Jake McDowell, now 10 years old and a budding author, no less, was only eight when he began to think he was going crazy.

It started when he heard that one of his Waltham classmates had an infection in his heart and needed a heart transplant.

Jake’s anxiety about his classmate grew into an overwhelming fear of germs. “He was petrified of sitting next to anybody,” even in circles of kids at school, says his mother, Debbie.

Soon, he wouldn’t sit on her lap, either. Every time he touched anyone he’d wash his hands. When his parents told him to stop, he’d try to lick his hands clean instead.

It took a year of missed diagnoses — one therapist said Jake’s troubles were due to his father’s travelling — before doctors at McLean Hospital diagnosed obsessive compulsive disorder, or OCD, and gave him drugs and behavior therapy that worked a near-miracle in ridding Jake of his fears.

For Susan Sechrist, 29, it was plain old free-floating, heart-thumping, sleep-robbing, concentration-wrecking anxiety that made life miserable. At 18, Sechrist, who lives in East Greenbush, N.Y., quit school, thinking she was “high strung and creative.”

Today, with the right diagnosis — generalized anxiety disorder, or GAD — and treatment, she’s back in college, and engaged.

Everybody gets worried from time to time, even worried enough to lose sleep or come down with a queasy stomach.

For 23 million Americans, though, anxiety is not just an occasional problem but a devastating chronic condition that takes over a person’s life, all day, every day, impairing the ability to function at home or work.

But in the last several years, scientists have made stunning progress in unravelling the biological roots of anxiety, discovering neural pathways in the brain for specific types of severe anxiety such as panic disorder, post-traumatic stress disorder and obsessive-compulsive disorder.

Partly as a result, it is now clearer than ever that “the workings of the brain are involved in all our mental life and behavior,” says Dr. Steven E. Hyman, director of the National Institute of Mental Health.

“Descartes is dead,” says Hyman. “The old mind-body distinction does nothing but get in our way. Both medications and psychotherapy are effective because they work on the brain.”

In fact, far from being emotional wimps, as laid-back folks might think, people with anxiety disorders often have identifiable — and treatable — brain disorders.

It now appears, for instance, that at least some cases of obsessive-compulsive disorder are caused indirectly by bacterial infections. And panic attacks may be triggered by an overactive “suffocation alarm” in the body.

Likewise, persistent fears, like those in panic and post-traumatic stress disorders, may stem from an overzealous amygdala, the brain’s first-response system for danger.

Joseph LeDoux, a neuroscientist at New York University and a pioneer in the study of the neural pathways, has found that, in rat brains at least, the amygdala responds much faster to fear than the cortex, or higher brain centers.

In fact, the almond-shaped amygdala acts twice as fast, probably so that animals can start a fight-or-flight response at the first hint of danger, rather than wait for the cortex to do its slower, more analytical work.

When survival is at stake, in other words, evolution has pushed the brain to “decide” that it’s better to assume instantly that a snake-like stick is a snake — rather than vice-versa — and to check it out later.

When we do see something that looks dangerous, like a snake, all the incoming signals go first to the thalamus, a kind of relay station deep in the brain, says LeDoux. The thalamus then sends signals to the visual cortex for full analysis. But it also sends signals on a fast bypass to the amygdala, which readies the body for battle or flight — firing up heart rate, breathing and muscles.

This hair-trigger reaction of the amygdala explains why we “have emotional reactions to things we don’t understand,” says LeDoux. “We respond, then we realize why we are responding.”

The amygdala’s ability to bypass the rest of the brain may underlie the fact that we often have unconscious fears that words cannot explain. This fits, says LeDoux, with the fact that in kids, the amygdala develops before the hippocampus, the brain structure that forms conscious memories.

Though not everyone agrees with this explanation, LeDoux says it also explains why “it’s possible for you to be abused as a child and have unconscious emotional memories implanted through the amygdala without ever being able to verbally understand why those fears exist.”

In other words, Freud was right. Sort of.

As Hyman puts it, “We may have long-lasting emotional memories of experiences that we can’t explicitly remember, not because we have repressed them but because the amygdala matures before the hippocampus.”

There are other examples, too, of the way our neural hard-wiring processes fear, which is defined as a response to an immediate, real situation, and anxiety, which focuses on future threats and thoughts and for which neural messages travel a somewhat different circuit, starting in the cortex and eventually feeding into the amygdala pathway.

Years ago, Dr. Michael Jenike, associate chief of psychiatry at Massachusetts General Hospital, began to suspect a biochemical basis for OCD when he found that some anti-depressant drugs helped, but not others.

Recently, PET and MRI scans of the brain have bolstered the idea that the brains of people with OCD are abnormal, says Jenike. They often have less “white matter,” the fibers that connect nerves with one another, and more “gray matter,” the nerve cell bodies, than others.

And researchers have found that when they deliberately trigger obsessions in these patients by spreading germs on their hands, the frontal lobe and the thalamus “light up” on brain scans, showing precisely which neural pathways are involved.

Even more telling, says psychologist David H. Barlow, head of the new center for Anxiety and Related Disorders at Boston University, is the finding that when obsessive-compulsive patients are treated, whether by drugs or cognitive-behavioral therapy, brain scans often go back to normal, showing that both types of therapy act on the brain.

Researchers are also closing in on some of the reasons that abnormal brain patterns in anxiety develop in the first place.

In OCD, for instance, there often appears to be damage to a brain structure called the striatum.

Recently, Dr. Susan Swedo, acting scientific director of the national mental health institute, has found that, in kids with OCD, this damage can be caused by a streptococcus infection. The body reacts to the infection by making antibodies that then attack the striatum.

Researchers have also found biological triggers for panic.

The exact cause is still unclear, but some panic attacks begin when an instability in the nervous system triggers sudden changes in heart rate that can be frightening, says Dr. David Spiegel, medical director of the BU anxiety center.

Panic attacks also occur, he says, in people who have an “overactive suffocation alarm,” a system in the brain that monitors oxygen and carbon dioxide in the bloodstream.

If carbon dioxide levels get too high, the body may interpret this as suffocation, which can trigger panic. Panic can also occur if carbon dioxide drops too low, as often happens in people who hyperventilate — that is, who breathe too fast or too deeply, as anxious people do. The result can be dizziness and other symptoms that trigger panic.

In other words, sensations from the body can be just as frightening and have the same effect as seeing a snake, says Hyman.

While finding these and other biological triggers of anxiety is a step forward, patient advocates say, many people still spend years suffering — undiagnosed — in silence.

All too often, both lay people and doctors still think that “anxiety is something you can just snap out of,” says Barlow of BU. “But people with anxiety disorders lose as much quality of life and time from work as people with chronic heart disease, lung disease and severe depression.”

In that sense, at least, Jake McDowell was relatively lucky.

For months, says his mother Debbie, Jake seemed to be getting worse. His fear of germs grew into a terror that people he loved would die. Then he became terrified of his socks because their pressure on his skin “felt like rocks,” she says.

“We’d sit with 20 pairs of socks in his room in the morning,” says Debbie. “It came to the point where he couldn’t go to school because he wouldn’t get his socks on.”

Within a week of the right diagnosis, he started a behavioral program, called exposure and response prevention therapy, through which he got a reward for wearing his socks for 15 minutes a day, then for 10 minutes more each day until his fears vanished. His progress was “remarkable,” says his mother.

Jake also began taking drugs — Anafranil and Zoloft. Today, all he takes is Zoloft, and he has learned to talk himself out of his fears. Now, says Debbie, if he gets scared someone might die, “he knows it’s OCD, and this is not necessarily going to happen.”

In fact, she says with pride, Jake now leads a normal life.

Except, of course, that he’s already written a memoir about his experiences and will speak at an upcoming conference on the disorder.

SIDEBAR 1:

All had to be perfect.

Fran Sydney of Fairfield, Conn., is 51 now and has lived with the knowledge that she has obsessive compulsive disorder for 10 years.

But she’s really had OCD since she was five, she says, though for most of this time neither she nor anyone else had the slightest idea what was the matter with her.

At first, she just had an odd tendency to stack things, “to put them in order, for symmetry, by color or whatever. Then it got worse,” she recalls.

At 15, she was in a car accident in which a boy was killed. As Sydney’s anxieties mounted, she found herself constantly “folding things perfectly, lining them up” — rituals, she now understands, that were a desperate attempt “to take away the obsessions with things being out of control,” especially the fear that people close to her would die.

At 23, she married, hoping that marriage would soothe her fears. But her first baby strangled to death during birth, the umbilical cord wrapped around his neck.

“That’s when it really took hold,” she says. “I started to get into cleanliness, along with everything else.” Her towels were perfectly folded, the labels all lined up. The house was spotless. And Sydney was terrified.

A year later, she gave birth to a child who survived, but that only seemed to make her OCD worse. “If a piece of laundry fell at the side of the washer, I’d do it over,” not because of germs, but because everything had to be perfect.

“It’s not that you just want to do this,” she says of the rituals that were taking over her life. “This is something you have to do, and if it’s not done, you feel so overwhelmed with anxiety, or this dread or whatever, that it feels like your child is running across the street and will be hit by a car.”

Still petrified that something would happen to her child, she remembers thinking, “If I have another one, I’ll be less worried.” So she had two more, but it didn’t help.

Increasingly, she’d find herself in her alphabetically-organized kitchen, trying to decide whether to put a can of green beans under “G” for green or “B” for beans. As soon as she got home from the grocery store, she’d wash everything she’d bought.

Worst of all was the effect her behavior was having on her kids and her marriage. “These kids could not do anything,” she says. “We were prisoners in the house.” Her husband left her, in large part, she says, because of her disorder.

As the kids became teen-agers, they couldn’t have friends over because Sydney felt she would have to follow the guests around, cleaning after every step.

Yet Sydney, like many people with the disorder, was able to hide her symptoms from everyone but her family.

If friends invited her over for dinner, she would not reciprocate because she couldn’t have them in her house. She even “had a best friend who didn’t know anything about this,” she says. Once, when her friend wanted to drop in spontaneously, Sydney told her she’d locked her keys in the house. “I didn’t want her to watch my rituals. I’d have to wash the floor anywhere she went. That was a real low point.”

Finally, after seeing numerous psychiatrists and psychologists who thought she was just anxious or depressed, Sydney saw a newspaper article about a double-blind study at Yale University of a new medication for obsessive compulsive disorder.

Sydney immediately recognized that OCD was her problem and sought treatment at Yale. That was 10 years ago.

As soon as she started treatment, she began to get better. She used a combination of drug therapy, with Luvox, and cognitive restructuring — a way of learning to change her thoughts to reduce anxiety.

Today, Sydney, a real estate agent, is happy, remarried, enormously proud of her kids, now 23, 25 and 27 — and pleased with herself for finally getting help.

People with OCD go undiagnosed for years, she says, from shame and because doctors do not always recognize the symptoms — like spending hours a day hand-washing or checking and re-checking repeatedly to be sure a stove is off.

Her advice is as passionate as it is hard-won: “There is hope. There’s help. The only shame is in not getting help.”

SIDEBAR 2:

TREATMENTS FOR SPECIFIC ANXIETY DISORDERS

The more researchers tease apart the subtle and not-so-subtle differences among various anxiety disorders, the better they get at fine-tuning therapy — both drugs and cognitive-behavioral treatments — to each specific problem. A primer:

– Generalized anxiety disorder (GAD) affects 7 million Americans, according to the National Institute of Mental Health, and is marked by a tendency to anticipate disaster even if there is little reason to, and to worry excessively about health, money, family or work. People with generalized anxiety often can’t relax, sleep or concentrate and have physical symptoms such as trembling and muscle tension. Unlike everyday stress, their worries seriously impair functioning at home and work. People with GAD know their anxiety is excessive; they just can’t control it.

Treatments lag behind those for other anxiety disorders. But behavioral therapy — in which a patient practices relaxation techniques and is taught other ways to cope — often helps. So does cognitive therapy, which involves working consciously to change the thoughts that trigger anxiety. Once you become conscious of the thought: “I’m going to fail this exam,” for instance, you can replace it with a more realistic one: “I’ve prepared as best I can and will probably do OK.”

Medications can also help, in particular an anti-anxiety drug called BuSpar, which is not addictive and has been proved effective in some people, and tranquilizers like Valium, Xanax and Klonopin, which are effective but cause dependence.

Other drugs also seem promising, especially a class of anti-depressants called SSRIs (for selective serotonin re-uptake inhibitors). These include Prozac, Zoloft, Paxil and Luvox.

– Obsessive compulsive disorder (OCD) causes its victims to have repeated, intrusive thoughts and perform repetitive rituals. They know their behavior makes no sense, but they cannot stop it and can spend hours every day performing rituals like handwashing. An estimated 3.9 million Americans have the disorder.

There is strong evidence that a particular behavioral treatment, “exposure and response prevention,” is effective. If a person is obsessed with germs, for instance, he lets the therapist put germs on his hands and is then taught how to manage the anxiety without compulsive, immediate handwashing.

Drugs are also effective, particularly SSRIs and a different type of antidepresssant called Anafranil. In very extreme cases, brain surgeons can relieve symptoms by making make tiny cuts in specific areas of the brain affected by OCD.

– Panic disorder, which affects 3.3 million Americans, is marked by sudden, repeated episodes of terror — panic attacks. Physical symptoms include chest pain, heart palpitations, shortness of breath, dizziness, feelings of unreality and fear of dying.

In addition to the immediate terror, panic attacks can also leave a person with a phobia about the place where attacks occurred, such as a theater or shopping mall.

Panic attacks can also leave people terrified of anything — like sex, exercise or caffeine — that also causes a rapid heart beat or other disturbing physical sensations.

Panic attacks respond well to cognitive-behavior therapy, including a new variant called interoceptive exposure in which the therapist induces the physical sensations associated with panic, like dizziness, and the patient learns to reinterpret these as signs of anxiety, not of imminent death.

Phobias related to panic disorder can be effectively treated with exposure therapy, in which a patient is exposed to the terrifying place or object and taught not to fear it.

Drugs also work well, including high doses of tranquilizers. But increasingly, doctors favor SSRIs instead, because they have few side effects and don’t cause dependence. They sometimes also use an antidepresssant called Tofranil.

• Phobias, which affect 7.2 million Americans, are extreme, disabling and irrational fears of something or some place that poses little actual danger. The fear leads to extreme avoidance of objects or situations, making some people housebound.
• Drugs are not very effective against phobias, but cognitive-behavioral therapy often works, especially “exposure” therapy.
• Post-traumatic stress disorder (PTSD) is marked by persistent nightmares, flashbacks, numbed emotions and a tendency to startle easily. PTSD can follow many traumatic experiences, including rape, war, child abuse, natural disasters or being taken hostage, and 5.7 million Americans are thought to be affected.

As with GAD, treatment options have lagged behind those for other anxiety disorders, but cognitive-behavioral therapy can help, as can group psychotherapy. Several antidepresssants have been tried, but none has proved universally effective.

SIDEBAR 3:

For general information on anxiety, call:

• 1-888-8-ANXIETY. (You don’t have to dial the `y’ to get through.)
• The Center for Anxiety and Related Disorders at Boston University: 617-353-9610.

For information on OCD:

• 1-800-NEWS-4-OCD (a hotline operated by Solvay Pharmaceuticals, Pharmacia & Upjohn, which make and distribute Luvox.)
• Web site: http://www.ocdresource.com\

You can also contact the following organizations:

• Anxiety Disorders Association of America, Dept. A, 6000 Executive Blvd., Suite 513, Rockville, MD 20852. Tel.: 301-231-9350.
• Freedom from Fear, 308 Seaview Ave., Staten Island, NY 10305. Tel. 718-351-1717.
• National Anxiety Foundation, 3135 Cluster Dr., Lexington, KY 40517-4001. Tel.: 606-272-7166.
• Obsessive-Compulsive (OC) Foundation, Inc., P.O. Box 70, Milford, CT 06460. Tel.: 203-878-5669.
• American Psychiatric Association, 1400 K St. NW, Washington, DC 20005. Tel.: 202-682-6220.
• American Psychological Association, 750 1st St. NE, Washington, DC 20002-4242. Tel.: 202-336-5500.
• Association for Advancement of Behavior Therapy, 305 7th Ave., New York, NY 10001. Tel.: 212-647-1890.
• National Alliance for the Mentally Ill, 200 N. Glebe Rd., Suite 1015, Arlington, VA 22203-3754. Tel.: 800-950-NAMI (950-6264).
• National Institute of Mental Health:

Toll-free information services:

• Depression: 1-800-421-4211
• Panic and Other Anxiety Disorders: 800-647-2642.
• National Mental Health Association, 1201 Prince St., Alexandria, VA 22314-2971. Tel.: 703-684-7722.
• National Mental Health Consumers’ Self-Help Clearinghouse, 1211 Chestnut St., Philadelphia, PA 19107. Tel: 800-553-4539.
• Phobics Anonymous, P.O. Box 1180, Palm Springs, CA 92263. Tel.: 619-322-COPE (332-2673).
• Society for Traumatic Stress Studies, 60 Revere Dr., Suite 500, Northbrook, IL 60062. Tel.: 847-480-9080.