Volume 16, Number 2
Transverse Myelitis and Depression:
Ties That Bind
New studies not only improve treatment, but may lead to a psychiatric holy grail.
At a local symposium on transverse myelitis (TM), clinicians Adam Kaplin, M.D., Ph.D., and Douglas Kerr, M.D., Ph.D., calmly fielded patients' questions about the illness -- it arises when patches of the spinal cord are acutely inflamed. In some patients, TM is mild or fleeting. Others become numb, incontinent, unable to walk and plagued by urges to urinate.
But
the two weren't prepared for a young woman with only the mildest of sensory
upsets who approached them late in the day, overwhelmed, she said, by the
disease. She'd sold her belongings and stockpiled lethal doses of drugs.
And, rattled by seeing patients who, though physically worse, "were nowhere
near" her level of despair, she was going home, she said, to kill herself.
"We threw her in the back of my car," says psychiatrist Kaplin, "hurried to Hopkins, and waited until she was admitted and treated."
And though startled, neither doctor was surprised: Their patient encounters at Hopkins' transverse myelitis clinic, which neurologist Kerr founded, have long suggested TM and depression go hand in hand-more so, even, than multiple sclerosis, which carries a 60 percent chance of the mood illness. Now their new study confirms that.
In work Kaplin led, the researchers monitored TM patients, comparing their mood with both MS patients and other controls. Also, because thought processes act like miners' canaries in reflecting slight perturbations in the brain, patients also underwent cognitive testing.
"We'd assumed people were depressed because they were demoralized. Who wouldn't be upset by incontinence and motor losses?" asks Kaplin. "But with TM, as in multiple sclerosis, our studies showed a clear mismatch between how depressed and how physically disabled people were. That says depression's inherent in the disease." The research also disclosed subtle cognitive problems, such as difficulties patients have in shifting from one task to another.
Yet when Kaplin suggested that meant TM must target brain tissue as well as spinal cord, "I told him, hogwash," says Kerr. "Transverse myelitis patients have normal brain MRIs. And unlike multiple sclerosis patients, their scans show no lesions in the brain."
But
Kaplin believes immune chemistry gone awry can trouble the brain enough
to alter mood without killing cells. For example, cancer patients on treatment
with a specific cytokine-a type of immune messenger-become severely depressed.
Cytokine-treated lab rats stop socializing; they give up sex; they won't
press the treat lever. Also, the molecules can overstimulate the HPA axis,
a brain pathway tied to depression. "We think cytokines may mediate autoimmune
depression."So, along with neuropsychological testing, the researchers have been sampling patient blood and spinal fluid for 40 different cytokines to see if a pattern emerges. Early work suggests levels climb-in some cases three hundredfold higher than controls-as TM becomes more aggressive.
What has Kaplin holding his breath is the possibility this work approaches one of psychiatry's holy grails-finding an unambiguous human model of depression.
To offer TM as a biological model of mental illness takes more than matching high cytokines with patients' being pathologically glum, says Kaplin. "We need to show real changes in brain biology." To that end, they'll soon add brain neurochemistry scans to the patient profile (see page 3). "If we find that high cytokines perturb the brain's metabolism in specific ways that lead to depression, we'll have our model."
For more information, call 410-955-6114.