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Credit: Massachusetts General Hospital

An automated health-care interface aims to streamline preventative screening.

MIT Technology Review, February 26, 2009, by Lauren Gravitz — A computerized kiosk under development at Massachusetts General Hospital (MGH) can take a patient’s medical history, weight, pulse, blood pressure, and other vital signs, and even perform simple blood tests for glucose and cholesterol. Physicians hope that the device, slated to begin field testing in the United Kingdom in June, will one day bring relief to the overburdened healthcare system, and allow doctors to intervene earlier in chronic disease.

Doctors’ appointments in the United States often feel like more of an inconvenience than a help, both for patients, who can spend hours in waiting rooms, and doctors, who spend hours filling in charts and organizing patient information. Ronald Dixon, director of the Virtual Practice Project, imagines that his kiosk–a small, Windows-based desktop computer with just a few peripherals–could one day revolutionize doctors’ visits just as ATMs transformed banking. By removing the tellers from the interactions that could be easily automated, banks saved face-to-face contact for more complex transactions. Dixon, who’s also a primary-care physician at MGH, believes that the same could be done for doctors.

The kiosk consists of a tabletop computer and a number of peripherals–a blood-pressure cuff, a scale, a pulse oximeter to measure blood oxygen levels, and a peak-flow meter to determine whether someone’s airways are constricted–as well as a blood-testing device commonly used in emergency rooms that can measure cholesterol and glucose levels. (The current version requires a trained assistant to do the finger stick for blood collection, although future versions will be automated.)

Ideally, Dixon envisions his kiosks placed in supermarkets and big-box stores: customers could step up, key in their password-protected information, answer questions related to their personal health history, and then get their checkup. “The results would then go to your provider, and that provider sends a message back to you the way you want it–either through e-mail or texting–about what to do with that result,” he says. It could determine whether current medications are doing their job, whether a particular strategy is working or changes need to be made, and whether a more in-depth exam is necessary.

In June, the kiosk will get its first glimpse at prime time. A pilot version will be tested in stores and other public spaces in Britain as part of a newly established vascular screening program to prevent cardiovascular disease, stroke, and heart attack. The United Kingdom is an ideal testing ground because it has a nationalized health-care system: everyone has an assigned primary-care physician and electronic health records, so the infrastructure for sharing and responding to the results is already in place.

“They’re trying to catch people who typically don’t get screened, since a lot of the population doesn’t go to the doctor unless they’re sick,” Dixon says. “But everyone goes to the drugstore or grocery store once in a while.” A 10-minute interaction will include a blood-pressure check, combined with blood glucose and cholesterol screens. The information can then be sent off to a central database. Those residents at highest risk for disease will receive a phone call from their physician.

While some might worry that the kiosk will perform medical care best left in the hands of a doctor, Dixon notes that it’s not geared to diagnosis: the machine is designed to collect and relay test information in a much more streamlined fashion than that used today. And it is targeted, at least in part, to patients who might not otherwise visit a doctor’s office.

The ability to efficiently screen for and monitor chronic diseases, such as diabetes and hypertension, whose rates are predicted to rise over the next 10 to 20 years, will be especially important. “Treatment for these should be very streamlined to make sure that people are on the medicines they need to be,” says Kristian Olson, a pediatrician at MGH involved in global-health initiatives. “And all of that should be routinized as much as possible, or else you’re reinventing the wheel for each patient.”

Other physicians familiar with the project have created their own visions for how the kiosk might be used. “A trip to the doctor’s office is a fairly clunky process,” says David Howes, president, chief medical officer, and CEO of Martin’s Point Health Care, based in Maine and New Hampshire. “It takes a lot of effort, it takes a lot of time, and it doesn’t really use the time of high-paid specialized professionals in the best possible way.”

Howes believes that just placing versions of Dixon’s kiosk in doctors’ offices could streamline the process and completely change primary care for both patients and their physicians. “Think about your process of going to the doctor: you go in, the nurse sits down with you, takes a lot of history, takes vitals, and might even order some lab studies. And then the physician comes in and replicates a lot of that work,” he says.

But a kiosk would allow for much of that to be accomplished before a patient ever sits down in an exam room. “By the time you get in to see the physician, the information has been gathered and organized,” Howes says. A clinician can look at the information and determine what conversations she and the patient need to have. “We’ve daydreamed that a tool like this, in the intake process, would be very useful.”

An automated system like the health kiosk could also be used to extend health-care access to the poorest nations. “It’s clear that there’s a human-resource limitation overseas that’s far larger than what we have in this country,” says MGH’s Olson. The kiosks, in combination with just a single physician or nurse practitioner, “could provide common care to a huge percentage of people,” he says.

In developing nations, Olson views the kiosk as less of a preventative screening tool than one that could be used for vital follow-ups. “I could see it being incredibly useful for routine follow-up for patients with issues such as tuberculosis or HIV,” he says. “It’s a way to follow up with physicians, demonstrate side effects, talk about whether [patients are] taking their meds.”

George Whitesides has created a cheap, easy-to-use diagnostic test out of paper.

MIT Technology Review, March/April 2009, by Kristina Grifantini — Diagnostic tools that are cheap to make, simple to use, and rugged enough for rural areas could save thousands of lives in poor parts of the world. To make such devices, Harvard University professor George Whitesides is coupling advanced microfluidics with one of humankind’s oldest technologies: paper. The result is a versatile, disposable test that can check a tiny amount of urine or blood for evidence of infectious diseases or chronic conditions.

The finished devices are squares of paper roughly the size of postage stamps. The edge of a square is dipped into a urine sample or pressed against a drop of blood, and the liquid moves through channels into testing wells. Depending on the chemicals present, different reactions occur in the wells, turning the paper blue, red, yellow, or green. A reference key is used to interpret the results.

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Color change: Paper tests, such as those shown here, could make it possible to diagnose a range of diseases quickly and cheaply. A small drop of liquid, such as blood or urine, wicks in through the corner or back of the paper and passes through channels to special testing zones. Substances in these zones react with specific chemicals in the sample to indicate different conditions; results show up as varying colors. These tests are small, simple, and inexpensive.

Credit: Bruce Peterson

“Pill ID”

MIT Technology Review, March/April 2009, by TR Editors — To deter the theft and counterfeiting of medication, NanoGuardian has developed a way to apply nanoscale patterns to individual pills and capsules so that they can be authenticated or traced. The company won’t say how the technology works but claims that the mechanism for producing the pattern can be built into a capsule mold. Detection of the nano pattern has to be performed by NanoGuardian itself, using proprietary means. The technology has been approved by the U.S. Food and Drug Administration for use by a NanoGuardian client.

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What is Nanoguardian?

NanoGuardian provides a state-of-the-art, nanotechnology-based defense against pharmaceutical counterfeiting and illegal diversion.

Utilizing a patented NanoEncryption™ process, NanoGuardian delivers true forensic, multilayered authentication and tracing capability on each and every dose.

In the NanoEncryption process, NanoCodes are incorporated directly onto tablets, capsules and vial caps. These codes may be associated with an unlimited amount of manufacturer-determined data, including product information (strength and expiration date), manufacturing information (location, date, batch and lot number) and distribution information (country, distributor, wholesaler and chain).

Where Nanoguardian Works

NanoGuardian was first introduced as a solution for the pharmaceutical supply chain, which is estimated to suffer more than $35 billion1 in lost revenue a year.

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NanoGuardian’s NanoCodes can also be linked to on-package e-pedigree technologies such as radio frequency identification (RFID) and 2-D barcodes, creating a true multilayered protective shield of each individual dose from plant to patient. At the overt level, a simple field inspection can reveal if a dose is authentic. The forensic-level NanoCodes, however, can only be detected with highly specialized, proprietary tools within NanoGuardian’s Product Integrity Centers, enhancing the unrivaled security of the NanoGuardian process.

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But in fact, counterfeiting and illegal diversion plague industries throughout the world, with counterfeit currency, bogus credit cards and fake watches as widely cited examples. Less publicized is the widespread counterfeiting of auto and aircraft parts, medical devices, software, luxury goods, ID cards, passports and more.

Fortunately, the NanoGuardian process provides authentication and traceability of a product, at the unit level, throughout the supply chain. If you’re curious as to whether NanoGuardian could play a role in securing and protecting your brand, please go to the Contact Us section of this site.

1 The Center for Medicines in the Public Interest

Closed-Loop Protection

Once NanoGuardian’s NanoEncryption technology is fully implemented for a particular product or products, you can take advantage of NanoGuardian’s Closed-Loop Protection™ offering.

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Closed-Loop Protection combines the dual-protective benefits of NanoEncryption™ technology with a proactive market-monitoring program, creating an “early warning” system in the fight against counterfeiting and diversion. This results in reduced risk to brands, companies and patients.

Whether global or regional in scope, Closed-Loop Protection allows you to proactively focus brand protection efforts wherever in the world you suspect counterfeiting or diversion. With Closed-Loop Protection, NanoEncrypted doses are authenticated within 24 hours of receipt, exposing the counterfeits. And because of the specific distribution data associated with NanoGuardian’s forensic-level NanoCodes, you will immediately know of any dose that is not precisely where you intend it to be. Before NanoGuardian, brand-protection technology so revealing simply didn’t exist.

NanoGuardian protects returned goods. The appearance of counterfeit and diverted product in the returns side of the supply chain is escalating. In fact, it is not uncommon for counterfeit and diverted product to be found in genuine packaging. NanoGuardian enables manufacturers and returned goods agents to quickly and easily authenticate returns within minutes, and do so with relatively inexpensive and readily available tools.

Samples of returned product can be quickly analyzed at a NanoGuardian Product Integrity Center, providing a means of detecting diverted product “laundered” through the returned goods process and bringing a stop to this costly problem.

NanoGuardian can validate adverse events. When non-typical adverse events are reported, NanoGuardian can be used to authenticate the product in question and potentially save your brand from erroneous adverse label changes that reduce its competitiveness.

February 26, 2009 — Researchers at the University of Pennsylvania School of Medicine, in Philadelphia, have discovered stem cells in the esophagus of mice that are able to grow into tissue-like structures and form parts of an esophagus lining when placed into immune-deficient mice.1

“The immediate implication is that we’ll have a better understanding of the role of these stem cells in normal biology, as well as in regenerative and cancer biology,” stated senior author Anil Rustgi, MD, professor of medicine and genetics and chief of gastroenterology at Penn. “Down the road we will develop a panel of markers that will define these stem cells and use them in replacement therapy for diseases like gastroesophageal reflux disease [GERD] and to understand Barrett’s esophagus, a precursor to esophageal adenocarcinoma, and how to reverse that before it becomes cancer.”

Diseases of the esophagus are very common, both in the United States and worldwide. “Benign forms include GERD, and millions are affected,” Dr. Rustgi noted.

GERD sometimes can lead to esophagitis, an inflammation of the esophagus. “In some of these cases, esophagitis can lead to a swapping of the normal lining of the esophagus with a lining that looks more like the intestinal lining. That’s called Barrett’s esophagus,” he explained. “This can lead to cancer of the esophagus, which is the fastest rising cancer in the United States, increasing by 7 percent to 8 percent a year.”

To understand normal biology and how injured cells may one day be repaired, researchers set out to identify potential stem cells, which have the ability to self-renew, in the esophagus and to characterize them. The first step was to grow mouse esophageal cells they suspected were adult stem cells. The cells formed colonies that self-renewed, then they grew into esophageal lining tissue in a three-dimensional culture apparatus.

“These tissue culture cells formed a mature epithelium sitting on top of the matrix,” said Dr. Rustgi. “The whole construct is a form of tissue engineering.”

The investigators then tested their pieces of esophageal lining in animals. When the tissue-engineered patches were transplanted under the skin of immunodeficient mice, the cells formed epithelial structures.

In addition, green-stained stem cells in a mouse model of esophageal injury, which mimics what happens during acid reflux, migrated to the injured lining cells and co-labeled with the repaired cells. This indicated involvement of the stem cells in tissue repair and regeneration.

The researchers eventually will develop genetically engineered mouse models to be able to track molecular markers of esophageal stem cells found in a microarray study. The group already has developed a library of human esophageal cell lines and is looking for human versions of markers already identified in mice.

“The ultimate goal is to identify esophageal stem cells in a patient, grow the patient’s own stem cells, and inject them locally to replace diseased tissue with normal lining,” said Dr. Rustgi.

The Penn scientists collaborated with researchers from Massachusetts General Hospital, in Boston, and the Wistar Institute in Philadelphia. The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute.

Reference

1. Kalabis, J., Oyama, K., Okawa, T., et al. (2008). A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. Journal of Clinical Investigation, 118 (12): 3860-69.

A British company has demonstrated an important step for a new sequencing technique.

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A DNA base (red) passes through a protein tunnel lined with a sugar (blue and green bubbles). The sugar slows down the DNA as it moves through the pore, allowing time for the base to be identified.
Photo by: Oxford Nanopore

Speed-Reading DNA Inches Closer

MIT Technology Review, February 26, 2009, by Katherine Bourzac — For DNA sequencing to become a routine part of patient care, it needs to become cheaper and faster. A company called Oxford Nanopore hopes to bring down both the cost and the time required for sequencing using a technique called nanopore sequencing. The company has now made an important demonstration of its technology: for the first time, researchers were able to identify DNA bases with near total accuracy. In addition to identifying the four bases of DNA, the technique can also detect a modified version of one of the bases, which may be responsible for causing cancer and other diseases.

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Speed reader: A DNA base (red) passes through a protein tunnel lined with a sugar (blue and green bubbles). The sugar slows down the DNA as it moves through the pore, allowing time for the base to be identified.
Credit: Oxford Nanopore

The new technique allows for the direct identification of bases without the fluorescent labels and imaging equipment used for conventional high-speed sequencing. Direct reading of DNA should not only be faster and cheaper, but it should also make it possible to perform more complex analysis, says Jeffrey Schloss, program director for technology development at the U.S. National Human Genome Research Institute. The Oxford Nanopore system’s ability to detect the DNA modifications catalogued by an emerging field called epigenetics is particularly exciting, says Schloss. For example, the addition of organic molecules called methyl groups to one of the bases has been shown to play a role in the development of diseases such as cancer. But it is arduous to detect these modifications using conventional sequencing methods, so the full effects and why they happen are still not well understood.

Oxford Nanopore researchers have not yet demonstrated that they can process complete DNA sequences using their system. However, the new results, published this week in Nature Nanotechnology, are an important proof of concept for nanopore sequencing. “They’ve shown the feasibility of all the steps,” says Schloss.

The system that the company used to identify DNA bases is a tunnel-like protein embedded in a membrane very similar to that which surrounds biological cells. The flow of ions across the membrane and through the pore creates a current that can be measured using an electrode similar to those used to study neurons in the lab. By applying a strong electrical potential across the membrane, researchers drive DNA bases through the pore. As each base passes through, it modifies the current flowing across the pore in a characteristic way.

The key to making the method work is controlling the flow of the bases through the protein pore. DNA bases are “too small to be identified on their own: they would fly through,” says James Clarke, a scientist at Oxford Nanopore. So a sugar molecule lining the opening bulks it up so that the DNA doesn’t zip through too rapidly. In previous versions of the nanopore system, this sugar molecule was rather loosely associated with the pore, moving in and out. Company researchers led by founder Hagan Bayley, who is also a professor of chemistry at the University of Oxford, made it possible to read DNA bases one after the other by chemically bonding the sugar to the inside of the nanopore.

Oxford Nanopore can identify bases, but not yet in sequence. The system that it has demonstrated involves passing chopped-up DNA, not whole strands, through the nanopore. The company is now working on a setup for feeding long strands of DNA through the pore one base at a time. To do this, the researchers must attach an enzyme called an exonuclease to the nanopore. They hope that bases will be chopped off one at a time by the enzyme and will pass through the pore to the other side.

“There’s some question [about] what will happen when you put long strands of DNA in front of the nanopore,” says Schloss. “Will it form a hopeless knot?”

This is just one of several unknowns confronting researchers. To make the technology truly scalable and commercially viable, the pores will need to be grouped in large arrays, and the company will need to develop a less complicated way of reading the electrical signals from the pores. Oxford Nanopore says that it is currently working on both of these problems.

A potential pitfall of Oxford’s nanopore-exonuclease approach, says Schloss, is that the DNA will be destroyed as it has been read, making it impossible to resequence a strand to check for errors.

However, there are other approaches to nanopore sequencing that are less destructive. David Deamer, emeritus professor of chemistry at the University of California, Santa Cruz, who first came up with the concept of nanopore sequencing in the 1990s and is a scientific advisor for Oxford Nanopore, points out that this is not the first demonstration of a nanopore system that can identify all DNA bases. Last year, researchers led by Reza Ghadiri at the Scripps Institute, in La Jolla, CA, sequenced a 10-base-long strand of DNA using another nanopore technique. The flow of DNA through the Scripps system, which is based on Deamer’s original concept, is controlled by an enzyme that acts as a ratchet, moving the molecule forward one base at a time. But this system is much too slow, advancing at a rate of one base every 10 minutes, and the Scripps researchers are working on speeding it up.

Oxford Nanopore hasn’t put all its eggs in one basket. It has licensed technology for several nanopore-sequencing methods, including Deamer’s and another that uses an artificial nanopore: a silicon wafer punched with nanoscale holes and lined with carbon nanotubes the conductance of which changes as the DNA passes.

“One of these approaches will have a breakthrough and will be able to sequence at a rate faster and cheaper than what we do now,” predicts Deamer. Neither the researchers at Oxford Nanopore nor those at competing labs are willing to speculate about just when this will happen, or what such a system would cost per genome. But Schloss says it’s possible that one of the groups will meet the National Human Genome Research Institute’s original target year of 2014 for successful nanopore sequencing.

Target Health contributes to the US Green Revolution by enabling clients to go paperless with its eClinical Trial software & tool kit, created in-house by an IT Department, second to none.

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Executive of the Year 2009 – T. Boone Pickens

Despite strong head winds, T. Boone Pickens tirelessly pushes plan to reduce America’s foreign oil dependence

Dallas Business Journal, by Chad Eric Watt — It’s just before 3 p.m. Central time, and T. Boone Pickens is tired.

The 80-year-old is on the final leg of a three-day trip spent promoting his plan to reduce American dependence on foreign oil.

In transit, and between speaking engagements (Oklahoma City, Washington, D.C., and Austin on this jaunt), Pickens has been checking with the traders running his two energy-focused hedge funds.

They’ve been struggling.

Energy prices are slumping. At 3 p.m. on Dec. 4, crude oil prices closed at $43.67 a barrel, down more than $3 on the day. Since their midyear peak, oil prices have fallen more than $100, costing Pickens about $2 billion.

A transformation of American energy policy, which seemed essential in the face of $4-a-gallon gasoline, has taken a back seat to the financial crisis, global recession and, on this particular day, the automakers’ financial bailout, which was still being hotly debated by Congress.

Aboard his Gulfstream G550 on the first cold day of December in Texas, Pickens is facing headwinds on all fronts, including a blue norther slowing progress between Austin and Dallas.

How do you know when to quit? When is it time to pull some chips off the table? Pickens doesn’t understand the questions. Past the age when most executives retire, he’s made more money for himself and investors than he did in a prodigious first 60 years.

But the last half of 2008 proved difficult for the oil tycoon turned energy activist. And it is largely because of the tenacious, against-all-odds fight he has launched for nothing less than America’s energy independence that T. Boone Pickens has been chosen as the Dallas Business Journal’s 2009 Executive of the Year.

In a nutshell, the Pickens Plan is an initiative to reduce U.S. dependence on foreign oil by 38% in the next 10 years. Pickens aims to accomplish that near-term goal by adding electricity-generating wind turbines in rural Plains states and connecting that power source to a national electricity grid.

Whether he ultimately wins or loses his quest to change U.S. energy consumption and production habits, Pickens’ impact on Texas, Dallas, the oil industry and universities from Houston to Stillwater, Okla., will be felt for generations to come.

At the moment, however, he has to focus.

In five hours, Pickens said while still airborne, he’ll be asleep. But first, a working dinner with the BP Capital staff.

The next day he’ll be up at 5 a.m. for exercise. Sleeping in tomorrow isn’t an option for T. Boone Pickens. He hasn’t gotten in his workout while he’s been on the road.

Similarly, changing his energy outlook, altering his hedge fund positions and toning down his energy dependence crusade are not options.

“He doesn’t drop anything. When he takes on anything else, his days just get longer,” said Bobby Stillwell, Pickens’ longtime attorney.

And when headwinds slow his progress, Boone doesn’t alter his course.

“That’s Boone at his best. He keeps going, under pressure, under distraction, he’ll keep going,” Stillwell said.

80 years, $3.1 billion and 1 plan

Despite the challenges he’s faced recently, Pickens accomplished much in 2008.

He celebrated his 80th birthday in May with a lavish bash at the Dallas Country Club thrown by his new wife, Madeleine, featuring entertainment from comedian Dennis Miller and singers Andrea Bocelli, Sarah Brightman and Katharine McFee.

He published his third memoir, “The First Billion is the Hardest,” and plans to donate profits from the book to programs supporting family members of wounded soldiers.

Apart from that project, Pickens and his foundation gave more than $118 million to charities, including Oklahoma State University, Big Brothers Big Sisters of North Texas and the Congressional Medal of Honor Foundation.

In addition to the DBJ recognition, Pickens was in the running for the Texan of the Year honor by The Dallas Morning News and Man of the Year by Time magazine, which went to Barack Obama. The DMN passed Pickens over, naming him No. 3. But the Texas Legislative Conference named him Texan of the Year in December.

Most importantly to Pickens, he’s made America’s dependence on foreign oil into a first-100-days priority for president-elect Obama.

The goal of the Pickens Plan is to generate 22% of U.S. electricity with wind. (Currently about 8% of electricity comes from all “green” options including wind, solar, water and other options.)

He would then take the natural gas that is currently being used to generate electricity and replace some gasoline as a transportation fuel. By Pickens’ math, that would amount to a 38% reduction in American reliance on foreign oil in the next decade.

Pickens has spent about $60 million of his own money advertising the plan, and countless hours of his own time in the last six months traveling to pitch the plan to practically any audience that fits his schedule.

At the same time, Pickens has ordered $2 billion worth of wind turbines to build what he said will be the largest wind farm in the world in the Panhandle town of Pampa, although plans for the project were put on hold last fall when his wind power company couldn’t find financing to buy the 667 General Electric turbines.

Despite that setback, his message still resonates.

“If it were not for Boone spending that money and engaging both parties in the debate, it would’ve been shoved under the carpet no matter who won,” said Ken Luce, California and Southwest region president for the public affairs firm Weber Shandwick and a former campaign strategist for Texas Gov. Rick Perry and others.

Pickens, a conservative through-and- through, has made inroads into the new Democratic regime, and it appears he’s being taken seriously.

He’s made his pitch to Carol Browner, Obama’s future energy czar, and North Dakota Sen. Byron Dorgan has pledged to introduce wind-power aspects from Pickens’ plan to the next Congress.

Pickens and California Democrat Sen. Nancy Pelosi, who as speaker of the House is the highest-ranking lawmaker in Congress, have collaborated to push for parts of the Pickens Plan.

Similar to the Obama campaign, Luce said, Pickens has built a database of supporters outside of Washington, D.C. Those backers are looking to take action, and should Washington attempt to put energy dependence back on the shelf, those backers will be ready to cry foul.

Pickens is confident that backers and reporters will make sure the issue will be on Obama’s short list.

“I think Obama, he’s got himself in a spot when he says no imports of Mideast oil in 10 years. I’ve stirred up the pot to the point where journalists will ask, ‘How’re we coming on that, Mr. President?’ ” Pickens said.

If Obama doesn’t reduce America’s dependence on foreign oil, then soon, Pickens said, “We’ll have to go in and take it.

“There’s no way this country can be secure importing 70% of its oil and half of that coming from the Mideast and Africa. We’re insane to do that,” he said. “We’re paying for both sides of the war. There’s no question about that.”

That grim assessment underscores the importance Pickens puts on his plan to replace a portion of transportation fuels with natural gas and replace natural gas electricity generation with wind power.

The Pickens gospel

But it’s a small part of the gospel he’s been preaching since July 8, the day Pickens unveiled his energy plan.

The Pickens Plan message is more focused on blue skies, whirling turbines and American empowerment. He’s been barnstorming the nation like a jet-powered revival preacher offering hope and jobs in a time of despair and cutbacks.

Like the revival preacher, Pickens can look you in the eye and say he’s not concerned about profits.

“At 80 years old, I don’t think you go out and put $50 (million) or $60 million in something trying to figure out how you’ll make money on it. It isn’t realistic,” Pickens said. “As far as the wind goes, gosh there’s a front-row seat for everybody. There’s so much wind between Texas and Canada.”

Every month since July, Pickens and his Pickens Plan entourage have spent about two out of every three days in the air delivering the plan in town hall and briefing-room settings.

At the same time, he’s been touting his book, which is half memoir and half advocacy piece for the Pickens Plan.

When he launches into his well-practiced whiteboard presentation on the Pickens Plan, it’s easy to forget that he’s 80 years old. Talking rapidly, his mouth is trying to keep up with his brain, and his right hand is racing to keep up with his words.

On stage, Pickens is slim and spry, he moves quick and deliberately, his brain always one step ahead. Up close, he shows some evidence of his actual years. His skin hangs a little loose and his face is etched with the striations that come from decades under Oklahoma and Texas suns. His hearing is weak.

Those signs of age are more clear between presentations and calls back to the office. As the year winds to a close, the tireless campaigner was looking a little tired.

Back to the airwaves

The Monday before his tiring December trek, Pickens kicked off the week in his office, shooting a commercial that’s set to hit the airwaves in January after president-elect Obama’s inauguration.

He had spent the prior Saturday watching his beloved Oklahoma State Cowboys football team lose an intense shootout to the Oklahoma Sooners.

That Monday, Pickens hit the office with the same kind of energy that filled Boone Pickens Stadium for the game. He launched into his script with a practiced delivery and a forceful Okie-Tex baritone.

“Goddamn, I’ve lived through 14 presidents!” he remarked as he read aloud the script.

Pickens got his workout in early this morning (lunges and squats with a 40-pound vest), and he’s practically playful. As the commercial crew that’s commandeered his conference room sets up, he peppers inside jokes into the script: “I’m back again, and now I got a little money back,” referring to a late fall rally in energy prices, which helped him regain some lost ground in his hedge funds.

As he wraps up the commercial shoot, Pickens chats with members of his campaign brain trust on energy policy.

“How many people now have a plan?” he asked. “Everybody has a plan now, is that coming off of me?” (Of course, the group he’s paying to push the plan says yes.)

Before waiting for an answer, Pickens is out of his makeup and visiting with a BP Capital trader to check on the markets — particularly oil prices and energy equities.

Their discussions are quick and decisive, and Boone moves on to someone else.

The office of BP Capital, on the second floor of a Preston Center office tower, is a comfortable beehive of activity. It’s finished with wood and leather chairs accented by Pickens’ personal and political mementos as well as large-scale hydrology, wind and geology maps. About 35 people work there, although it feels like twice that many. This is the place where Pickens looks most comfortable, most energized and most focused. His employees are loyal, happy to see him and work with him.

When attorney Stillwell retired from the Houston office of the Baker Botts law firm in 2001, Pickens talked to him about doing some work in-house in Dallas.

“We’re seven years into that program,” Stillwell said. “I didn’t ever get to work at 7 when I was at Baker Botts, but I do now.”

Hometown crowd

The Pickens Plan campaign has kept Boone away from the office more and more as he pushes toward the start of a new administration. So when the Borders bookstore at Preston Road and Royal Lane in Dallas hosted a book signing and talk by Pickens, his own employees mingled with plan fans and charity recipients — ranging from the Center for BrainHealth at the University of Texas at Dallas to the Dallas Junior League.

That late November day was an easy travel day for Pickens. Only Fort Worth and Dallas were on his itinerary.

Dallas businessman Fury Zaidi brought a white, natural gas-powered, convertible stretch Oldsmobile festooned with longhorns on the hood and pro-Pickens signs elsewhere to the signing.

The weird rolling billboard isn’t the kind of thing Pickens and his strategists would put together, but that’s the way grass-roots movements grow.

In addition to $60 million and counting on televisions spots, the Pickens Plan has included an active weblog and vigorous use of interactive Web 2.0 community tools such as Facebook and Twitter.

All told, the Pickens Plan counts 1.3 million supporters in cyberspace.

Zaidi, who runs a Beckley Avenue business converting gasoline vehicles to natural gas, has a stake in seeing the Pickens Plan put into action. But he’s also got questions for Pickens.

Pickens is a founder of Clean Energy Fuels Corp., the main operator of natural gas fuel stations in Dallas. So why, Zaidi wonders, is natural gas fuel so much more expensive in Dallas than it is on the West Coast?

Half an hour before Pickens’ arrival, Pickens’ fans had filled all the chairs set up for his talk, sitting quietly and reading copies of “The First Billion.”

The mostly male and middle-aged fans at the Preston Hollow event were sitting so politely that they didn’t even seem to notice Pickens and his entourage sweep in and conduct a talk radio interview and pose for pictures with gracious Junior Leaguers before he took the podium and delivered his familiar speech.

Less than a mile from his Preston Hollow estate, Pickens was at home and in his element. Surrounded by enthusiastic supporters, he stayed well past his required time to sign books and speak with fans. By the event’s end, more than 300 people left with one or more signed copies of his book.

Connecting with Dallas

Dallas has been a good fit for the oilman who left Amarillo for Dallas in 1990 and still has little good to say about the town where he built Mesa Petroleum into his first fortune.

In his newest memoir, Pickens notes that he even moved his parents’ remains from Amarillo to a cemetery in Holdenville, Okla., his birthplace. “I now had no reason to ever return to Amarillo. I felt I had overstayed in a small town,” he writes.

The people of Amarillo have mixed feelings about Pickens.

“With Boone Pickens, I’ve never heard the same story twice,” said Les Simpson, now the publisher of the Amarillo Globe-News. (Simpson arrived after Pickens’ Amarillo era, in which he famously feuded with the hometown newspaper.)

“With business success came business ego, and he wielded a big stick,” Simpson said. “He burned many a bridge when he left town.”

But people who worked for Pickens remember him fondly, said Jerry Hodge, chairman of Maxor Pharmaceuticals, which now occupies the 10-story building that was Mesa’s headquarters.

“We’ve got people who work for Maxor who used to work for Mesa who speak very highly of him,” Hodge said.

Hodge himself is in the midst of reading Pickens’ latest book and is ready to take one piece of advice.

“I’m getting ready to start working out,” said Hodge, 66.

Pickens connected with Dallas for several reasons. He writes: “Not only has the city accepted me with open arms, but I also soon realized the business significance of being headquartered in one of the country’s major metropolitan areas.”

In contrast to his Dallas bookstore pep rally, giving the same pitch in Austin to 23 freshman state legislators and University of Texas staffers in the shadow of the Darrell K. Royal-Texas Memorial Stadium some two weeks later, Pickens appeared less at home.

The new state House members, all elected 30 days before, were a bit like deer in Austin’s city headlights, trying to find their bearings around the capital and big political issues as Pickens launched into his whiteboard presentation chock-full of numbers.

“What about oil industry jobs? Wouldn’t the Pickens Plan threaten jobs in my district?” asked a young Houston legislator.

Pickens replied that his plan was about creating jobs, and reducing dependence on foreign oil. Like the book signing, Pickens lingered, speaking directly with newly minted state reps, including the gentlemen concerned about jobs there.

It’s important to Pickens to connect and talk to everyone who wants to speak with him.

“Even if you don’t have 10 minutes, you’ve got to take that 10 minutes,” he said, adding that he felt he was able to get the concerned congressman to come around.

Then he turned to a cell phone to resume the ongoing discussion with his hedge fund traders. The day wasn’t going well.

A pause on the upward climb

As energy prices last fall continued to follow the downward path of economic output and consumption, Pickens remained confident that the setback was temporary, even if temporarily costly.

When he kicked off the Pickens Plan, gasoline cost an average of $4.11 a gallon. At that rate, Pickens had pegged American spending on foreign oil at $700 billion a year — long before $700 billion became more associated with the government’s financial system bailout.

“That’s $700 billion at $140 a barrel,” Pickens said. “The dollar amount will vary with price, but the quantity just keeps going up.”

At current crude oil prices, that dollar figure would stand between $200 billion and $250 billion. But again, current energy prices are temporarily low, Pickens said. We’ll see $100 barrels of oil return very soon, he insists.

Underpinning that outlook is a firm belief in the peak oil theory — the concept that global oil production has already peaked and has begun to decline.

It’s a theory that major oil firms and petro-producing nations generally don’t ascribe to.

“The major oil company guys say it hasn’t peaked. I say ‘Why don’t you increase your production?’ ” Pickens said. “They don’t increase their production. The best they can do is flatline. Global supply is also on the same spot — 85 million barrels a day is all the world can do.”

A California trouncing

While the Pickens Plan has kept some of its momentum on the national stage, it was dealt a serious trouncing in California on November Election Day.

A proposition to use California funds to shift large fleet vehicles from diesel and gasoline to natural gas was defeated 59.5% to 40.5%.

One key factor in that was an active opposition that portrayed Pickens as a backer of the proposition standing to reap a windfall on the backs of California taxpayers, said Richard Holober of the Consumer Federation of California, one of the measure’s key opponents.

“Even after he spent $60 million nationally, our polling indicated few people had a favorable opinion of Pickens,” Holober said.

Luce, the Weber Shandwick PR specialist, said the California proposition actually got swept up in the sudden seizure of credit markets and California’s real estate collapse.

“It got caught in everything else, including the gay marriage initiative,” he said. “I believe there were bigger issues than just that.”

Still, Holober pointed out, several larger spending propositions did receive funding.

Even when things don’t go according to plan, Pickens can interpolate some value to his work.

“When we started on July 8, gasoline was (at an average of) $4.11 (a gallon); now it’s less than half that, so I did something,” Pickens said, straight-faced.

But at the same time, the decline in energy prices has caused him to put his plans for a giant Panhandle wind farm near the town of Pampa on hold. When natural gas prices go down, the economics of power generation by wind disappear. But the challenge for that project was getting access to financing.

While Pickens isn’t happy about delaying the wind project, he said lower-priced natural gas is good for the country.

“It’s sort of like seeing your mother-in-law go off the side of the mountain in your new Cadillac,” he quipped. “You have mixed feelings about it.”

Little time for reflection

There’s little that T. Boone Pickens has mixed feelings about. Practically every move he makes is done with certainty, attorney Stillwell notes.

“Once Boone decides he’s going to do a big project like that, No. 1, you know he’s been thinking about it a long time and, No. 2, you can only help him refine it and improve it,” he said. “You don’t know for sure when you start what the finish is, or at what point you declare victory.”

For commercial ventures, you know you’re finished when it starts making money. “With the Pickens Plan, that’s a patriotic personal fulfillment kind of thing,” Stillwell said.

“He already knows he’s gotten it into the national mix, and he knows (the Obama) administration transition team and Congress are supportive of part of it.”

On the flight back from Austin where he met with new lawmakers, Pickens is preoccupied by energy prices and the crisis du jour — a potential bailout for the Big Three U.S. automakers. Highlights of the day’s congressional testimony on that topic are running on his plane’s ticker television.

The prospect of an auto bailout disgusts Pickens, the former corporate raider/shareholder activist: “They divvied up the equity between management and the workers. Equity owners had nothing left,” he said.

A few minutes and a mini-catnap later, Pickens is back on the tarmac at Love Field, heading for his car.

“I’m going to work,” he declares to everyone.

It’s no surprise to his entourage. Despite the headwinds, literally and figuratively, it’s what he does. He never stops.

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Does this look like the traditional face of an environmentalist? Take a look at this interview with T. Boone Pickens about why he is investing in Wind Power in West Texas:

Investing in Wind

The concept of viewing our dependence on foreign oil as a historically massive transfer of wealth is excellent. It allows people on every side of the energy debate to frame it in a way that shows what is critically important about our dependence on oil.

I am a fan of locally produced energy. Even when we mine and burn coal, at least as a country we see the impact on our soil. Divorcing ourselves from our consumption (and consumption of anything, not just oil) is one of the first mistakes we need to rectify, and in a hurry.
I am a firm believer that once you frame consumption, reduction becomes a set of quantifiable goals. If you don’t have that frame, you have no place to start.

Now I am not naive enough to think that a lifelong oil guy like T. Boone Pickens is doing this out of the goodness of his heart. Like all of us he has larger motives – in his case mainly profit motives. In fact I would put money on the fact that this story is way more complicated than it seems.

Pickens has been taking advantage the odd regulations regarding drilling in Texas and is buying up land above a set of aquifers. So along with lobbying himself into a Water Authority and distributing water into the Dallas metropolitan area, I have no doubt that wind generated electricity can be easily transmitted down those same pipe lanes.

Eminent Domain is a wonderful concept.

If it turns out that there is Natural Gas on his land, then you can see the whole plan come together – one $2 billion pipeline, three critical services.
There is big money in this thing for Pickens, and all in all it is pretty brilliant if totally shady.

But in the end, I sit here and ask myself; “Do I Care?” And the answer is no. From the outset of embarking on this journey, I told myself that I didn’t care why people came to the table as long as they came. Well Pickens, came to the table because he saw huge money in wind power. I may not personally love all of his reasons, but his reasons frame the problems in ways many other people can identify with. And for that I am excited to welcome an old Oil Wildcatter to the party.

Let’s talk more about the transfer of wealth, it is a great point and one that I never would have conceived of if not for Pickens’ approach. It is simple and straight forward, and it matters.
Here is the You Tube explanation of the plan.

Here is the full website: www.pickensplan.com

Judge for yourself.

NYT, 02/23/09 — Researchers have engineered antibodies that attack a part of the influenza virus that is shared by many strains.

Flu Vaccines go after the spikes on flu viruses, preventing them from penetrating human cells and injecting viral RNA. But there are 16 types of spikes, and the shapes mutate constantly. So flu vaccines have to be reformulated each year.

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New Antibodies go after the neck of the spike, which apparently does not mutate. Once clamped, the neck can still penetrate a cell, but it cannot inject RNA. Mice tested with the antibodies were protected from H5N1 flu in 80 percent of cases.
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Source: Nature Structural & Molecular Biology

The New York Times, February 24, 2009, by Benedict Carey — For years, psychiatrists have known that children who are abused or neglected run a high risk of developing mental problems later in life, from anxiety and depression to substance abuse and suicide.

The connection is not surprising, but it raises a crucial scientific question: Does the abuse cause biological changes that may increase the risk for these problems?

Over the past decade or so, researchers at McGill University in Montreal, led by Michael Meaney, have shown that affectionate mothering alters the expression of genes in animals, allowing them to dampen their physiological response to stress. These biological buffers are then passed on to the next generation: rodents and nonhuman primates biologically primed to handle stress tend to be more nurturing to their own offspring, Dr. Meaney and other researchers have found.

Now, for the first time, they have direct evidence that the same system is at work in humans. In a study of people who committed suicide published Sunday in the journal Nature Neuroscience, researchers in Montreal report that people who were abused or neglected as children showed genetic alterations that likely made them more biologically sensitive to stress.

The findings help clarify the biology behind the wounds of a difficult childhood and hint at what constitutes resilience in those able to shake off such wounds.

The study “extends the animal work on the regulation of stress to humans in a dramatic way,” Jaak Panksepp, an adjunct professor at Washington State University who was not involved in the research, wrote in an e-mail message.

He added that the study “suggests pathways that have promoted the psychic pain that makes life intolerable,” and continued, “It’s a wonderful example of how the study of animal models of emotional resilience can lead the way to understanding human vicissitudes.”

In the study, scientists at McGill and the Singapore Institute for Clinical Sciences compared the brains of 12 people who had committed suicide and who had had difficult childhoods with 12 people who had committed suicide and who had not suffered abuse or neglect as children.

The scientists determined the nature of the subjects’ upbringing by doing extensive interviews with next of kin, as well as investigating medical records. The brains are preserved at Douglas Hospital in Montreal as part of the Quebec Suicide Brain Bank, a program founded by McGill researchers to promote suicide studies that receives brain donations from around the province.

When people are under stress, the hormone cortisol circulates widely, putting the body on high alert. One way the brain reduces this physical anxiety is to make receptors on brain cells that help clear the cortisol, inhibiting the distress and protecting neurons from extended exposure to the hormone, which can be damaging.

The researchers found that the genes that code for these receptors were about 40 percent less active in people who had been abused as children than in those who had not. The scientists found the same striking differences between the abused group and the brains of 12 control subjects, who had not been abused and who died from causes other than suicide. “It is good evidence that the same systems are at work in humans that we have seen in other animals,” said Patrick McGowan, a postdoctoral fellow in Dr. Meaney’s lab at McGill and the lead author of the study.

His co-authors, along with Dr. Meaney, were Aya Sasaki, Ana C. D’Alessio, Sergiy Dymov, Benoît Labonté and Moshe Szyf, all of McGill, and Dr. Gustavo Turecki, a McGill researcher who leads the Brain Bank.

Because of individual differences in the genetic machinery that regulates stress response, experts say, many people manage their distress despite awful childhoods. Others may find solace in other people, which helps them regulate the inevitable pain of living a full life.

“The bottom line is that this is a terrific line of work, but there is a very long way to go either to understand the effects of early experience or the causes of mental disorders,” Dr. Steven Hyman, a professor of neurobiology at Harvard, wrote in an e-mail message.

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Studies Try to Tease Apart the Links Between Depression and Heart Disease

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The New York Times, by Nicholas Bakalar — People who are depressed are literally sick at heart: they have a significantly increased risk for cardiovascular disease, and no one knows exactly why. Now three new studies have tried to explain this, and they arrive at subtly different conclusions.

The first, led by Dr. Mary A. Whooley of the Veterans Affairs Medical Center in San Francisco, studied 1,017 patients with coronary artery disease for an average of more than four years. Although the study found an association of depression with heart disease, when researchers statistically corrected for other medical conditions, disease severity and physical inactivity, the association disappeared.

They concluded with a relatively straightforward explanation: depression leads to physical inactivity, and lack of exercise increases the risk for heart disease. The study appears in the Nov. 26, 2008 issue of The Journal of the American Medical Association.

A second study, published in The Journal of the American College of Cardiology, provides a different perspective. It included more than 6,500 healthy men and women with an average age of 51. Researchers tested them for depressive symptoms and followed them for an average of more than seven years.

This study, too, found that behavioral issues like smoking and inactivity were the strongest factors in the increased risk for heart disease among people who are depressed or anxious, accounting for 65 percent of the difference in risk. But they also found that depressed people had higher rates of hypertension and higher levels of C-reactive protein, and that these two physiological factors together accounted for about 19 percent of the increased risk. Mark Hamer, a senior researcher at University College London, was the lead author.

While these two studies suggest that the mechanism by which depression exerts its effect is mostly or entirely through poor health behaviors, a third study, in the December 2008 issue of The Archives of General Psychiatry, found that something else might be even more important.

This paper, whose senior author was Dr. Brenda Penninx, a professor of psychiatry at VU University in Amsterdam, studied 2,088 well-functioning adults ages 70 to 79. It found no difference in physical activity between those who were depressed and those who were not.

But it did find that depressive symptoms were associated with an increase in visceral fat accumulation — the pot belly that is a known risk factor for cardiovascular illness. This suggests that there is a biological mechanism that links depression with physiological changes independent of how much a person exercises.

To further complicate matters, Dr. Penninx suggested that her physically healthy subjects might have a different kind of depression. “There is now quite a lot of evidence that among heart attack patients, the physical symptoms of depression are more prevalent,” she said, “which suggests that their depression is different from that seen in an otherwise healthy sample.”

For now, Dr. Hamer, of London, offered what might be the last word on the complicated relationship between depression and heart disease.

“It’s really quite difficult to understand,” he said.

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Depression Diversity: Brain Studies Reveal Big Differences Among Individuals

Scans show depressed people have fewer serotonin and opioid receptors, and that variation is linked to symptoms and treatment response

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On the left, the colorful areas show where serotonin receptor levels were much lower in people with severe depression

ANN ARBOR, Mich, U-M Medical School, by Kara Gavin – Depressed people may have far fewer of the receptors for some of the brain’s “feel good” stress-response chemicals than non-depressed people, new University of Michigan Depression Center research shows.

And even among depressed people, the numbers of these receptors can vary greatly. What’s more, the number of receptors a depressed person has appears to be linked with the severity of their symptoms — and the chances that they’ll feel better after taking a medication.

These preliminary findings, presented Tuesday at the American Psychiatric Association’s annual meeting in Washington, D.C., amplify a growing understanding of depression as a condition that affects different people in different ways. The new data, and other researchers’ findings, are showing that depression is solidly rooted in genetic and molecular factors that are unique to each individual.

The lead U-M researcher, Jon-Kar Zubieta, M.D., Ph.D., says these new results bolster what other researchers have been finding in recent years.

“There’s a substantial amount of biological difference even among people who have major depression, which is just as important as the biological differences between people with depression and people without,” he says. “The more we can understand about these differences, the better we can address treatment to the individual and have the greatest effect on symptoms.”

At the APA meeting, Zubieta presented data from positron emission tomography, or PET, scans of the brains of patients who met the criteria for major depression but had not yet received treatment for it. Those scans were compared with scans of the brains of non-depressed comparison volunteers.

In one group of depressed and non-depressed volunteers, the scans were made using a tracer that can reveal the location and concentration of a particular type of receptor. Called the 5HT1a receptor, it allows brain cells to receive signals from serotonin, a chemical neurotransmitter produced by the brain.

Serotonin levels in the brain are linked to depression, but the importance of 5HT1a receptor concentrations in the brains of depressed people has been cloudy. That’s why Zubieta’s team chose to scan only people who had not yet received antidepressant medications, since some such medications may actually encourage the brain’s cells to make more serotonin receptors – and mask the actual level of receptors that the person has naturally.

In the study, 5HT1a receptor concentrations were markedly lower in depressed people compared with non-depressed people, in both the left and right hippocampus regions of the brain.

But even among depressed people, the lower a person’s 5HT1 receptor levels were, the worse he or she scored on assessments of the ability to function day to day – and the less likely he or she was to get relief from symptoms when the researchers prescribed a common antidepressant.

This finding of individual variation may help explain why in current depression treatment, some patients find great relief from a medication that doesn’t help other equally depressed patients, says Zubieta, who is the Phil F. Jenkins Research Professor of Depression in the U-M Department of Psychiatry. He also holds positions in the U-M Nuclear Medicine division, and the Molecular & Behavioral Neuroscience Institute.

The other group of volunteers – both depressed and non-depressed — received PET scans with a tracer that allowed the researchers to see the mu-opioid receptors in their brains. These receptors are the gateway for signals sent by chemicals called endogenous opioids — the brain’s natural “painkillers” – which are involved in stress response, including response to pain.

Another name for the neurotransmitters that bind to mu-opioid receptors is endorphins, which have become known as a “feel good” chemical involved in reinforcing rewarding experiences. Illicit drugs such as heroin also act upon mu-opioid receptors, creating the “high” sensation and probably playing a role in the addiction process.

In this group of depressed and non-depressed volunteers, the researchers studied the distribution of the mu-opioid receptors and looked at how active the receptors were when the volunteers were asked to summon a sad memory or scenario to mind.

Depressed volunteers had lower concentrations of mu-opioid receptors to begin with. But when they underwent the “sadness challenge,” those receptors were much more active than the receptors in non-depressed people. And, just as with the serotonin 5HT1a receptors, the fewer mu-opioid receptors a person had, the less well he or she responded to an antidepressant medication.

Zubieta and his colleagues are now working to submit these new data for publication. At the same time, they are continuing to recruit depressed volunteers who are not taking medication for more brain-imaging studies. To find out more about how to participate in depression research at the U-M Depression Center, visit www.umengage.org.

For more on research by Zubieta and other researchers at the U-M Depression Center, visit www.depressioncenter.org.

The study was funded by the National Institutes of Health, by the Pritzker Foundation and by NARSAD, a leading mental health charity.

ScienceDaily.com — The brains of individuals with major depressive disorder appear to react more strongly when anticipating pain and also display altered functioning of the neural network that modifies pain sensitivity, according to a new report.

“Chronic pain and depression are common and often overlapping syndromes,” the authors write as background information in the article. Recurring or chronic pain occurs in more than 75 percent of patients with depression, and between 30 percent and 60 percent of patients with chronic pain report symptoms of depression “Understanding the neurobiological basis of this relationship is important because the presence of comorbid pain contributes significantly to poorer outcomes and increased cost of treatment in major depressive disorder.”

Irina A. Strigo, Ph.D., of the University of California San Diego, La Jolla, and colleagues studied 15 young adults with major depressive disorder (average age 24.5) who were not taking medication and 15 individuals who were the same age (average 24.3 years) and had the same education level but did not have depression. Patients with depression completed a questionnaire that evaluated their tendencies to magnify, ruminate over or feel helpless in the face of pain. All participants underwent functional magnetic resonance imaging (fMRI) while their arms were exposed to a thermal device heated to painful levels (an average of 46.4 degrees to 46.9 degrees Celsius, or about 115 degrees to 116 degrees Fahrenheit) and also to non-painful temperatures. Visual cues (a green shape for non-painful warmth and a red shape for painful warmth) were presented before the heat was applied.

Compared with the controls, patients with depression showed increased activation in certain areas of their brain—including the right amygdala—during the anticipation of painful stimuli. They also displayed increased activation in the right amygdala and decreased activation in other areas, including those responsible for pain modulation (adjusting sensitivity to pain), during the painful experience.

To examine whether the activation of the amygdala was associated with passive coping styles, the researchers compared the percentage change in the activations of the amygdala with the helplessness, rumination and ramification reported by the participants with depression. “Significant positive correlations were observed in the major depressive disorder group between greater helplessness scores and greater activity in the right amygdala during the anticipation of pain,” the authors write.

“The anticipatory brain response may indicate hypervigilance to impending threat, which may lead to increased helplessness and maladaptative modulation during the experience of heat pain,” the authors write. “This mechanism could in part explain the high comorbidity of pain and depression when these conditions become chronic.”

“Future studies that directly examine whether maladaptive response to pain in major depressive disorder is due to emotional allodynia [a pain response to a non-painful stimulus], maladaptive control responses, lack of resilience and/or ineffectual recruitment of positive energy resources will further our understanding of pain-depression comorbidity,” they conclude.

This study was supported by Barrow Neurological Foundation, grants from the National Institute of Mental Health, the National Association for Research in Schizophrenia and Depression and the University of California San Diego Center of Excellence for Stress and Mental Health.

Journal reference:

1. Irina A. Strigo, PhD; Alan N. Simmons, PhD; Scott C. Matthews, MD; Arthur D. (Bud) Craig, PhD; Martin P. Paulus, MD. Association of Major Depressive Disorder With Altered Functional Brain Response During Anticipation and Processing of Heat Pain. Arch Gen Psychiatry, 2008;65(11):1275-1284

Adapted from materials provided by JAMA and Archives Journals.

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The Conflict Of Reward In Depression

Stanford University Psychology Department — In Love and Death, Woody Allen wrote: “To love is to suffer…To be happy is to love. To be happy, then, is to suffer.” The paradoxical merging of happiness and suffering can be a feature of depression. A new study of regional brain activity using functional magnetic resonance imaging may help further our understanding of how happiness and suffering are related in depression.

Stanford University researchers recruited both depressed and non-depressed volunteers to undergo brain scans, via functional magnetic resonance imaging (fMRI), while they participated in an activity where they won and lost money. Dr. Brian Knutson, first author on this article, explains their findings: “When they anticipated winning money, both depressed and nondepressed individuals showed neural activation in the nucleus accumbens, a region implicated in the anticipation of reward. Only the depressed participants, however, additionally showed increased activation in the anterior cingulate, a region of the brain that has been implicated in conflict.”

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, notes that this finding indicates that “this complex mixture of findings suggests that depression is not simply the absence of reward, but rather a contamination of neural processing of rewards with features of neural processing of punishments.” Dr. Knutson agrees, commenting that “these findings are consistent with formulations that depression involves difficulties in the processing of positive information, and suggest more specifically that depressed people actually experience conflict when they are faced with the likelihood of receiving a reward.”

Dr. Krystal concludes that “one intriguing potential implication of this work is that some forms of depression may be experienced, not as the absence of pleasure, but as the ubiquitous presence of emotional pain, disappointment, or frustration.” Dr. Knutson and his colleagues are currently examining whether this increased experience of conflict when anticipating reward hinders recovery from depression.

The article is “Neural Responses to Monetary Incentives in Major Depression” by Brian Knutson, Jamil P. Bhanji, Rebecca E. Cooney, Lauren Y. Atlas and Ian H. Gotlib. The authors are affiliated with the Department of Psychology at Stanford University in Stanford, California. The article appears in Biological Psychiatry, Volume 63, Issue 7 (April 1, 2008), published by Elsevier.

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