How addiction hijacks the brain INSIDE

VOL UME 28 ? N UMBER 1 july 2011

How addiction hijacks the brain

Desire initiates the process, but learning sustains it.

T he word "addiction" is derived from a Latin term for "enslaved by" or "bound to." Anyone who has strug

ever, have shown that certain pleasurable activities, such as gambling, shopping, and sex, can also co-opt the brain. Although the

gled to overcome an addiction--or has tried Diagnostic and Statistical Manual of Men-

to help someone else to do so--understands tal Disorders, Fourth Edition (DSM-IV) de

why.

scribes multiple addictions, each tied to a

Addiction exerts a long and powerful in specific substance or activity, consensus

fluence on the brain that manifests in three is emerging that these may represent mul

distinct ways: craving for the object of ad tiple expressions of a common underlying

diction, loss of control over its use, and brain process.

continuing involvement with it despite ad

verse consequences. While overcoming ad From liking to wanting

diction is possible, the process is often long, Nobody starts out intending to develop an

slow, and complicated. It took years for re addiction, but many people get caught in its

searchers and policymakers to arrive at this snare. According to the latest government

understanding.

statistics, nearly 23 million Americans--

In the 1930s, when researchers first began almost one in 10--are addicted to alcohol or

to investigate what caused addictive behav other drugs. More than two-thirds of people

ior, they believed that people who developed with addiction abuse alcohol. The top three

addictions were somehow morally flawed or drugs causing addiction are marijuana, opi

lacking in willpower. Overcoming addiction, oid (narcotic) pain relievers, and cocaine.

they thought, involved punishing miscreants Genetic vulnerability contributes to the

or, alternately, encouraging them to muster risk of developing an addiction. Twin and

the will to break a habit.

adoption studies show that about 40% to

The scientific consensus has changed 60% of susceptibility to addiction is heredi

since then. Today we recognize addic tary. But behavior plays a key role, especially

tion as a chronic disease that changes both when it comes to reinforcing a habit.

brain structure and function. Just as cardio Pleasure principle. The brain registers

vascular disease damages the heart and dia all pleasures in the same way, whether they

betes impairs the pancreas, addiction hijacks originate with a psychoactive drug, a mone

the brain. Recovery from addiction involves tary reward, a sexual encounter, or a satisfy

willpower, certainly, but it is not enough ing meal. In the brain, pleasure has a distinct

to "just say no"--as the 1980s slogan sug signature: the release of the neurotransmit

gested. Instead, people typically use multiple ter dopamine in the nucleus accumbens, a

strategies--including psychotherapy, medica cluster of nerve cells lying underneath the

tion, and self-care--as they try to break the cerebral cortex (see illustration, page 3). Do

grip of an addiction.

pamine release in the nucleus accumbens is

Another shift in thinking about addiction so consistently tied with pleasure that neuro

has occurred as well. For many years, ex scientists refer to the region as the brain's

perts believed that only alcohol and powerful pleasure center.

drugs could cause addiction. Neuroimaging All drugs of abuse, from nicotine to her

technologies and more recent research, how oin, cause a particularly powerful surge

INSIDE

When depression starts in the neck. . . . . . . . . . . . . . . 4 Treating an underactive thyroid gland may improve mood.

Expressive writing for mental health. . . . . . . . . . . . 6 Putting an experience into words may ease stress and trauma.

In brief. . . . . . . . . . . . . . . . 7 Long-term results of deep brain stimulation for depression; More evidence that exercise aids the brain.

Commentary. . . . . . . . . . . 8 FDA panel finds no link between food colorings and hyperactivity in most children.

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Addiction continued

of dopamine in the nucleus accumbens. substance or behavior causes nerve cells

The likelihood that the use of a drug or in the nucleus accumbens and the pre

participation in a rewarding activity will frontal cortex (the area of the brain in

lead to addiction is directly linked to the volved in planning and executing tasks)

speed with which it promotes dopamine to communicate in a way that couples

release, the intensity of that release, and liking something with wanting it, in turn

the reliability of that release. Even taking driving us to go after it. That is, this pro

the same drug through

cess motivates us to

different methods of administration can in fluence how likely it is to lead to addiction. Smoking a drug or in

Resources

National Clearinghouse for Alcohol and Drug Information P.O. Box 2345 Rockville, MD 20847

take action to seek out the source of pleasure.

Tolerance and compulsion. Over time, the brain adapts in a way

jecting it intravenously, 800-729-6686 (toll-free) as opposed to swal

that actually makes the sought-after sub

lowing it as a pill, for example, generally pro duces a faster, stronger dopamine signal and is

National Institute on Alcohol Abuse and Alcoholism 5635 Fishers Lane, MSC 9304 Bethesda, MD 20892 301-443-3860

stance or activity less pleasurable.

In nature, rewards usually come only with

more likely to lead to niaaa.

time and effort. Addic

drug misuse.

National Institute on Drug Abuse tive drugs and behav

Learning process. Scientists once believed that the experience of pleasure alone was enough to prompt peo ple to continue seeking

6001 Executive Blvd., Room 5213 Bethesda, MD 20892 301-443-1124 nida.

Substance Abuse and Mental Health Services Administration 1 Choke Cherry Road

iors provide a shortcut, flooding the brain with dopamine and other neurotransmitters. Our brains do not have an easy way to withstand

an addictive substance or activity. But more recent research sug

Rockville, MD 20857 877-276-4727 (toll-free)

the onslaught. Addictive drugs, for

example, can release

gests that the situation

two to 10 times the

is more complicated. Dopamine not only amount of dopamine that natural re

contributes to the experience of plea wards do, and they do it more quickly

sure, but also plays a role in learning and and more reliably. In a person who be

memory--two key elements in the tran comes addicted, brain receptors become

sition from liking something to becom overwhelmed. The brain responds by

ing addicted to it.

producing less dopamine or eliminat

According to the current theory about ing dopamine receptors--an adapta

addiction, dopamine interacts with an tion similar to turning the volume down

other neurotransmitter, glutamate, to on a loudspeaker when noise becomes

take over the brain's system of reward- too loud.

related learning. This system has an im As a result of these adaptations, do

portant role in sustaining life because it pamine has less impact on the brain's

links activities needed for human sur reward center. People who develop an

vival (such as eating and sex) with plea addiction typically find that, in time, the

sure and reward. The reward circuit in desired substance no longer gives them

the brain includes areas involved with as much pleasure. They have to take more

motivation and memory as well as with of it to obtain the same dopamine "high"

pleasure. Addictive substances and be because their brains have adapted--an

haviors stimulate the same circuit--and effect known as tolerance.

then overload it.

At this point, compulsion takes over.

Repeated exposure to an addictive The pleasure associated with an addic

2 | Harvard Mental Health Letter | July 2011

health.harvard.edu

tive drug or behavior subsides--and yet the memory of the desired effect and the need to recreate it (the wanting) persists. It's as though the normal machinery of motivation is no longer functioning.

The learning process mentioned earlier also comes into play. The hip pocampus and the amygdala store in formation about environmental cues associated with the desired substance, so that it can be located again. These memories help create a conditioned response--intense craving--whenever the person encounters those environ mental cues.

Cravings contribute not only to ad diction but to relapse after a hard-won sobriety. A person addicted to heroin may be in danger of relapse when he sees a hypodermic needle, for exa mple, while another person might start to drink again after seeing a bottle of whiskey. Conditioned learning helps explain why people who develop an addiction risk relapse even after years of abstinence.

The long road to recovery

Because addiction is learned and stored in the brain as memory, recov ery is a slow and hesitant process in which the influence of those memories diminishes.

About 40% to 60% of people with a drug addiction experience at least one relapse after an initial recovery. While this may seem discouraging, the relapse rate is similar to that in other chronic diseases, such as high blood pressure and asthma, where 50% to 70% of peo ple each year experience a recurrence of symptoms significant enough to re quire medical intervention.

Fortunately a number of effective treatments exist for addiction, usually combining self-help strategies, psycho therapy, and rehabilitation. For some types of addictions, medication may also help. (We've covered specific ad dictions in detail in previous articles. See Harvard Mental Health Letter,

The brain's reward center

Cerebral cortex

Nucleus accumbens

Amygdala

Hippocampus

Addictive drugs provide a shortcut to the brain's reward system by flooding the nucleus accumbens with dopamine. The hippocampus lays down memories of this rapid sense of satisfaction, and the amygdala creates a conditioned response to certain stimuli.

March 2009, January 2010, and April 2011.)

The precise plan varies based on the nature of the addiction, but all treat ments are aimed at helping people to unlearn their addictions while adopt ing healthier coping strategies--truly a brain-based recovery program.

Benowitz NL. "Nicotine Addiction," The New England Journal of Medicine (June 17, 2010): Vol. 362, No. 24, pp. 2295?303.

Brady KT, et al., eds. Women and Addiction: A Comprehensive Handbook (The Guilford Press, 2009).

Chandler RK, et al. "Treating Drug Abuse and Addiction in the Criminal Justice System: Improving Public Health and Safety," Journal of the American Medical Association (Jan. 14, 2009): Vol. 301, No. 2, pp. 183?90.

Greenfield SF, et al. "Substance Abuse Treat ment Entry, Retention, and Outcome in Women: A Review of the Literature," Drug and Alcohol Dependence (Jan. 5, 2007): Vol. 86, No. 1, pp. 1?21.

tion (Oct. 4, 2000): Vol. 284, No. 13, pp. 1689?95.

National Institute on Drug Abuse. Drugs, Brains, and Behavior: The Science of Addiction (National Institutes of Health, Aug. 2010).

Polosa R, et al. "Treatment of Nicotine Addic tion: Present Therapeutic Options and Pipeline Developments," Trends in Pharmacological Sciences (Jan. 20, 2011): E-publication.

Potenza MN, et al. "Neuroscience of Behav ioral and Pharmacological Treatments for Addictions," Neuron (Feb. 24, 2011): Vol. 69, No. 4, pp. 695?712.

Shaffer HJ, et al. "Toward a Syndrome Model of Addiction: Multiple Expressions, Common Etiology," Harvard Review of Psychiatry (Nov.? Dec. 2004): Vol. 12, No. 6, pp. 367?74. *

Stead LF, et al. "Nicotine Replacement Therapy for Smoking Cessation," Cochrane Database of Systematic Reviews (Jan. 23, 2008): Doc. No. CD000146.

Substance Abuse and Mental Health Services Administration. National Survey on Drug Use & Health, 2009.

Koob GF, et al. "Neurocircuitry of Addiction," Neuropsychopharmacology (Jan. 2010): Vol. 35, No. 1, pp. 217?38.

McLellan AT, et al. "Drug Dependence, A Chronic Medical Illness: Implications for Treatment, Insurance, and Outcomes Evalua tion," Journal of the American Medical Associa-

* Harvard Mental Health Letter subscribers can obtain a special discounted subscription to the Harvard Review of Psychiatry by visiting the Web site or by calling 212-520-2763.

For more references, please see health.harvard.edu/mentalextra.

health.harvard.edu

July 2011 | Harvard Mental Health Letter | 3

When depression starts in the neck

Treating an underactive thyroid gland may improve mood.

hen someone develops neck, below the Adam's apple (a pro

depression, the brain usu trusion made of cartilage that both

ally becomes the focus of at women and men have). Although it

tention. But other organs can be the weighs less than an ounce, the thyroid

source of the problem. A common ex exerts a powerful influence throughout

ample is when the thyroid gland pro the body. It does so by secreting hor

duces too little hormone--a condition mones that affect metabolism, a chemi

known as hypothyroidism.

cal activity that controls how fast and

Nearly 10 million Americans suffer efficiently cells convert nutrients into

from hypothyroidism. The condition is energy. By regulating metabolism, the

much more common in women than thyroid indirectly affects every cell,

in men, and becomes more preva tissue, and organ in the body--from

lent with age. As many as one in five muscles, bones, and skin to the diges

women will develop hypothyroidism tive tract, heart, and brain.

by age 60.

The thyroid, in turn, is regulated by

Although researchers aren't entirely the pituitary or "master" gland. The

sure why there is a link between hypo pituitary gland (a pea-sized gland

thyroidism and depression, it is likely that sits beneath the brain) constantly

that some people are taking antidepres monitors blood levels of hormones, in

sants when they should really be tak cluding those produced by the thyroid.

ing thyroid medication. Here is a brief When blood levels of thyroid hor

review of when clinicians and patients mones fall, the pituitary gland uses

should consider hypothyroidism as a a chemical signal known as thyroid-

possible cause of low mood--and what stimulating hormone (TSH) to prompt

to do next.

the thyroid to pump up production.

In response, the thyroid uses iodine

The mighty thyroid

from food to produce two hormones.

The thyroid gland is a small butterfly- Triiodothyronine, known as T3, con

shaped structure that sits low in the tains three iodine atoms, while thyrox

Distinguishing depression from hypothyroidism*

Shared symptoms

? Depressed mood ? Reduced sexual desire

? Fatigue ? Trouble concentrating

? Weight gain

More typical of depression

? Insomnia ? Restlessness and inability to sit still ? Feelings of worthlessness ? Inappropriate guilt ? Thoughts of death or suicide ? Planning or attempting suicide

More likely hypothyroidism

? Feeling chilled or overly sensitive to

cold temperatures

? Constipation ? Muscle cramps or stiffness ? Dry skin and hair ? Hair loss ? Hoarseness ? Slowed heart rate

*Blood tests measuring thyroid function are necessary to confirm a diagnosis of hypothyroidism.

Front view Thyroid gland

Thyroid cartilage (Adam's apple)

Thyroid gland

ine, or T4, contains four. A normally functioning thyroid gland, working in conjunction with the pituitary gland, secretes T3 and T4 into the blood stream at a steady pace.

In a person with hypothyroidism, however, the thyroid gland does not fully respond to TSH, so blood levels of T3 and T4 remain low. Assuming the pituitary is functioning normally, TSH levels rise; physicians often use the TSH level to help make a diagnosis of hypothyroidism.

When thyroid hormone levels are low, many organs and internal systems slow down, creating a wide range of symp toms--including depression. People over 60 may have only one symptom-- such as mood impairment or difficulty concentrating.

Causes of hypothyroidism

Hypothyroidism often develops be cause of some underlying disease or because a medical treatment impairs thyroid function.

Autoimmune disorders. The most common cause of hypothyroidism is Hashimoto's thyroiditis, a chronic autoimmune disorder in which white blood cells make antibodies that at tack and gradually disable the thyroid gland. Another autoimmune condi tion, atrophic thyroiditis, shrinks the thyroid. Either of these conditions sig

4 | Harvard Mental Health Letter | July 2011

health.harvard.edu

nificantly reduces thyroid hormone

production.

Combining antidepressants and thyroid medications

Surgery. Partial or complete removal of the thyroid gland--whether for the treatment of thyroid cancer, an over active thyroid (hyperthyroidism, the opposite of hypothyroidism), or some other problem--permanently decreases or eliminates thyroid hormone produc

Thyroid medications are sometimes added to antidepressant treatment to improve mood--even when thyroid function is normal. Clinicians usually recommend liothyronine (T3 hormone) to augment antidepressant therapy, but in some cases they recommend levothyroxine (T4). One theory is that thyroid drugs act in concert with antidepressants in the brain. Another idea is that thyroid pills boost chemical activity in the brain, improving mood and concentration.

tion, depending on how much of the The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study

gland is removed.

evaluated the combination of T3 thyroid hormone and antidepressants in people

Radiation. Another treatment for who had not improved after two previous treatments. About 25% of those taking

an overactive thyroid, radioactive io T3 thyroid hormone saw additional improvement in their symptoms.

dine, may disable the gland, causing

permanent hypothyroidism. Likewise,

radiation treatment for Hodgkin's dis roid hormone levels to normal. Several sertraline (Zoloft)--may reduce the

ease, lymphoma, or cancers of the head options exist.

effectiveness of levothyroxine. Given

and neck may have the same effect.

Levothyroxine. The most commonly all these factors, clinicians order peri

Damage to the pituitary gland. A prescribed drug is a purified form of odic blood tests to monitor how effec

tumor, radiation, or surgery may dam synthetic T4, levothyroxine (Levo tive a thyroid medication is for each

age the pituitary gland, thus impair throid, Synthroid, others). Levothy individual, and make adjustments

ing its ability to produce and release roxine works in the same way natural based on the results.

TSH. Without this chemical signal, thyroid hormone does, provides sta Other options. Liothyronine (Cy

hormone production in the thyroid ble levels of hormone, and is well tomel), a synthetic version of T3, is

may fall.

absorbed.

eliminated from the system faster than

Medications. Some medications-- All brands are equally effective, but T4, so levels fluctuate more. Another

including the mood stabilizer each brand or generic formulation con option is liotrix (Thyrolar), which

lithium--can suppress thyroid hor tains slight variations of ingredients combines both T3 and T4 in one

mone production.

that may affect the amount of drug in pill. Both of these drugs may require

Other causes. An infection, preg the blood. The issue is not one of qual more careful dosing to avoid raising

nancy, or other conditions may cause ity, because generic drugs undergo the thyroid hormone levels too far. Yet

a temporary inflammation of the thy same potency tests that brand-name some people respond better to these

roid gland (thyroiditis). This may trig drugs do. Instead, the problem is that medications.

ger a brief period of hyperthyroidism, pharmacies may substitute one generic

followed by hypothyroidism. In some for another. Therefore it's important to Chances of recovery

cases, the thyroid never fully recov consult with your doctor if, for any rea Most people with hypothyroidism re

ers and hypothyroidism becomes son, you receive a new brand.

spond positively to treatment and find

permanent.

Clinicians determine the initial that depression and other bothersome

dose of levothyroxine based on a symptoms subside with time. How long

Diagnosing and treating

patient's weight, age, severity of hypo that takes is an individual matter, rang

hypothyroidism

thyroidism, and other medical condi ing from weeks to months. Elderly peo

Unless the pituitary gland is malfunc tions or medications. In older people, ple may take longer to respond, since

tioning, a simple blood test to mea for example, raising thyroid hormone doses of thyroid medications need to

sure TSH provides a definitive test levels too quickly may place stress on be increased slowly to avoid putting

for hypothyroidism. Typically a clini the heart--so clinicians usually begin any strain on the heart.

cian also feels a patient's neck to as with a low dose and increase it grad

sess the size of the thyroid gland and

ually. All people metabolize drugs in

Philip NS, et al. "Pharmacologic Approaches to Treatment Resistant Depression: A Re-

checks for other physical signs of hypo different ways, making the same dose examination for the Modern Era," Expert

thyroidism, such as brittle nails and more effective in one person than an Opinions in Pharmacotherapy (April 2010):

dry skin.

other. Certain medications--such as Vol. 11, No. 5, pp. 709?22.

Treatment usually involves taking a the mood stabilizer carbamazepine For more references, please see medication once a day to restore thy (Tegretol) and the antidepressant health.harvard.edu/mentalextra.

health.harvard.edu

July 2011 | Harvard Mental Health Letter | 5

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