Brain scans
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John McManamy
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Carol Tamminga MD, of the University of Texas Southwestern Medical Center at on Amazon
Disorder Source
Dallas, told a seminar at the 2003 NAMI convention how she and her colleagues
eagerly waited outside the door in anticipation of viewing their first brain scans of
a patient with schizophrenia. Much to their dismay, the images looked normal,
Knowledge is
which was their first lesson in the art of subtlety.
A study by Ahmad Hariri PhD et al of the NIMH appearing in the July 19, 2002 Research may lead
Science divided 28 subjects into two groups, those who had a short form (allele) to diagnosis.
of the serotonin transporter gene SLC6A4, and those with the long allele. Cellswith the long variant express nearly double the serotonin reuptake as those withthe short allele. The subjects were placed in an MRI machine and completed a "Dr Tamminga
simple exercise involving processing the images of three different faces. The brain used before and
scans revealed that those with the short allele displayed a significantly greater after PET scans to
response in the right amygdala while engaged in the task. The amygdala is a tiny, track Haldol and
almond-shaped part of the brain which governs fear. When the subjects were Clozaril at work."
given a thinking task not involving emotions, no variants were seen.
In the authors’ words: "Our results directly implicate a genetically determined link Your online source for
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between serotonin transporter function and the response of brain regions criticalfor emotion processing." For free samples, email
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This may very well be the first study linking genes to emotions in humans, and it the heading and your
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certainly won’t be the last, thanks to our increasing ability to literally peer inside Science Articles
the skull and view what is taking place.
Find out more.
Brain Science 101
Perhaps the number one question about brain scans concerns whether it will be
possible to use the technology to diagnose depression or bipolar disorder. The
short answer is maybe. In early 2002, a possible taste of the future occurred in a Bookstore
Washington DC courtroom when plaintiff Jane Fitts successfully used brain scans showing an atrophied parietal lobe and other abnormalities to convince a federal Shop for depression and
bipolar books online

judge that her bipolar disorder was "physical" in nature, thus allowing her to accrue extended disability according to the terms of her health plan (see article).
The technology we have may already be sufficient to make a diagnosis. What islacking is our knowledge of what makes a particular brain abnormality unique to a certain illness. But that may change, with researchers increasingly turning to brainscans to discover how we tick.
Positron emission tomography (PET) involves the subject inhaling or being
injected with radioactive tracers, which are absorbed into the brain tissue. A positively-charged particle (positron) collides with an electron in the tissue, destroying both and resulting in two photons that are detected by the PETscanners. Increases or decreases in cerebral blood flows to and from regions of the brain are measured by radiation counts.
Dr Tamminga is the author of a classic 1992 study involving PET scans on 12 patients with schizophrenia, which identified functional abnormalities in their limbiccircuits compared with normal controls. In a study published in 2003, Dr Tamminga used before and after PET scans to track Haldol and Clozaril at work,finding both similarities and differences in blood flows to certain regions of the brain that could account for their clinical benefits and side effects.
A pioneering study by Baxter et al using PET to measure resting glucose
metabolism in patients with unipolar, bipolar, and secondary depression found low metabolism in the dorsal anterior prefrontal cortex, which increased when theirdepression was treated (March 1989 Archives of General Psychiatry, Vol 46 No 3). Succeeding studies have implicated abnormal activity in other areas of thefrontal cortex and the amygdala.
A 1997 study by Helen Mayberg MD of the University of Texas Health Center, San Antonio et al used PET scans to find that the rate of metabolism in the anteriorcingulate accurately predicted treatment response or nonresponse in depressed patients (March 1997 NeuroReport). In a study published in the May 2002 American Journal of Psychiatry, using the same technology, Dr Mayberg foundthat both antidepressant and placebo responders experienced the same reactions in the cortex and limbic regions of the brain, but those taking antidepressants alsoexperienced unique changes in the brainstem, striatum, and hippocampus.
Other Science
A study published in the October 2000 AJP used PET scans to find that peoplewith bipolar I have 30 percent more monoamine releasing cells, which send the neurotransmitters serotonin, dopamine, and norepinephrine into the brain. "To putit simply," explained the study’s lead author Jon-Kar Zubieta MD, PhD in a press release, "these patients' brains are wired differently, in a way that we mightexpect to predispose them to bouts of mania and depression." Progress or

Through PET scans, we have learned that the therapeutic dose for anantipsychotic medication occurs when approximately 65 percent of the brain’s dopamine D2 receptors are occupied and that their notorious side effects begin tohappen when the 80 percent threshold is crossed, thus giving physicians a clear picture of how to accurately dose their patients. We are also learning about how experimental drugs bind to their intended targets. Merck used PET scans to itsbenefit in determining that its substance P antagonist (on the market as Emend for chemo-induced nausea but which failed clinical trials for depression) achieved 90 Advancing to 1948
percent occupancy on the brain's NK1 receptors.
Single photon emission computed tomography (SPECT) is similar to PET in
that it is sensitive to radioactive tracers absorbed into the brain, this time coming
from the emission of photon gamma rays. It is the older technology and is seldom
used today. Both PET and SPECT allow the brain to be viewed as it is actually
functioning - thinking, remembering, experiencing pain or pleasure, and so on. This
functioning is interpreted by PET in brilliant hues that psychiatrists can show to
their patients to dramatize mental illness at work.
Gunnar Heuser MD, PhD of UCLA has been using a hyperbaric chamber on thoseexposed to neurotoxins, including several who manifested ADD. Of 10 patients hetreated for toxic encephalopathy (which results in cognitive and memoryimpairment), eight showed significant improvement and two marginal improvementon cognitive tests. Before and after SPECT imaging revealed marked reduction inblue and violet areas - signifying a return of more normal blood flow - in the brain.
Magnetic resonance imaging (MRI) essentially takes pictures of the brain's
water. As opposed to PET scans, MRIs do not require radioactive tracers and
thus can be used repeatedly on subjects. Instead, these scanners are sensitive to
oxygen, which is released from hemoglobin when blood flow to various parts of
the brain is increased. MR spectroscopy measures the chemistry of the brain
while fMRI (functional MRI) measures activity (with subjects performing tasks
during the scan). The standard strength of an MRI is 1.5 Tesla, with newer
machines capable of achieving much higher resolution at three, four, seven, and
9.4 Tesla. At four Tesla, for instance, an MRI can separate glutamate from
Kevin Lim MD of the University of Minnesota is using a novel MR method, diffusiontensor imaging (DTI) to produce images of white matter in the brains of subjectswith schizophrenia and geriatric depression. The white matter takes the shape offine fibers that run like wiring beneath the cortex. Lesions in white matter havebeen identified in age-related illnesses such as dementia, and are the increasing
focus of investigation in mental illnesses.
Gerard Sanacara MD, PhD of Yale has used magnetic resonance spectroscopyto measure the neurotransmitter GABA in the brain, finding that those withmelancholic depression show low GABA concentrations in the occipital cortex,while the depletion is not as pronounced for those with atypical depression,indicating a diagnostic potential for subtypes of depression (March, 2003 AJP).
Before and after scans of eight patients who had ECT found a doubling of GABA,and similar scans of patients on SSRIs showed a slow rise in GABA levels in nineof 11 of them.
The next time you encounter a skeptic who tells you your illness is all in your head,you may want to download and print brain scans and keep them handy for futureencounters. At the very least, these images eloquently portray in a way thatwords cannot that our illness is demonstrably real.
For free online issues of McMan's Depression and Bipolar Weekly, email me andput "Sample" in the heading and your email address in the body.
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