Our Variety's Showing: A Sample of New Work

Date: December 16, 2013

A Cognitive Boost for MS?

You hear about physical losses in multiple sclerosis, yet more than half of disease sufferers also experience learning and memory problems. “It’s this cognitive impairment that leads high numbers of patients to quit their jobs,” says psychiatrist Adam Kaplin. So far, no good treatment exists for that face of MS.

Recently, however, he and Kristen Rahn reported on a novel, potential therapy that strikingly boosts cognition in mouse models of MS. What enabled the find, the researchers say, was being able to pinpoint a biochemical marker in MS patients’ brains. Using an MRI scanner primed to pick up the neurotransmitter NAAG, the Johns Hopkins team discovered that low NAAG in the right hippocampus reflects patients’ lower scores on cognitive tests.

Most exciting, Kaplin says, is work with neuropharmacologist Barbara Slusher on an agent to raise NAAG levels. After giving a NAAG-boosting drug to model mice, the researchers saw memory and learning skills rise some 200 percent, to equal that of normal, healthy animals.

Now the team aims to fine-tune the drug, with an eye to clinical trials.

For information: 410-955-2343.

 When Depression Isn’t Official

Almost 60 percent of Americans diagnosed with major depression don’t meet DSM criteria. That’s the news from psychiatrist/epidemiologist Ramin Mojtabai. He reviewed data from nearly 6,000 people in the most recent U.S. National Survey of Drug Use and Health.

“Depression over-diagnosis and over-treatment is common in this country,” Mojtabai says, “and, frankly, the numbers are staggering.”

Of further concern: The majority surveyed—including those without a lifetime history of major or minor depression—reported taking prescription psychiatric medication. “The stresses of daily life and relationships often cause upset or sadness that may not last long,” Mojtabai told The New York Times. “But Americans have become more and more willing to use medication to address them.” 

For information: 410-614-9495.

 Bright Whites a Signal for Bipolar Types?

Susan Bassett and postdoc Sarah Tighe have found an apparent matchup between MRI images of patient brains and their type of bipolar disorder. Specifically, they focused on the “white matter hyperintensities” (WMH) imaged in patients’ brains. The bright spots lie deep within the white matter and reflect circuit injury.

WMH appear in many psychiatric disorders—that keeps them from being a holy grail, a true biomarker for bipolar disorder. “But they may still be useful,” says Tighe, “in telling us the extent of illness or, perhaps, its nature.” Studies worldwide, for example, tend to tie having more WMH to severer symptoms.

The 10-member team compared MRIs of patients with bipolar disorder type I—with and without a psychosis history—and BP-II. Also studied were healthy family members and healthy unrelated people.

“WMH do appear linked to illness type,” says Bassett. Their numbers increase like so many stair steps, with healthy controls at the lowest step, then unaffected family, BP-II patients next, then those with BP-I. Finally are bipolar I patients with psychosis symptoms. More verifying is planned.

For information: 410-614-2813.

 Stressed Out in Schizophrenia?

Crucial brain changes late in adolescence enhance schizophrenia development that started before birth, psychiatrist Jennifer Coughlin explains.

Now, by analyzing the cerebrospinal fluid of patients with their first real symptoms, her team found a likely first of several biomarkers that, together, could clarify what’s going on. The researchers observed a dramatic, consistent dip in the enzyme SOD1, one that isn’t there earlier or later in the disease. SOD1 is the granddaddy of anti-oxidizing agents that the body releases to counter inflammatory processes.

 The find gives more support, Coughlin says, to the idea that inflammatory stress is important in schizophrenia. It’s a clue that patients’ neurons carry intrinsic flaws in their response to biochemical stresses that normally crop up at key developmental times. Unhindered, she adds, such stresses could dissolve synapses and disrupt circuits in a way that spells schizophrenia. 

For information: 443-287-4701.

 Smoking Cessation’s Slippery Slope

I was doing fine until I slipped and had that cigarette after dinner.

Some 95 percent of smokers who take even a few puffs early in their quit attempts relapse, studies say. The idea is that the “little slip” is ultra-pleasurable—enough to take the “ex” out of ex-smoker.

Exploring that, Erin McClure, with mentors Ryan Vandrey and Maxine Stitzer, tested the ability of varenicline to blunt the heightened enjoyment of a small lapse and so keep a person on track.

 Varenicline is a smoking cessation medication that raises long-term success two to three times more than trying to “go it alone.” Studies say it blocks or lessens nicotine’s rewarding effects and lowers craving.

In this trial, the researchers followed committed smokers, half getting varenicline and half on placebo. A two-cigarette lapse was built into the middle of a month’s quit attempt. Ultimately, the varenicline group stayed smoke-free more than twice as long as the placebo group—even with the “slip.” 

For information: 410-550-4036.

 Nosing Around a SZ Diagnosis       

Finding a telltale substance that’s highly elevated in schizophrenia patients would be a genuine diagnostic find except for the fact that it’s in patients’ brains. Only an autopsy makes a key micro-RNA accessible—too late to help anyone.

Fortunately, Shin-ichi Kano has a useful way to sample olfactory neurons in patients’ upper nasal mucosa. The nose neurons, with embryonic origins in the brain, still synapse there. Thus nose sampling opens a window on brain chemistry, Kano says.

Now, in a powerful collaboration, Israeli scientists used nasal samples collected at Johns Hopkins to detect a schizophrenia-specific micro-RNA. That makes a reasonable goal of using olfactory sampling to screen patients at high risk of schizophrenia well before their symptoms appear. One day, ideally, an early therapy will keep such patients from ever knowing the disease’s worst symptoms.

For information: 443-287-4995.

 A Rare SZ Gene

Earlier this year, Fred Nucifora’s team uncovered a rare gene mutation in a family with a high rate of schizophrenia. The find fuels the idea that various abnormal genes can advance the disease, and Nucifora says, “we may gain insight into the specific pathways involved.”

Nucifora focused on the NPAS3 gene that regulates developing neurons, especially in the hippocampus, a likely schizophrenia target. “Finding a mutation in this gene doesn’t mean it causes schizophrenia,” he says. His team has shown in the lab, however, that it does lead to abnormal neurons. Will a mouse carrying the mutated NPAS3 model schizophrenia? That’s the next step. 

For information: 410-614-0012.

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