is usually triggered by a stressful
event, later episodes occur more easily.
Seasonal affective disorder (SAD) – condition in which a person
repeatedly becomes depressed during a particular season of the
year

People with depression find little interest or pleasure in life and
have trouble sleeping. Sadness is characteristic of depression,
but lack of happiness is even more characteristic.
About 20 percent of U.S. adults are depressed at some time in
life. Women experience depression more than men, and whites
experience major depression more than blacks.
Depression occurs in episodes. Typically, people have an
episode of depression that lasts a few months (less commonly,
years) and then they recover. However, the depression may
return. Later episodes tend to be briefer but more frequent.
Typically, an intensely stressful event such as divorce or the
death of a close loved one triggers the first episode of
depression, but later episodes may occur with less provocation.
In a related condition, seasonal affective disorder (SAD),
people repeatedly become depressed during a particular season
of the year. The most effective treatment for seasonal affective
disorder is exposure to a bright light for a few hours each day.
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Environmental and Genetic Influences on Depression
Research has failed to identify a gene with a major effect on
depression.
Most people with depression have relatives with depression, and
also relatives with other problems, such as substance abuse,
attention deficit disorder, and migraine headaches.
Most people recover from depression and then later develop
anxiety disorders, substance abuse, or an eating disorder.
The role of genetics with regards to depression is far from clear.
Although studies of twins and relatives of patients with
depression indicate a moderate degree of heritability, extensive

research on the chromosomes of thousands of people failed to
identify a gene with a major effect. Perhaps many uncommon
genes are capable of leading to depression, or perhaps the
explanation lies with epigenetics instead of chromosomal
changes.
Most people with depression have relatives with depression, and
also relatives with other problems, such as substance abuse,
antisocial personality disorder, attention deficit disorder,
bulimia nervosa, migraine headaches, asthma, arthritis, and
others. Many people recover from depression and then later
develop anxiety disorders, substance abuse, or an eating
disorder. In other words, the genes or other factors that
predispose to depression increase vulnerability to many
disorders, not just depression.
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Treatments for Major Depression (slide 1 of 3)
Antidepressant Medications
Three common classes of antidepressants:
1. Tricyclic drugs – drugs that interfere with axons’ ability to
reabsorb the neurotransmitters dopamine, norepinephrine, and
serotonin after releasing them
2. Selective serotonin reuptake inhibitors (SSRIs) – drugs
that block reuptake of only serotonin
3. Monoamine oxidase inhibitors (MAOIs) – drugs that block
the metabolic breakdown of dopamine, norepinephrine, and
serotonin
Although antidepressants affect the synapses within an hour or
so, their behavioral effects begin after two or three weeks of
treatment.
Perhaps they produce their benefits by enhancing cell growth in
the hippocampus.

The common treatments for depression are antidepressant
medications and psychotherapy.
Three common classes of antidepressants are tricyclics,
serotonin reuptake inhibitors, and monoamine oxidase
inhibitors. Tricyclic drugs interfere with the axons’ ability to
reabsorb the neurotransmitters dopamine, norepinephrine, and
serotonin after releasing them. Thus, tricyclics prolong the
effect of these neurotransmitters at the synapses. Selective
serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, trade
name Prozac) have a similar effect, but block reuptake of only
serotonin. Monoamine oxidase inhibitors (MAOIs) block the
metabolic breakdown of dopamine, norepinephrine, and
serotonin by the enzyme monoamine oxidase (MAO). Thus,
MAOIs also increase the effects of these neurotransmitters.
Psychiatrists seldom prescribe MAOIs except for patients who
did not respond to the other drugs.
Antidepressant drugs alter synaptic activity within an hour or
so, whereas mood improvement begins two to three weeks later.
Prolonged use of antidepressants increases production of a
chemical called BDNF (brain-derived neurotrophic factor) that
over a period of weeks leads to the birth of new neurons in the
hippocampus, expansion of dendrites, and improved learning.
(Depression is associated with impaired learning and decreased
cell growth in the hippocampus.) Those changes in the
hippocampus may be the main reason for how antidepressants
help, although researchers are not yet certain.
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Depressed Cognition and Cognitive Therapy
Cognitive therapy focuses on changing people’s thoughts and
encouraging a more active life.
Effectiveness or Ineffectiveness of Treatments

About one-third of patients recover from depression
spontaneously within a few months.
Of patients receiving psychotherapy, antidepressant drugs, or
both, a little over half recover.
For people with mild to moderate depression, antidepressant
drugs apparently produce no more apparent benefit than
placebos.
The drugs show a significant benefit for people with severe
depression, who do not respond well to placebos.
Cognitive therapy focuses on changing people’s thoughts and
encouraging a more active life. According to Aaron Beck, a
pioneer in cognitive therapy, depressed people are guided by
thoughts that he calls the “negative cognitive triad of
depression”:
I am deprived or defeated.
The world is full of obstacles.
The future is devoid of hope.
People who have these “automatic thoughts” interpret
ambiguous situations to their own disadvantage. Therapists try
to overcome these thoughts and get clients to reinterpret events
in a more positive way. A therapist might invite the client to
regard the negative thoughts as charges by a prosecuting
attorney, and then act as the defense attorney to produce
counterarguments.
Cognitive therapists also encourage people to become more
active—to take part in more activities that might bring pleasure
or a sense of accomplishment.
Because depression occurs in episodes, most people with no
treatment at all generally improve, given enough time, and some
improve within a short time. Giving a placebo increases the

chance of recovery, just by the expectation of improvement. If
we look at results a few months after the onset of depression,
about a third of patients improve with no treatment or a
placebo, and about half improve with either antidepressant
drugs or psychotherapy.
People with mild to moderate depression respond about as well
to placebos as they do to the drugs. The drugs are better than
placebos for people with severe depression, mainly because
those people don’t respond well to placebos.
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Choosing between Psychotherapy and Antidepressant Drugs
Antidepressants are convenient and less expensive than
psychotherapy, but psychotherapy’s effects are more likely to
produce long-lasting benefits.
Electroconvulsive Shock Therapy
Electroconvulsive therapy (ECT) – a treatment in which a brief
electrical shock is administered across a patient’s head to
induce a convulsion
Electroconvulsive therapy is administered today only with the
patient’s informed consent.
ECT is given in conjunction with muscle relaxants and
anesthetics to minimize discomfort.
ECT produces faster benefits than psychotherapy or
antidepressant drugs, but its benefits are the least enduring.
Other Treatments
Exercise and seafood help to prevent depression.
Antidepressant drugs usually show benefits a little faster. They
are less expensive, and it’s easier to take a pill than to spend an

hour with a therapist. However, the drugs produce unpleasant
side effects, such as dry mouth, difficulty urinating, or
increased blood pressure. Also, many people find that after they
stop taking the drugs, their depression returns within a few
months. The benefits of psychotherapy usually last longer after
the end of therapy.
For the many people who do not respond to drugs or
psychotherapy, electroconvulsive therapy (ECT) is another
option. ECT, widely used in the 1940s and 1950s, fell out of
favor because of its history of abuse. Some patients were
subjected to ECT hundreds of times without informed consent,
and sometimes, ECT was used more as a punishment than a
therapy. ECT is now used only after patients have given their
informed consent. The shock is less intense than previously, and
the patient is given muscle relaxants to prevent injury and
anesthetics to reduce discomfort.
ECT produces faster benefits than psychotherapy or
antidepressant drugs, but its benefits are the least enduring.
Although it has a high success rate for patients who did not
respond to other treatments, only about 10 percent of hospitals
in the United States offer it.
Animal research has shown that steady, nonstrenuous exercise
increases neuron formation in the hippocampus, known to be an
important part of recovery from depression. The best study with
humans showed that an increase in physical activity predicts a
lower probability of later depression, and depression predicts a
decrease in physical activity.
Seafood contains omega-3 fatty acids that are important for
brain functioning. People who eat at least a pound of seafood
per week have a decreased probability of mood disorders.
Placebo-controlled studies have confirmed the value of omega-3
fatty acids for relieving depression.

26
Bipolar Disorder
Bipolar disorder – a condition previously known as manic-
depressive disorder, in which someone alternates between mood
extremes
Mania – a condition, the opposite of depression, in which
people are constantly active, uninhibited, and often irritable
People with bipolar disorder alternate between periods of
depression and periods of mania.
27
Schizophrenia (slide 1 of 3)
Schizophrenia – a condition marked by a prolonged
deterioration of daily activities such as work, social relations,
and self-care, and some combination of hallucinations,
delusions, disorganized speech and thought, movement disorder,
and loss of normal emotional responses and social behaviors
The symptoms must include at least one of the first three
(hallucinations, delusions, and disorganized speech and
thought) and at least two of the five overall.
Hallucinations – perceptions that do not correspond to anything
in the real world
Delusion – belief that is strongly held despite evidence against
it
A diagnosis of schizophrenia applies if someone has
deteriorated in everyday functioning and shows other symptoms
from this list: hallucinations, delusions, disorganized speech
and thought, movement disorder, and loss of normal emotional
responses and social behaviors. The symptoms must include at

least one of the first three (hallucinations, delusions, and
disorganized speech) and at least two of the five overall.
Hallucinations are perceptions that do not correspond to
anything in the real world, such as hearing voices that no one
else hears. The voices may speak nonsense, or they may direct
the person to do something. People sometimes think the voices
are real, sometimes they know the voices are unreal, and
sometimes they are not sure.
A delusion is a belief that someone holds strongly despite
evidence against it. For example, a delusion of persecution is a
belief that enemies are persecuting you. A delusion of grandeur
is a belief that you are unusually important, perhaps a special
messenger from God. A delusion of reference is a tendency to
take all sorts of messages personally.
Many people with schizophrenia show various problems with
communication, including illogical, incoherent, distracted, or
tangential speech, as if they start speaking but quickly forget
what they are trying to say. Most but not all people with
schizophrenia show intellectual impairments of various types,
especially with attention and working memory.
Another characteristic of schizophrenic thought is difficulty
using abstract concepts, such as interpreting proverbs literally
instead of seeing the intended meaning.
28
Prevalence
Schizophrenia is:
Most frequently diagnosed in young adults in their 20s
More common in men than women
More severe in men
More common among people who grew up in big cities than

among people who grew up in rural areas or small towns
Causes
Much evidence indicates that it is possible to inherit a
predisposition toward schizophrenia.
Neurodevelopmental hypothesis – idea that schizophrenia
originates with nervous system impairments that develop before
birth or in early childhood because of either genetics or early
environment, especially prenatal environment
Worldwide, about one to four people per thousand develop
schizophrenia at some point in life.
Schizophrenia is most frequently diagnosed in young adults in
their 20s, occasionally in teenagers. It is more common in men
than women, by a ratio of about 7 to 5, and on average more
severe in men. Schizophrenia is more common among people
who grew up in big cities than among people who grew up in
rural areas or small towns.
Much evidence indicates that it is possible to inherit a
predisposition toward schizophrenia. Research shows the
relatives of someone with schizophrenia have an increased
probability of developing schizophrenia. A current hypothesis is
that schizophrenia can result from changes in any of a large
number of genes.
Many researchers believe that schizophrenia originates with
abnormal brain development before or around the time of birth
because of either genetics or prenatal environment. Early
abnormal development leaves a person vulnerable to further
deterioration in adulthood.
29

Brain Abnormalities
Many people with schizophrenia show indications of mild brain
abnormalities.
Therapies
Antipsychotic drug – a drug that can relieve schizophrenia
Typical antipsychotic drugs block dopamine synapses in the
brain.
Antipsychotic drugs produce unwelcome side effects.
Tardive dyskinesia – a condition characterized by tremors and
involuntary movements
Atypical antipsychotic drugs – drugs that relieve schizophrenia
without causing tardive dyskinesia
Brain scans indicate that people with schizophrenia have, on
average, decreased gray matter in several brain areas and
slightly enlarged cerebral ventricles, the fluid-filled cavities of
the brain. Most people with schizophrenia also have smaller
than average neurons and fewer than average synapses,
especially in the prefrontal cortex. However, these results must
be interpreted cautiously. Many people with schizophrenia
abuse alcohol or other drugs that might impair brain
functioning, shrink dendrites, and so forth.
Drugs that alleviate schizophrenia block dopamine synapses.
However, antipsychotic drugs produce unpleasant side effects,
including tardive dyskinesia. Atypical (or second-generation)
antipsychotic drugs relieve schizophrenia with less risk of
tardive dyskinesia. However, the atypical antipsychotic drugs
have side effects of their own.
30
Autistic Spectrum Disorder

Autism spectrum disorder – a lifelong condition characterized
by impaired social contact
The main symptoms are:
Impaired social relationships (little eye contact; little social
contact)
Impaired communication (repetitive speech; no sustained
conversations)
Stereotyped behaviors (repetitive movements such as flapping
fingers)
Other symptoms include:
Fluctuations of temperature regulation
Insensitivity to pain
Decreased tendency to become dizzy after spinning with the
lights on
A tendency to focus attention narrowly on one item to the
exclusion of everything else
The causes apparently relate to genetics and prenatal
environment.
Researchers have found many brain abnormalities related to
autism but none that occur consistently.
Autism, a condition that begins in early childhood, is
characterized by impaired social contact, impaired language,
and stereotyped movements.
In addition to the primary symptoms, most individuals with
autism show other symptoms, including fluctuations of
temperature regulation, insensitivity to pain, and decreased
tendency to become dizzy after spinning with the lights on.
Another characteristic is a tendency to focus attention narrowly
on one item to the exclusion of everything else. Many people
with autism perform below average on some intellectual tasks
and above average, sometimes way above average, on other
tasks.

Twin studies point to a strong genetic basis. One study found 92
percent concordance for autism or related problems in
monozygotic twins. That is, if one twin had autism or related
problems, the probability was 92 percent that the other did also.
For dizygotic twins, the concordance was only 10 percent. To
explain this huge discrepancy between monozygotic and
dizygotic twins, one possibility is that autism depends on a
combination of two or more genes. If autism requires two or
three genes, dizygotic twins would have a low probability of
getting the same combination.
Several other possible causes relate to prenatal environment.
About 12 percent of mothers of autistic children have certain
antibodies that attack the proteins of a developing brain. Also,
pregnant women are advised to take folic acid (vitamin B9),
which is important for the developing nervous system. Women
who get enough folic acid from pills or fresh fruit and
vegetables have about half the usual probability of a child with
autism.
Researchers have found many brain abnormalities related to
autism but none that occur consistently. One of the most
surprising is that about one-fifth of people with autism have
large heads and brains—larger than 97 percent of everyone else.
Evidently they have more neurons but abnormal connections
among them. Other abnormalities include decreased number of
neurons in the cerebellum and alterations of neuron structure in
the cerebral cortex.
31
module 15.5
Treatment of Mental Illness
Distinguish among forms of psychotherapy.
Describe how researchers evaluate the effectiveness of

psychotherapy.
Describe possible ways of providing psychotherapeutic help
inexpensively to more people.
List possible methods to prevent psychological disorders.
Discuss the insanity defense and other societal issues related to
mental illness.
32
Table 15.4 Changes in Psychotherapy
Between the 1950s and the 21st CenturyAspect of
Therapy1950sEarly 21st CenturyPaymentBy the patient or
familyBy health insuranceTypes of
therapistPsychiatristsPsychiatrists, clinical psychologists,
othersTypes of treatmentMostly FreudianMany types; emphasis
on evidence-based treatmentsDuration of treatmentUsually long,
often yearsA few sessions if effective; more if
necessaryDiagnosesUsually vague, such as “neurosis” or
“psychosis.” Often, no diagnosis.Many diagnoses. Each
carefully defined.Treatment decisionsBy the therapist and
patientBy the insurer, unless the patient pays for more
Psychotherapy is a treatment of psychological disorders by
methods that include a personal relationship between a trained
therapist and a client. Treatment of mental illness has changed
greatly since the mid-1900s. Table 15.4 summarizes these
changes.
In the mid-1900s, people seeking psychotherapy paid for it
themselves. Today, most people rely on insurance. In the 1950s,

psychiatrists conducted almost all psychotherapy. Today,
clinical psychologists and other specialists also provide
treatment. Today’s therapists use a variety of empirically
supported treatments, with less reliance on Freudian methods.
Therapists try to achieve good results in just a few sessions,
when possible, instead of proceeding for months or years.
Today’s therapists provide diagnoses for more disorders and
define their diagnoses more carefully.
33
Types of Psychotherapy (slide 1 of 3)
Psychodynamic Therapies
Psychodynamic therapies – methods that attempt to understand
conflicting impulses, including some that the individual does
not consciously recognize
Psychoanalysis – method that tries to bring unconscious
thoughts and emotions to consciousness
Techniques used in psychoanalysis:
Free association – procedure in which a client says everything
that comes to mind
Dream analysis – method that seeks to understood symbolism in
reported dreams
Transference – situation in which clients transfer onto the
therapist the behaviors and feelings they originally established
toward their father, mother, or other important person
Psychodynamic therapies attempt to understand conflicting
impulses, including some that the individual does not
consciously recognize. Psychoanalysts try to uncover the
unconscious reasons behind self-defeating behaviors. To bring
the unconscious to consciousness, they rely on free association,
dream analysis, and transference.
34

Behavior Therapy
Behavior therapy – treatment that begins with a clear, well-
defined goal, such as eliminating test anxiety, and then attempts
to achieve it through learning
Cognitive Therapies
Cognitive therapy – procedure that seeks to improve
psychological well-being by changing people’s interpretation of
events
Cognitive-behavior therapy – treatment in which therapists set
explicit behavioral goals, but also try to change people’s
interpretation of situations
Behavior therapists assume that abnormal behavior is learned
and can be unlearned. They identify the behavior that needs to
be changed, such as a fear or bad habit, and then set about
changing it through reinforcement and other principles of
learning. Unlike psychoanalysts, they are more interested in
changing behaviors than in understanding their hidden
meanings.
Behavior therapists set specific goals for changing a client’s
behavior and use learning techniques to help clients achieve
those goals. Setting a clear goal enables a therapist to judge
whether the therapy is succeeding. If the client shows no
improvement, the therapist changes the procedure.
Cognitive therapists identify distressing thoughts (such as
“people don’t like me” or “my enemies are out to get me”) and
try to get clients to replace defeatist thinking with more
favorable views of themselves and the world.
Many therapists combine features of behavior therapy and

cognitive therapy, attempting to change people’s behaviors by
altering how they interpret the situation.
35
Humanistic Therapy
Humanistic therapists assume that people can solve their own
problems.
Person-centered therapy (nondirective or client-centered
therapy) – procedure in which a therapist listens to the client
with total acceptance and unconditional positive regard
Family Systems Therapy
Family systems therapy – treatment based on the assumption
that most people’s problems develop in a family setting and that
the best way to deal with them is to improve family
relationships and communication
Group Therapies
Group therapy – treatment administered to several people at
once
Humanistic psychologists believe that people can decide
deliberately what kind of person to be. According to humanistic
therapists, once people are freed from a feeling of rejection or
failure, they can solve their own problems.
In Carl Rogers’s version of humanistic therapy, person-centered
therapy, also known as nondirective or client-centered therapy,
the therapist listens to the client with total acceptance and
unconditional positive regard. Most of the time, the therapist
paraphrases and clarifies what the client has said, conveying the
message, “I’m trying to understand the experience from your
point of view.” The therapist strives to be genuine, empathic,

and caring, seldom if ever offering interpretation or advice.
In many cases, an individual’s problem is part of an overall
disorder of family communications and expectations. What
distinguishes family therapists is that they prefer to talk with
two or more members of a family together. Solving most
problems requires changing the family dynamics as well as any
individual’s behavior.
Psychotherapy is sometimes provided to people in groups, often
composed of individuals with similar problems. Self-help
groups provide sessions similar to group therapy but without a
therapist. An example of a self-help group is Alcoholics
Anonymous (AA).
36
How Effective is Psychotherapy?/
Comparing Theories
The average person in therapy improves more than at least 80
percent of the equally troubled people not in therapy.
In general, all mainstream therapies appear about equally
effective, although cognitive or cognitive-behavioral therapy is
somewhat better for reducing anxiety or other primary
symptoms.
To evaluate psychotherapy, we cannot simply compare people
who did or did not choose to enter therapy. Those who sought
help might differ from the others in the severity of their
problems or their motivation for improvement. In the best
studies, people who contact a clinic are randomly assigned to
receive therapy at once or wait for therapy later. A few months
later, the investigators evaluate people’s improvement, often by
their answers to a standardized questionnaire.

Most experiments have included only a moderate number of
people. To draw a conclusion, researchers use a method called
meta-analysis, taking the results of many experiments,
weighting each one in proportion to the number of participants,
and determining the overall average effect. According to a
meta-analysis that pooled the results of 475 experiments, the
average person in therapy showed greater improvement than 80
percent of similar people who did not receive therapy.
For a variety of disorders relating to anxiety or depression, all
the mainstream types of therapy appeared nearly equal in
effectiveness. Later research qualified this statement somewhat:
For several types of disorder, cognitive therapy or cognitive -
behavioral therapy produces a slightly greater reduction of the
target symptoms (such as anxiety), but all the common types of
treatment are roughly equal for less specific goals, such as
overall quality of life.
37
Table 15.5 Similarities and Differences
among Four Types of
PsychotherapyProcedurePsychoanalysisBehavior
TherapyCognitive TherapyPerson-Centered TherapyTherapeutic
pect
Table 15.5 highlights similarities and differences among four
types of therapy.
Nearly all forms of psychotherapy include a close relationship

between client and therapist, an effort to discuss personal
difficulties openly, an expectation of improvement, and a
commitment to make changes in one’s life.
38
The Future of Psychotherapy and Prospects for Prevention
Community psychologists – those who try to help people change
their environment, both to prevent disorders and to promote a
positive sense of mental well-being
Prevention – avoiding a disorder from the start
We need careful research to identify effective methods of
prevention and treatment.
Effective prevention programs:
Give participants active practice at specific behaviors
Build up step by step from simpler skills to more complex ones
Work with people at appropriate times in their lives
Examples of effective prevention programs:
Educate pregnant women about prenatal care.
Outlaw smoking in public places and educate people about the
risks of smoking.
Help people get jobs.
Psychologists, especially community psychologists, seek to help
people change their environment to promote mental health.
Prevention is avoiding a disorder from the start. Prevention
takes several forms. A universal program targets everyone, such
as an antismoking campaign, or abolition of lead-based paints
and leaded gasoline. A selective program includes only people
at risk, such as people with a family history of some disorder.
An indicated program identifies people in the early stages of a
disorder and tries to stop it.
Effective prevention programs need careful testing. Many

interventions that sound reasonable don’t work. For example,
prolonged discussions of a stressful experience shortly after the
event are more likely to cause than prevent post-traumatic stress
disorder. “Scared straight” interventions tend to increase, not
decrease, criminal behavior.
The best programs give participants active practice at specific
behaviors, such as resisting peer pressure to risky behaviors.
They build up step by step from simpler skills to more complex
ones. And they work with people at appropriate times in their
lives. For example, AIDS prevention or pregnancy prevention
should start at an age when students might begin to be sexually
active, not many years earlier or many years later.
Examples of effective prevention programs include the
following:
Ban toxins. The sale of lead-based paint has been banned
because children who eat flakes of it sustain brain damage.
Educate pregnant women about prenatal care. The use of alcohol
or other drugs during pregnancy damages the brain of a fetus,
and bacterial and viral infections during pregnancy can impair
fetal brain development.
Outlaw smoking in public places and educate people about the
risks of smoking. Improvements in physical health improve
psychological well-being, too.
Help people get jobs. People who lose their jobs lose self-
esteem and increase their risk of depression and substance
abuse. Summer jobs for low-income teenagers decrease their
probability of violent crime, not only during the summer but
also long after.
Neighborhood improvement. Low-income people who move
from a crime-ridden neighborhood to a less distressed
neighborhood experience long-term benefits in mental health.
Prevent bullying in school. Children who are frequently bullied
have an increased risk of anxiety, depression, and other distress
throughout life.

39
Social Issues Related to Mental Illness
Deinstitutionalization – the removal of patients from mental
hospitals
Deinstitutionalization was and is a good idea in principle but
only if implemented well, and too often it has not been, as many
patients released from mental hospitals do not receive adequate
alternative care.
The Duty to Protect
Tarasoff case – court ruling that a therapist who has reason to
believe that a client is dangerous to someone must warn the
endangered person or take other steps to prevent harm
The Insanity Defense
Some defendants accused of a crime are acquitted for reasons of
insanity, which is a legal rather than a medical or psychological
concept.
M’Naghten rule – statement that someone is legally insane if he
or she was so mentally disordered at the time of an act as not to
understand what he or she was doing
Until the 1950s, huge numbers of troubled people were confined
in understaffed, overcrowded state mental hospitals supported
by the government. In the 1950s, hospitals moved toward
deinstitutionalization, the removal of patients from mental
hospitals, to give them the least restrictive care possible. The
hope was that patients would go home, free to live as normal a
life as possible, while receiving outpatient care at community
mental health centers, which are usually cheaper and more
effective than large mental hospitals. However, implementing
good alternative care isn’t easy, and the effectiveness has been
undependable.

The courts have ruled that a therapist who is convinced that a
client is dangerous should warn the endangered person.
Insanity is a legal term, not a psychological or medical term.
The most famous definition of insanity is the M’Naghten rule.
To be regarded as insane under the M’Naghten rule, people
must be so disordered that they do not understand what they are
doing. Anyone who tries to prevent the police from detecting a
murder or other crime presumably did understand what he or she
was doing.
In the United States, fewer than 1 percent of accused felons
plead insanity, and of those, fewer than 25 percent are found not
guilty. So, no more than 0.25 percent of all defendants are
found not guilty by reason of insanity.
40
What are the Steps in Risk Assessment?
There are four major steps in risk assessment, which is the
determination of the relationship between predicted exposure
and adverse effects. Indeed, a key to the effective risk
management of chemicals contained in a product is the accurate
assessment of the risks associated with the product's particular
applications as well as with the other stages of the product life -
cycle.
The four steps are:
1. hazard identification
2. dose-response evaluation
3. exposure assessment
4. risk characterisation
These steps constitute a general approach to risk assessment

that has been endorsed by a number of national governments
and international organizations such as the International
Programme on Chemical Safety (IPCS), the Organisation for
Economic Cooperation and Development (OECD), the US
Environmental Protection Agency (US EPA) and the European
Union, among others.
Step 1 Hazard Identification
Hazard identification is defined as the identification of the
adverse effects which a chemical has an inherent capacity or
potential to cause. Examples of physical hazards include:
combustion, explosivity, flammability, corrosivity. Examples of
health hazards are either acute ( e.g. skin and eye irritation,
lethal effects, asphyxiation) or chronic (e.g. carcinogenicity,
sensitization, effect on reproductive system, effects on nervous
system, effect on organs). Examples of ecological hazards
include mortality (acute) or reduced growth and reproduction
(chronic) to representative species.
Hazard identification is only the first step in risk assessment
and is not an appropriate basis upon which to make a risk
management decision. However, hazard identification is a
critical step often carried out before chemicals and products are
introduced on the market. For human health and the
environment, results of toxicity testing as well as epidemiology
data are used to determine hazard.
Toxicity is the inherent potential or capacity of a chemical
(generally established from a dose-response relationship) to
cause adverse effects in a living organism that seriously
damages its structure or function or results in death. Toxicity
testing (for humans: toxicity;for the environment: ecotoxicity)
is usually carried out through controlled studies on living
organisms, isolated tissues, cells or cellular components.

Toxicity is generally influenced by the unique physico-chemical
properties of the chemical. Examples of toxicity tests that are
pertinent to human health hazards relate to skin and eye
irritation, sensitization, carcinogenicity, reproduction toxicity.
Examples of ecotoxicity tests that are pertinent to ecological
hazards relate to acute and chronic toxicity to fish and algæ.
The term "toxic" is generally used in a regulatory context to
categorize chemicals based on certain criteria and test results.
Consequently, a chemical that may have a low level of toxicity
(e.g. NaCl: table salt) may not be classified as toxic for
regulatory purposes. In this context, all chemicals have a level
of toxicity (i.e. an inherent ability to cause some adverse effect
under certain controlled conditions) but they are not necessarily
classified as toxic.
Epidemiology is the study of the distribution and likely
determinants of diseases and injuries in human populations. The
incidence of disease is compared between people exposed and
not exposed to the agent under study. Because epidemiology, as
opposed to toxicology, evaluates human rather than animal and
cellular data, it has the potential to be particularly informative
for human hazard identification.
Step 2 Dose-response Evaluation
Dose-response evaluation is the determination of the
relationship between the magnitude of an administered, applied
or internal dose and a specific biological response. The dose is
the total amount of a substance administered to, taken or
absorbed by an organism under standardised laboratory
conditions used for toxicology testing. The response can be
expressed as the measured or observed incidence, the percent
response in groups of subjects (or population), or the
probability of occurrence of a response in a population.

"All substances are poisons; there is none which is not a poison.
The right dose differentiates a poison from a remedy"
Paracelsus, 1493-1541
Step 3 Exposure Assessment
Exposure Assessment is the process of measuring or estimating
concentrations (or intensity), duration and frequency of
exposures to a chemical present in the environment (either
workplace or "outside environment"). Common routes of
exposure are ingestion, injection (less likely), skin absorption
and inhalation. Generally, estimates of exposure are obtained by
determining the emissions, pathways and rates of movement of a
chemical in the workplace or the general environment. There are
a number of methods/ techniques available to estimate or
measure level of exposure. Ecological Risk Assessment
represents an extra challenge in the number of potential
receptors/ species that may need to be considered when
assessing risk.
Step 4 Risk characterization
Risk is the probability that an adverse outcome will occur in a
person, a group of persons or an ecological system that is
exposed to a particular dose or concentration of a chemical. It is
expressed as a probability in values ranging from zero (certainty
that an effect will not occur) to one (100% certainty that an
effect will occur).
Risk characterization is the final stage of risk assessment. It
summarizes the information from hazard identification, dose-
response evaluation and exposure assessment into an overall
conclusion on risk. The result of a risk characterization is a

qualitative and/or quantitative description under specific
exposure conditions. Risk characterization is highly context-
specific and cannot be automatically applied from one context
or location to another. This is because risk should be
determined for a chemical in a product in particular applications
and through other stages of the product life-cycle. Risk
characterization should allow for the identification of the
strengths and weaknesses of the tests used, the uncertainties in
the data base and the assumptions made within the methodology
used to reach the overall conclusions.
Complete characterization of risk is very important to good risk
management and risk communication. Full characterization can
help distinguish between exposures that are likely to be
associated with significant or socially unacceptable risks and
those that are not.
Source:
http://www.eurometaux.org/MetalsToday/MetalsFAQs/Riskasses
sment.aspx
ECOTOXICOLOGY
A ubiquitous tire rubber–derived chemical induces
acute mortality in coho salmon
Zhenyu Tian1,2, Haoqi Zhao3, Katherine T. Peter1,2, Melissa
Gonzalez1,2, Jill Wetzel4, Christopher Wu1,2,
Ximin Hu3, Jasmine Prat4, Emma Mudrock4, Rachel
Hettinger1,2, Allan E. Cortina1,2,
Rajshree Ghosh Biswas5, Flávio Vinicius Crizóstomo Kock5,
Ronald Soong5, Amy Jenne5, Bowen Du6,
Fan Hou3, Huan He3, Rachel Lundeen1,2, Alicia Gilbreath7,

Rebecca Sutton7, Nathaniel L. Scholz8,
Jay W. Davis9, Michael C. Dodd3, Andre Simpson5, Jenifer K.
McIntyre4, Edward P. Kolodziej1,2,3*
In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch),
stormwater exposure annually
causes unexplained acute mortality when adult salmon migrate
to urban creeks to reproduce. By
investigating this phenomenon, we identified a highly toxic
quinone transformation product of
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a
globally ubiquitous tire rubber
antioxidant. Retrospective analysis of representative roadway
runoff and stormwater-affected creeks
of the U.S. West Coast indicated widespread occurrence of
6PPD-quinone (<0.3 to 19 micrograms
per liter) at toxic concentrations (median lethal concentration of
0.8 ± 0.16 micrograms per liter).
These results reveal unanticipated risks of 6PPD antioxidants to
an aquatic species and imply
toxicological relevance for dissipated tire rubber residues.
H
umans discharge tens of thousands of
chemicals and related transformation
products to water (1), most of which re-
main unidentified and lack rigorous
toxicity information (2). Efforts to iden-
tify and mitigate high-risk chemical toxicants
are typically reactionary, occur long after their
use becomes habitual (3), and are frequently
stymied by mixture complexity. Societal man-
agement of inadvertent, yet widespread, chem-
ical pollution is therefore costly, challenging,
and often ineffective.

The pervasive biological degradation of con-
taminated waters near urban areas (“urban
stream syndrome”) (4) is exemplified by an
acute mortality phenomenon that has affected
Pacific Northwest coho salmon (Oncorhynchus
kisutch) for decades (5–9). “Urban runoff mor-
tality syndrome” (URMS) occurs annually
among adult coho salmon returning to spawn
in freshwaters where concurrent stormwater
exposure causes rapid mortality. In the most
urbanized watersheds with extensive imper-
vious surfaces, 40 to 90% of returning salmon
may die before spawning (9). This mortality
threatens salmonid species conservation across
~40% of the Puget Sound land area despite
costly societal investments in physical habitat
restoration that may have inadvertently created
ecological traps through episodic toxic water
pollution (9). Although URMS has been linked
to degraded water quality, urbanization, and
high traffic intensity (9), one or more causal
toxicants have remained unidentified. Spurred
by these compelling observations and mindful
of the many other insidious sublethal storm-
water impacts, we have worked to characterize
URMS water quality (10, 11).
Previously, we reported that URMS-associated
waters had similar chemical compositions rel-
ative to roadway runoff and tire tread wear
particle (TWP) leachates, providing an open-
ing clue in our toxicant search (10). In this
work, we applied hybrid toxicity identifica-
tion evaluation and effect-directed analysis to

screen TWP leachate for its potential to induce
mortality (a phenotypic anchor) in juvenile
coho salmon as an experimental proxy for
adult coho (6). Using structural identifica-
tion by means of ultrahigh-performance liquid
chromatography–high-resolution tandem mass
spectrometry (UPLC-HRMS/MS) and nuclear
magnetic resonance (NMR), we discovered
that an antioxidant-derived chemical was the
primary causal toxicant. Retrospective anal-
ysis of runoff and receiving waters indicated
that detected environmental concentrations
of this toxicant often exceeded acute mortality
thresholds for coho during URMS events in
the field and across the U.S. West Coast.
Aqueous TWP leachate stock (1000 mg/liter)
was generated from an equal-weight mix of
tread particles (0.2 ± 0.3 mm2 average surface
area) (fig. S1) from nine used and new tires
(table S1). TWP leachate (250 mg/liter posi-
tive controls) was acutely and rapidly (~2 to
6 hours) lethal to juvenile coho (24 hours ex-
posures, 98.5% mortality, n = 135 fish from
27 exposures) (data file S1), even after heating
(80°C, 72 hours; 100% mortality, n = 10 fish
from two exposures), indicating stability dur-
ing handling. Behavioral symptomology (circl-
ing, surface gaping, and equilibrium loss) (fig.
S2 and movie S1) of TWP leachate exposures
mirrored laboratory and field observations of
symptomatic coho (5, 6). No mortality occurred
in negative controls, including solvent- and
process-matched method blanks subjected
to identical separations (0 of 80 fish, 16 expo-

sures) or exposure water blanks (0 of 45 fish,
nine exposures).
Mixture complexity [measured here as num-
ber of UPLC-HRMS electrospray ionization
(ESI+) chemical features] was a substantial
barrier to causal toxicant identification be-
cause 250 mg/liter TWP leachate typically
contained more than 2000 ESI+ detections.
Our fractionation studies, optimized over
2-plus years through iterative exploration of
toxicant chemical properties, focused on re-
ducing these detection numbers to attain a
simple, yet toxic, fraction amenable to indi-
vidual compound identifications. Throughout
this fractionation procedure, observed toxicity
remained confined to one narrow fraction,
which is consistent with a single compound
or a small, structurally related family of causal
toxicants. In initial studies, TWP leachate toxi-
city was unaffected by silica sand filtration,
cation and anion exchange, and ethylenedia-
minetetraacetic acid (EDTA) (114 mM) addi-
tion (12), indicating that toxicant(s) were not
particle-associated, strongly ionic, or metals,
respectively, and validating prior studies that
eliminated candidate pollutants (13, 14) as pri-
mary causal toxicants.
Mixture complexity was reduced by using
cation exchange, two polarity-based separa-
tions (XAD-2 resin and silica gel), and reverse-
phase high-performance liquid chromatography
(HPLC) on a semipreparative C18 column
(250 by 4.2 mm ID, 5 mm particle size). After
C18-HPLC generated 10 fractions, only C18-F6

(10 to 11 min) was toxic; it contained ~225 ESI+
and ~70 ESI– features (Fig. 1). Having removed
~90% of features, we began to prioritize and
identify candidate toxicants by abundance
(peak area), followed by fish exposures with
commercial standards at fivefold higher con-
centrations (mixtures at 1 to 25 mg/liter) than
those estimated in C18-F6. We identified 11 plas-
ticizers, antioxidants, emulsifiers, and various
transformation products, including some well-
known environmental contaminants [such as
tris(2-butoxyethyl) phosphate] and some that
are rarely reported [such as di(propylene gly-
col) dibenzoate and 2-(1-phenylethyl)phenol]
(table S2). We also detected several bioac-
tive, structurally related phenolic antioxidants
and their transformation products (2,6-di-t-
RESEARCH
Tian et al., Science 371, 185–189 (2021) 8 January 2021 1 of 5
1Center for Urban Waters, Tacoma, WA 98421, USA.
2Interdisciplinary Arts and Sciences, University of
Washington Tacoma, Tacoma, WA 98421, USA. 3Department
of Civil and Environmental Engineering, University of
Washington, Seattle, WA 98195, USA. 4School of the
Environment, Washington State University, Puyallup, WA
98371, USA. 5Department of Chemistry, University of
Toronto, Scarborough Campus, 1265 Military Trail, Toronto,
ON M1C 1A4, Canada. 6Southern California Coastal Water
Research Project, Costa Mesa, CA 92626, USA. 7San
Francisco Estuary Institute, 4911 Central Avenue, Richmond,
CA 94804, USA. 8Environmental and Fisheries Sciences
Division, Northwest Fisheries Science Center, National Marine
Fisheries Service, National Oceanic and Atmospheric

Administration, Seattle, WA 98112, USA. 9U.S. Fish and
Wildlife Service, Washington Fish and Wildlife Office, Lacey,
WA 98503, USA.
*Corresponding author. Email: [email protected]
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http://science.sciencemag.org/
butyl-4-hydroxy-4-methyl-2,5-cyclohexadie-
none, 3,5-di-t-butyl-4-hydroxybenzaldehyde,
and 7,9-di-tert-butyl-1-oxaspiro[4,5]deca-6,9-
diene-2,8-dione) (15). However, over many
rounds of identification and subsequent ex-
posure to juvenile coho, none of these identi-
fied chemical exposures reproduced URMS
symptoms or induced mortality. Because these
identifications used exhaustive environmental
scientific literature searches (10, 16, 17), we
suspected a previously unreported toxicant.
To sharpen our search, we used multidi-

mensional semipreparative HPLC using two
additional structurally distinct column phases
[pentafluorophenyl (PFP) and phenyl]. Paral-
lel fractionations (same column dimensions,
mobile phase, and gradient as for C18-HPLC)
(18) of the toxic silica gel fraction generated
toxic fractions of PFP-F6 (10 to 11 min; ~204
ESI+, 60 ESI– features) and phenyl-F4 (8 to
9 min; ~237 ESI+, 75 ESI– features); all other
fractions were nontoxic. Across these sepa-
rations (C18, PFP, phenyl), only four ESI+ and
three ESI– HRMS features co-occurred in all
three toxic fractions (fig. S3). Of these, one
unknown compound [mass/charge ratio (m/z)
299.1752, C18H22N2O2, RT 11.0 min on ana-
lytical UPLC-HRMS] dominated the detected
peak area (10-fold higher intensity in both
ESI+ and ESI–). To further resolve candidate
toxicants for synthetic efforts, we converted
the three-dimensional chromatography work-
flow from parallel to serial through sequen-
tial C18, PFP, and phenyl columns (C18-F6 to
PFP-F6 to phenyl-F4; with solvent removal
by means of centrifugal evaporation and tox-
icity confirmation between separations). The
purified final fraction was chemically simple
(four ESI+, three ESI– detections), highly lethal
(100% mortality in 4 hours; n = 15 coho, three
exposures), and was again dominated by
C18H22N2O2. Drying this fraction yielded a
pink-magenta precipitate (Fig. 1).
Published characterizations of crumb rub-
ber (16) and receiving waters (10, 17) did not
mention C18H22N2O2. UPLC-HRMS/MS spectra
indicated C4H10 and C6H12 alkyl losses (M-58

and M-84 fragments) (Fig. 2B), but MS3 and
MS4 fragmentation yielded no additional
structural insights (fig. S4). Additionally, in
silico fragmentation (MetFrag, CSI:FingerID)
of C18H22N2O2 compounds in PubChem and
ChemSpider (15,624 and 17,105 structures, re-
spectively) failed to match observed fragments.
Thus, to the best of our knowledge, C18H22N2O2
was not described in environmental literature
or databases and posed a “true unknown” iden-
tification problem (19). We then assumed a
transformation product; industrial manu-
facturing (such as high heat or pressure, or
catalysis) and diverse reactions in environ-
mental systems generate many undocumented
transformation products, most of which lack
commercial standards.
Fig. 1. Tire rubber leachate fractionation scheme. As a metric of
mixture complexity and separation
efficiency, the numbers above gray bars represent distinct
chemical features detected in solid-phase
extracted fish exposure water (1 liter) and subsequent fractions
by means of UPLC-HRMS. Blue indicates
nonlethal fractions; red indicates lethal fractions. All
fractionation steps and exposures were replicated
at least twice; positive and negative controls were included
throughout fractionations. (Inset) Purified product
(~700 mg from 30 liter of TWP leachate) in the final lethal
fraction. TWP, tire tread wear particles; CEX,
cation exchange; EA, ethyl acetate; EtOH, ethanol; H2O, water;
Hex, hexane; DCM, dichloromethane; RT,
retention time.

Fig. 2. 6PPD-quinone identification and a proposed formation
pathway. (A) Extracted ion chromato-
grams of 6PPD-quinone from UPLC-HRMS (ESI+); red data
indicate the final fraction from TWP leachate,
and black data indicate the purified 6PPD ozonation mixture.
(B) Observed MS/MS fragmentation
(integrated from 10, 20, and 40 eV) of 6PPD-quinone in the
final toxic fraction from TWP leachate
(red spectra) and 6PPD ozonation (black spectra). (C) One
proposed reaction pathway from 6PPD to
6PPD-quinone (alternate proposed formation pathways are
provided in fig. S13). Red highlights indicate
key changes in the diphenylamine structure during ozonation.
RESEARCH | REPORT
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Our breakthrough came by
assuming that abiotic environ-

mental transformations com-
monly modify active functional
groups by preferentially altering
the numbers of hydrogen and
oxygen atoms relative to carbon
and nitrogen. By searching a
recent U.S. Environmental Pro-
tection Agency (EPA) crumb
rubber report (16) for related
formulas (C18H0-xN2-4O0-y), sev-
eral characteristics of the C18H24N2
anti-ozonant “6PPD” [N-(1,3-
dimethylbutyl)-N′-phenyl-p-
phenylenediamine] matched
necessary attributes. First, 6PPD
is globally ubiquitous (0.4 to 2%
by mass) in passenger and com-
mercial vehicle tire formulations
(20), indicating sufficient pro-
duction to explain mortality
observations within large and
geographically distinct receiv-
ing water volumes. 6PPD was
present in TWP leachate but was
completely removed during frac-
tionation through cation ex-
change. 6PPD crystals are purple,
similar to the pink-magenta pre-
cipitate obtained after fractiona-
tion. Most compellingly, neutral
losses in 6PPD gas chromatog-
raphy (GC)–MS spectra matched
the C18H22N2O2 GC-HRMS spec-
tra (fig. S5), and the predicted
logKow of 6PPD (5.6) (Kow, n-
octanol-water partition coeffi-

cient) was close to that for
C18H22N2O2 (5 to 5.5) (11). Last,
literature detailing the indus-
trial chemistry of 6PPD reactions
with ozone [7 days, 500 parts per billion vol-
ume (ppbv)] described a C18H22N2O2 product
(21), leading us to hypothesize that 6PPD was
the likely protoxicant (Fig. 2C).
We tested this hypothesis with gas-phase
ozonation (500 ppbv O3) of industrial grade
6PPD (96% purity) (21). A C18H22N2O2 prod-
uct formed; UPLC-HRMS analysis demon-
strated exact matches of retention time (11.0 min)
and MS/MS spectra between this synthetic
C18H22N2O2 and the TWP leachate fractionation-
derived C18H22N2O2 (Fig. 2, A and B). When
purified, the ozone-synthesized C18H22N2O2
formed a reddish-purple precipitate. One-
dimensional 1H NMR structural analysis con-
firmed identical TWP leachate–derived and
ozone-synthesized C18H22N2O2 structures (figs.
S6 to S7). Two-dimensional NMR spectra and
related simulations revealed isolated tertiary
carbons and carbonyl groups (figs. S8 to S12),
clearly indicating a quinone structure for
C18H22N2O2 rather than the dinitrone struc-
ture reported in the past 40 years of literature
describing 6PPD ozonation products (21).
Therefore, the C18H22N2O2 candidate toxicant
was unequivocally “6PPD-quinone” {2-anilino-
5-[(4-methylpentan-2-yl)amino]cyclohexa-2,5-
diene-1,4-dione}. Consistent with environmental
6PPD ozonation, reported 6PPD ozonation
products C18H22N2O (formula-matched) and

4-nitrosodiphenylamine (C12H10N2O, standard-
confirmed) (21) also were detected in ozo-
nation mixtures and nontoxic TWP leachate
fractions.
Exposures to ozone-synthesized and tire
leachate–derived 6PPD-quinone (~20 mg/liter
nominal concentrations) both induced rapid
(<5 hours, with initial symptoms evident
within 90 min) mortality (n = 15 fish, three
exposures) (fig. S2 and movie S2), which
matched the 2 to 6 hours mortality observed
for positive controls. Behavioral symptomol-
ogy in response to synthetic 6PPD-quinone
exposures matched that from field observa-
tions, roadway runoff, bulk TWP
leachate, and final toxic TWP frac-
tion exposures, confirming the
phenotypic anchor (5–9). Using
synthetic 6PPD-quinone (purity
~98%), we performed controlled
dosing experiments (10 concen-
trations, n = 160 fish in two inde-
pendent exposures). 6PPD-quinone
was highly toxic [median lethal
concentration (LC50) 0.79 ± 0.16 mg/
liter] to juvenile coho salmon (Fig.
3B). Estimates of LC50 through con-
trolled exposures closely matched
estimates derived from bulk road-
way runoff and TWP leachate expo-
sures (LC50 0.82 ± 0.27 mg/liter),
indicating the primary contribution
of 6PPD-quinone to observed mix-
ture toxicity (Fig. 3A). Direct com-

parisons with 6PPD were performed
(LC50 250 ± 60 mg/liter through no-
minal concentrations) (fig. S14), but
confident assessment of 6PPD toxi-
city was precluded by its poor solu-
bility, high instability, and formation
of products during exposure.
To assess environmental rele-
vance, we used UPLC-HRMS to ret-
rospectively quantify 6PPD-quinone
in archived extracts from roadway
runoff and receiving water sam-
pling (fig. S15 and table S4) (10). In
Seattle-region roadway runoff (n =
16 of 16 samples), 0.8 to 19 mg/liter
6PPD-quinone was detected (Fig.
4A). During seven storm events in
three Seattle-region watersheds
highly affected by URMS, 6PPD-
quinone occurred at <0.3 to 3.2 mg/
liter (n = 6 of 7 discrete storm
events; n = 6 of 21 samples when
including samples collected across the full
hydrograph). These samples included three
storms with documented URMS mortality in
adult coho salmon; 6PPD-quinone was not
detected in pre- and poststorm samples, but
concentrations were near or above LC50 values
during storms. We also detected 6PPD-quinone
in Los Angeles region roadway runoff (n = 2 of
2 samples, 4.1 to 6.1 mg/liter) and San Francisco
region creeks affected by urban runoff (n = 4 of
10 samples, 1.0 to 3.5 mg/liter).
These data implicate 6PPD-quinone as the

primary causal toxicant for decades of storm-
water-linked coho salmon acute mortality ob-
servations. Although minor contributions from
other constituents in these complex mixtures
are possible, 6PPD-quinone was both necessary
(consistently present in and absent from toxic
and nontoxic fractions, respectively) and, when
purified or synthesized as a pure chemical ex-
posure, sufficient to produce URMS at envi-
ronmental concentrations. Over the product
Fig. 3. Dose-response curves. (A) Dose-response curve for 24-
hour juvenile
coho exposures to roadway runoff and TWP leachate (n = 365
fish). Error bars
represent three replicates of eight fish (except TWP leachate 2,
n = 5 fish; Seattle
site 1, duplicate of n = 10 fish). 6PPD-quinone concentrations
were from
retrospective quantification. (B) Dose-response curves for 24-
hour juvenile coho
exposures to ozone-synthesized 6PPD-quinone (10
concentrations, two replicates,
n = 160 fish). Curves were fitted to a four-parameter logistic
model. CI,
confidence interval.
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life cycle, antioxidants [such as PPDs, TMQs
(2,2,4-trimethyl-1,2-dihydroquinoline), and
phenolics] are designed to diffuse to tire rub-
ber surfaces, rapidly scavenge ground-level
atmospheric ozone and other reactive oxidant
species, and form protective films to prevent
ozone-mediated oxidation of structurally im-
portant rubber elastomers (21, 22). Accord-
ingly, all 6PPD added to tire rubbers is designed
to react, intentionally forming 6PPD-quinone
and related transformation products that are
subsequently transported through the environ-
ment. This anti-ozonant application of 6PPD
inadvertently, yet drastically, increases road-
way runoff toxicity and environmental risk by
forming the more toxic and mobile 6PPD-
quinone transformation product. On the basis
of the ubiquitous use and substantial mass
fraction (0.4 to 2%) of 6PPD in tire rubbers
and the representative detections across the
U.S. West Coast (table S4), which include many
detections near or above LC50 values, we believe

that 6PPD-quinone may be present broadly in
peri-urban stormwater and roadway run-off at
toxicologically relevant concentrations for sen-
sitive species, such as coho salmon.
Globally, ~3.1 billion tires are produced an-
nually for our more than 1.4 billion vehicles,
resulting in an average 0.81 kg per capita an-
nual emission of tire rubber particles (23).
TWPs are one of the most substantial micro-
plastics sources to freshwaters (24); 2 to 45%
of total tire particle loads enter receiving waters
(25, 26), and freshwater sediment contains up
to 5800 mg/kg TWP (23, 24, 27). Supporting
recent concerns about microplastics (24, 28),
6PPD-quinone provides a compelling mecha-
nistic link between environmental microplas-
tic pollution and associated chemical toxicity
risk. Although numerous uncertainties exist
regarding the occurrence, fate, and transport
of 6PPD-quinone, these data indicate that
aqueous and sediment environmental TWP
residues can be toxicologically relevant and
that existing TWP loading, leaching, and tox-
icity assessments in environmental systems
are clearly incomplete (25). Tire rubber dis-
posal also represents a major global materials
problem and potential potent source of 6PPD-
quinone and other tire-derived transformation
products. In particular, scrap tires repurposed
as crumb rubber in artificial turf fields (17)
suggest both human and ecological expo-
sures to these chemicals. Accordingly, the
human health effects of such exposures merit
evaluation.

Environmental discharge of 6PPD-quinone
is particularly relevant for the many receiving
waters proximate to busy roadways (Fig. 4B).
It is unlikely that coho salmon are uniquely
sensitive, and the toxicology of 6PPD transfor-
mation products in other aquatic species should
be assessed. For example, used tires were more
toxic to rainbow trout (75% lower 96 hours
LC50) relative to new tires (29), an observation
that is consistent with adverse outcomes me-
diated by transformation products. If manage-
ment of 6PPD-quinone discharges is needed to
protect coho salmon or other aquatic orga-
nisms, adaptive regulatory and treatment strat-
egies (17, 30, 31) along with source control and
“green chemistry” substitutions [identifying
demonstrably nontoxic and environmentally
benign replacement antioxidants (22, 32)] can
be considered. More broadly, we recommend
more careful toxicological assessment for trans-
formation products of all high-production-
volume commercial chemicals subject to
pervasive environmental discharge.
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reaction with ground-level ozone to form 6PPD-quinone.
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ACKNOWLEDGMENTS
We thank D. Whittington; S. Edgar (University of Washington
Medicine Mass Spectrometry); M. Bozlee (City of Tacoma);
J. Protasio; A. Rue (Washington State Department of Ecology);

M. Goehring (King County); D. E. Latch (Seattle University); J.
E. Baker;
C. A. James; A. D. Gipe (University of Washington Tacoma);
M. Yu
(Mount Sinai); S. D. Richardson (University of South Carolina);
J. R. Cameron [National Oceanic and Atmospheric
Administration
(NOAA) NWFSC]; K. King (U.S. Fish and Wildlife Service);
Washington
State Department of Transportation; and dedicated citizen
scientists
from the Miller Walker Community Salmon Investigation, Puget
Soundkeeper, and Thornton Creek Alliance. We gratefully thank
the
Puyallup Tribe and NOAA NWFSC for providing juvenile coho
and
Agilent Technologies (T.A. and D.C.) for technical support.
Funding:
This work was supported by NSF grants 1608464 and 1803240,
EPA grant 01J18101 (E.P.K.), DW-014-92437301 (N.L.S.,
J.K.M., and
J.W.D.), Washington State Governors Funds (J.K.M. and
E.P.K.), the
Burges Fellowship (H.Z.), the Regional Monitoring Program for
Water
Quality in San Francisco Bay (A.G. and R.S.), Brazilian
foundation
agency FAPESP (2018/16040-5 and 2019/14770-9) (F.V.C.K.),
NSERC
Alliance (ALLRP 549399) and Discovery (RGPIN-2019-04165)
Programs, the Canada Foundation for Innovation (CFI), the
Ontario
Ministry of Research and Innovation, and the Krembil
Foundation (A.S.).
Disclaimer: Findings and conclusions herein are those of the
authors

and do not necessarily represent the views of the sponsoring
organizations. Author contributions: Z.T., H.Z., K.T.P., J.K.M.,
M.C.D.,
and E.P.K. designed research; Z.T., H.Z., M.G., K.T.P., C.W.,
R.H., and
A.E.C. performed fractionation experiments; Z.T., K.T.P., R.L.,
and M.G.
performed HRMS and data analysis; Z.T., H.Z., M.G., J.W.,
K.T.P.,
C.W., R.H., E.P.K., J.K.M., and A.E.C. conducted fish
exposures; J.P.,
C.W., and J.W. generated TWP particles; J.W., J.P., E.M., and
J.K.M.
maintained the fish facility and enabled exposure studies;
R.G.B.,
F.V.C.K., R.S., A.J., and A.S. elucidated structures by means of
NMR;
K.T.P., C.W., F.H., Z.T., M.G., B.D., A.G., and R.S. provided
water
samples; X.H., Z.T., H.Z., H.H., and M.C.D. performed
ozonation
experiments; N.L.S. and J.W.D. provided perspectives and
context; and
Z.T., H.Z., K.T.P., and E.P.K. wrote the manuscript. Competing
interests: None declared. Data and materials availability: Data
file S1
includes the record of the juvenile coho salmon exposure
experiments.
Number of tanks and coho salmon used, mortality results, and
treatment information are included inthe table. All other data
needed to
evaluate the conclusions in the paper are present in the paper or
the
supplementary materials.

SUPPLEMENTARY MATERIALS
science.sciencemag.org/content/371/6525/185/suppl/DC1
Materials and Methods
Supplementary Text
Figs. S1 to S15
Tables S1 to S5
References (33–47)
Movies S1 and S2
Data File S1
8 July 2020; accepted 5 November 2020
Published online 3 December 2020
10.1126/science.abd6951
RESEARCH | REPORT
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https://science.sciencemag.org/content/371/6525/185/suppl/DC1

derived chemical induces acute mortality in coho salmon−A
ubiquitous tire rubber
Michael C. Dodd, Andre Simpson, Jenifer K. McIntyre and
Edward P. Kolodziej
Jenne, Bowen Du, Fan Hou, Huan He, Rachel Lundeen, Alicia
Gilbreath, Rebecca Sutton, Nathaniel L. Scholz, Jay W. Davis,
Mudrock, Rachel Hettinger, Allan E. Cortina, Rajshree Ghosh
Biswas, Flávio Vinicius Crizóstomo Kock, Ronald Soong, Amy
Zhenyu Tian, Haoqi Zhao, Katherine T. Peter, Melissa
Gonzalez, Jill Wetzel, Christopher Wu, Ximin Hu, Jasmine Prat,
Emma
originally published online December 3, 2020DOI:
10.1126/science.abd6951
(6525), 185-189.371Science
, this issue p. 185Science
show concentrations of 6PPD-quinone high enough to account
for the acute toxicity events.
intended to prevent damage to tire rubber from ozone.
Measurements from road runoff and immediate receiving waters
1 microgram per liter. The compound, called 6PPD-quinone, is
an oxidation product of an additive∼concentrations of
through chromatography steps, eventually isolating a single
molecule that could induce acute toxicity at threshold
followed toxic fractionset al.not been known. Starting from
leachate from new and aged tire tread wear particles, Tian
hasRegular acute mortality events are tied, in particular, to
stormwater runoff, but the identity of the causative toxicant(s)
For coho salmon in the U.S. Pacific Northwest, returning to

spawn in urban and suburban streams can be deadly.
Tire tread particles turn streams toxic
ARTICLE TOOLS
http://science.sciencemag.org/content/371/6525/185
MATERIALS
SUPPLEMENTARY
http://science.sciencemag.org/content/suppl/2020/12/02/science.
abd6951.DC1
CONTENT
RELATED
http://science.sciencemag.org/content/sci/370/6521/1145.full
REFERENCES
http://science.sciencemag.org/content/371/6525/185#BIBL
This article cites 43 articles, 1 of which you can access for free
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is a registered trademark of AAAS.ScienceScience, 1200 New
York Avenue NW, Washington, DC 20005. The title
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Copyright © 2021, American Association for the Advancement
of Science
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http://science.sciencemag.org/content/371/6525/185
http://science.sciencemag.org/content/suppl/2020/12/02/science.
abd6951.DC1
http://science.sciencemag.org/content/sci/370/6521/1145.full
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