[Paleopsych] NYT: Can Brain Scans See Depression?

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Wed Oct 19 01:50:04 UTC 2005

Can Brain Scans See Depression?


    They seem almost alive: snapshots of the living human brain.

    Not long ago, scientists predicted that these images, produced by
    sophisticated brain-scanning techniques, would help cut through the
    mystery of mental illness, revealing clear brain abnormalities and
    allowing doctors to better diagnose and treat a wide variety of
    disorders. And nearly every week, it seems, imaging researchers
    announce another finding, a potential key to understanding depression,
    attention deficit disorder, anxiety.

    Yet for a variety of reasons, the hopes and claims for brain imaging
    in psychiatry have far outpaced the science, experts say.

    After almost 30 years, researchers have not developed any standardized
    tool for diagnosing or treating psychiatric disorders based on imaging

    Several promising lines of research are under way. But imaging
    technology has not lived up to the hopes invested in it in the 1990's
    - labeled the "Decade of the Brain" by the American Psychiatric
    Association - when many scientists believed that brain scans would
    turn on the lights in what had been a locked black box.

    Now, with imaging studies being published at a rate of more than 500 a
    year, and commercial imaging clinics opening in some parts of the
    country, some experts say that the technology has been oversold as a
    psychiatric tool. Other researchers remain optimistic, but they wonder
    what the data add up to, and whether it is time for the field to
    rethink its approach and its expectations.

    "I have been waiting for my work in the lab to affect my job on the
    weekend, when I practice as a child psychiatrist," said Dr. Jay Giedd,
    chief of brain imaging in the child psychiatry branch at the National
    Institute of Mental Health, who has done M.R.I. scans in children
    Monday through Friday for 14 years. "It hasn't happened. In this
    field, every year you hear, 'Oh, it's more complicated than we
    thought.' Well, you hear that for 10 years, and you start to see a

    Psychiatrists still consider imaging technologies like M.R.I., for
    magnetic resonance imaging, and PET, for positron emission topography,
    to be crucial research tools. And the scanning technologies are
    invaluable as a way to detect physical problems like head trauma,
    seizure activity or tumors. Moreover, the experts point out, progress
    in psychiatry is by its nature painstakingly slow, and decades of
    groundwork typically precede any real advances.

    But there is a growing sense that brain scan research is still years
    away from providing psychiatry with anything like the kind of clear
    tests for mental illness that were hoped for.

    "I think that, with some notable exceptions, the community of
    scientists was excessively optimistic about how quickly imaging would
    have an impact on psychiatry," said Dr. Steven Hyman, a professor of
    neurobiology at Harvard and the former director of the National
    Institute of Mental Health. "In their enthusiasm, people forgot that
    the human brain is the most complex object in the history of human
    inquiry, and it's not at all easy to see what's going wrong."

    For one thing, brains are as variable as personalities.

    In a range of studies, researchers have found that people with
    schizophrenia suffer a progressive loss of their brain cells: a
    20-year-old who develops the disorder, for example, might lose 5
    percent to 10 percent of overall brain volume over the next decade,
    studies suggest.

    Ten percent is a lot, and losses of volume in the frontal lobes are
    associated with measurable impairment in schizophrenia, psychiatrists
    have found. But brain volume varies by at least 10 percent from person
    to person, so volume scans of patients by themselves cannot tell who
    is sick, the experts say.

    Studies using brain scans to measure levels of brain activity often
    suffer from the same problem: what looks like a "hot spot" of activity
    change in one person's brain may be a normal change in someone else's.

    "The differences observed are not in and of themselves outside the
    range of variation seen in the normal population," said Dr. Jeffrey
    Lieberman, chairman of the psychiatry department at Columbia
    University Medical Center and director of the New York State
    Psychiatric Institute.

    To make matters even more complicated, many findings are disputed. In
    people with severe depression, for instance, researchers have found
    apparent shrinkage of a part of the temporal lobe called the
    hippocampus, which is critical for memory. But other investigators
    have not been able to replicate this finding, and people with injuries
    to the hippocampus typically suffer amnesia, not depression,
    psychiatrists say.

    For problems like attention-deficit disorder and bipolar disorder, the
    experts say, psychiatrists have much less research on which to base
    their theories.

    Most fundamentally, imaging research has not answered the underlying
    question that the technology itself has raised: which comes first, the
    disease or the apparent difference in brain structure or function that
    is being observed?

    For a definitive answer, researchers would need to follow thousands of
    people from childhood through adulthood, taking brain scans regularly,
    and matching them with scans from peers who did not develop a
    disorder, experts say. Given the expense and difficulty, such a study
    may never be done, Dr. Hyman said.

    One investigator has used imaging research to fashion a small,
    experimental psychiatric treatment.

    In a series of studies of people with severe depression, Dr. Helen
    Mayberg, a professor of psychiatry at Emory University in Atlanta,
    found a baffling pattern of activity.

    Using PET scanning technology, Dr. Mayberg found sharp dips and spikes
    of activity in about a half-dozen areas of these patients' brains as
    their moods improved while they were taking either antidepressant
    drugs or placebos.

    The changes were similar in all patients, but it was difficult to tell
    how the scattering of the dips and spikes were related.

    By analyzing the peaks and valleys on the scans as part of a circuit -
    networked together, like a string of Christmas lights - Dr. Mayberg
    found that one spot in particular seemed to modulate the entire
    system, like a transformer or a dimmer.

    She confirmed the importance of this spot, called Brodmann area 25, by
    scanning the brains of mentally healthy people while they remembered
    painful episodes from their lives: while sad they, too, showed
    increased activity in this area.

    In March, Dr. Mayberg and a team based at the Rotman Research
    Institute in Toronto reported on six patients who had had electrodes
    implanted in their brains next to Brodmann area 25.

    All had been severely depressed for at least a year, and they had
    responded poorly to available therapies. The implanted electrodes,
    often used to treat Parkinson's disease, produce a current that slows
    neural activity, for reasons scientists do not yet understand.

    So far, the researchers reported in the journal Neuron, four of the
    six people have shown significant and lasting recovery; all four are
    still on antidepressant drugs but at reduced doses. And all four have
    returned to work or their usual routines, Dr. Mayberg said.

    The widely reported experiment has generated more than 300 requests
    from people to be considered for the operation, she added.

    "It's very important to understand that this is experimental, and the
    next step is to replicate what we did, with a placebo, and that could
    send us right back to the drawing board," Dr. Mayberg said in an

    The findings so far are encouraging, she said, "but the idea that this
    is something for every severely depressed patient - well, shame on us
    if we suggest that. The brain is a very big place and we had better
    have a very good idea of what we're doing before holding this out as a

    Many people would rather not wait for the science of imaging to
    mature, however. At clinics in California, Washington, Illinois, Texas
    and elsewhere, doctors offer brain scans to people with a variety of
    conditions, from attention-deficit hyperactivity disorder, often
    called A.D.H.D., to depression and aggressive behavior.

    Dr. Daniel Amen, an adult and child psychiatrist based in Newport
    Beach, Calif., said he performed 28,000 scans on adults and children
    over the past 14 years, using a technique called Spect, or single
    photon emission computed tomography.

    In an interview, Dr. Amen said that it was unconscionable that the
    profession of psychiatry was not making more use of brain scans. "Here
    we are, giving five or six different medications to children without
    even looking at the organ we're changing," he said.

    He said the scans had helped him to distinguish between children with
    attention deficit problems who respond well to stimulants like Ritalin
    and those who do poorly on the drugs. In a series of books and medical
    articles, Dr. Amen argued that the images helped convince people that
    the behavior problems had a biological basis and needed treatment,
    with drugs or other therapies.

    "They increase compliance with treatment and decrease the shame and
    guilt" associated with the disorders, he said.

    At the Brainwaves Neuroimaging Clinic in Houston, doctors use the
    scans to diagnose and choose treatment for a range of psychiatric
    problems, according to a clinic spokeswoman. And a variety of doctors
    advertise the imaging services, particularly for attention-deficit
    disorder, on the Internet. But the experts who study imaging and
    psychiatry say there is no evidence that a brain scan, which can cost
    more than $1,000, adds significantly to standard individual
    psychiatric exams.

    "The thing for people to understand is that right now, the only thing
    imaging can tell you is whether you have a brain tumor," or some other
    neurological damage, said Paul Root Wolpe, a professor of psychiatry
    and sociology at the University of Pennsylvania's Center for

    He added, "This imaging technology is so far from prime time that to
    spend thousands of dollars on it doesn't make any sense."

    The big payoff from imaging technology, some experts say, may come as
    researchers combine the scans with other techniques, like genetic or
    biochemical tests. By radioactively marking specific receptors in the
    brain, for example, researchers are using brain scans to measure how
    brain chemicals known to affect mood, like dopamine, behave in people
    with schizophrenia, compared with mentally healthy peers.

    Imaging researchers are also studying depression-related circuits to
    see how they may arise from genetic variations known to put people at
    risk for depression.

    And as always, the technology itself is improving: a new generation of
    M.R.I. scanners, with double the resolution power of the current
    machines, is becoming more widely available, Dr. Lieberman said.

    "With increased resolution, we'll be able to do more sensitive and
    more precise work, and I would not be surprised if anatomy alone based
    on volume will be a diagnostic feature," he said. "We have gained an
    enormous amount knowledge from thousands of imaging studies, we are on
    the threshold of applying that knowledge, and now it's a matter of
    getting over the threshold."

    But for now, neither he nor anyone else can say when that will happen.

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