(En)lighten up: The biology of depression

The sad thing about depression (besides the fact that is is depressing), is most people (even people with clinical depression) don't give a damn about this particular disease, until someone like Robin Williams takes the fast and horrible way out. 

We will mourn the loss of an influential person, a great artist like Williams, and then tune into our next flavor of the day, and the hands of time keep spinning while the list of quiet casualties (i.e., the not famous, living their lives of quiet desperation - thank you, Mr. Thoreau) keeps rising. And by casualties, I don't necessarily mean suicides. For people who have struggled with a major bout of depression, it can be a pretty serious wound by itself, with plenty of side effects. 

Taking the "lighten the hell up" approach doesn't usually work. But this isn't about eliciting cheap and temporary sympathy for these folks (most of whom lead the most ordinary of lives, content the great majority of the time). It's about awareness, and understanding a widespread issue (and maybe supporting whatever measures and efforts there are to reduce the bad shit). 

Since the news broke about Williams' suicide, the responses have run the gamut from one extreme to another, from criticism that he took the coward's way out, to the deepest sympathy. Personally, having faced the D-demon myself, I fall into the latter category. I certainly can't empathize with a person who was as globally beloved as Robin Williams, but can definitely understand the problem of facing the dark defenseless and hopeless. 

Depression is a complex thing. It isn't a case of the blues, not just that. Nor is it exactly like addiction, as some cyber-therapists have alleged -- admit you have a problem and deal with it, damn it ... go to a 12-step program! The thing is, as with most disease, of course you have to admit a problem and deal with it, otherwise, the disease generally wins. Like with cancer or diabetes or so many other things. 

With that in mind -- the squishy nexus of biology and depression -- here's a link that might help you better understand the biology behind depression: http://well.wvu.edu/articles/the_biology_of_depression

There's also this: http://www.allaboutdepression.com/cau_02.html

This also is really interesting: http://www.yalescientific.org/2011/02/uncovering-the-biology-of-depression/


Some of what we know is, at least 15 million adults in the U.S. suffer from a major depressive disorder in a given year; people with depression are four times as likely to develop a heart attack than those without a history of the illness (and after a heart attack, they are at a significantly increased risk of death or second heart attack); there is a high prevalence of depression that co-occurs with other illnesses (cancer, AIDS, Parkinson's); major depressive disorder is the leading cause of disability in the U.S. for ages 15-44 (and the leading cause of disability worldwide among persons five and older -- FIVE!!??); depression ranks among the top three workplace issues, following only family crisis and stress (which often lead to depression ... such a vicious cycle); its annual toll on U.S. businesses amounts to about $70 billion in medical expenditures, lost productivity and other costs; oh, and there are more than 30,000 suicides in the U.S. each year, at least two thirds of them caused by major depression (Robin Williams, hello!). 

The good news is, about 80 percent of those treated for depression show an improvement in their symptoms generally within four to six weeks of beginning medication, psychotherapy, attending support groups or a combination of these; but here's the thing: Despite its high treatment success rate, nearly two out of three people suffering with depression do not actively seek nor receive proper treatment and an estimated 50% of unsuccessful treatment, or non-treatment for depression is due to medical non-compliance (including financial factors). 

Meanwhile, smart people are working on the problem. Here's something about research that Georgia Tech is involved in:  http://news.emory.edu/stories/2014/04/precise_brain_mapping_improves_response_to_dbs/


The bottom line is, most folks haven't read this far because, quite honestly, depression isn't sexy (as opposed to liver disease and ribosomes and molecular biology and the other sexy stuff you're used to reading on this blog). Most folks just don't care, and they won't, until someone like Robin Williams takes himself out (to wit, this blog entry), and even then, most folks  are typically wired to a 24-hour news cycle, in which today's celebrity suicide gives way to tomorrow's new shiny thing. 

Good luck out there, be kind to each other. The world will keep spinning either way, at least for another four billion years or so. How it spins and how nice the ride is for the humans tethered to the big blue ball depends on the lot of us.


P.S. Here's a blog post by yours truly, of a more personal (and hopefully helpful) nature: http://fourcrickets.wordpress.com/2014/08/13/this-one-got-to-me/

Holy Grail: Getting closer to an HIV cure

This is the one. This is the project that Phil Santangelo will be talking about when he’s 80 and retired and rocking on the front porch, in some distant future – a promising, healthier future for mankind because, well, this is the one.

Santangelo, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology, is helping lead a research team that was recently awarded a $5.5 million grant from the NIH/NIAID (National Institute of Allergy and Infectious Diseases) for their role in a national, multipronged effort to once and for all cure HIV/AIDS.

“This is like the Holy Grail for a molecular imaging person who’s interested in infectious disease. From my point of view, this is it, this is huge,” says Santangelo, who is partnering with Emory’s Francois Villinger as principal investigators on the research, supported by the aforementioned R01 (which is the original and historically oldest grant mechanism used by the National Institutes of Health, or NIH).

The prospect of eliminating HIV from infected patients may be achievable with novel anti-retroviral therapies, but it would require new tools with greater sensitivity than what is now available. So the research aims to create and improve imaging technology to better monitor HIV reservoirs, the thought being that if you attack these elusive reservoirs, you can stop HIV. Santangelo says a finish line is in sight. Almost.

Here's the dilemma. A person who's infected with the HIV virus is treated with anti-retroviral drugs. They appear to work. Within a month, the virus is undetectable in the blood stream. It's been suppressed. But if you take the patient off the drugs, the virus comes back. It rebounds. "The drugs work but they are not sufficient to clear the virus. And really, we don't know why that is yet," Santangelo says. "Where is the virus? Where are the active reservoirs during suppression?"

The prospect of eliminating HIV from infected patients could be close at hand, but such a lofty goal will require new tools with greater sensitivity than currently available to monitor the progress of novel anti-retroviral therapies – not only in blood but also in organs that harbor such reservoirs and sites of residual viral replication in vivo.

“We’re not necessarily in this project, quote, creating the cure. But we’re creating a tool that’s going to give us a lot more information about how you might go about doing that,” Santangelo says. “Otherwise, it’s a shot in the dark, you’re just trying different approaches.  It’s trial and error. In the drug development world, trial and error is useful, but not ideal, and certainly not efficient”

This research and resulting improvements in imaging technology, he says, will eventually give drug developers more information than they’ve had before, about how drugs are affecting very specific parts of the body.

“It’s about giving them much more powerful information about what’s happening, as opposed to downstream information,” says Santangelo, whose research areas include molecular imaging, nano-biophotonics, and optical microscopy. The long-term aim is to cure HIV, he adds, “and we’re working on a tool to help facilitate that.”

And that, he adds, is the reason the research got its funding – the NIH wants this tool in its toolbox. The grant covers five years, but it’s been a seven-year journey to this point. It began with a discussion between Santangelo and Emory professor Eric Hunter, whose research is focused on the molecular biology of HIV and other retroviruses.

“We were sitting around a table and Eric basically said, ‘one thing we’d like to know is, where is the virus? Is there a way to image this?’ I said, ‘I have no idea, but let’s see if we can figure that out.’ So I went back to the drawing board and thought about ways to approach the problem,” Santangelo says. “But that’s how it started – a group of people sitting around the table, asking, ‘how do we address this?’ and me being crazy enough to say, ‘I’ll try this,’ because I don’t say no to anything.”

Hunter introduced Santangelo to researcher/pathologist Villinger. They went after and received a $30,000 boost from the Woodruff Foundation, then got $100,000 from the Georgia Research Alliance, “and these were so important in pushing the momentum forward,” Santangelo says.

Then they received $450,000 from the NIH in the form of an Exploratory/Developmental Research Grant Award (R21) and now, $5.5 million, to support the work of an all-star team of researchers, including (among others) principal investigators Santangelo and Villinger, as well as Ray Schinazi, who directs the Laboratory of Biochemical Pharmacology at Emory, who is a co-investigator.

The overall goal, according to Santangelo, is to create or improve an imaging tool that will determine how the virus is being affected by a new drug strategy, and also to help promote new drugs that Schinazi is working on – “to clear HIV, and also to make current drugs more effective,” says Santangelo, who believes that by enhancing current imaging technology, particularly CT (computed tomography, or CAT scanning) and PET (positron emission tomography), he can track the reservoirs, including active viral reservoirs.

“If you can figure out where the reservoirs are, if you can figure out how long they are being affected by the drugs, and how the drugs are actually changing the reservoirs, we might be able to clear them,” says Santangelo, who looks like a kid contemplating a super toy that hasn’t been invented yet. “And if you can clear these reservoirs, you could cure AIDS, and if you can cure AIDS, well, that would be pretty awesome.”

Seeds of Innovation

Three interdisciplinary teams with wide-ranging goals at the Parker H. Petit Institute for Bioengineering and Bioscience have gotten off to a fast start on pioneering explorations in biotechnology, thanks to a homegrown program that supports innovative early-stage research.

The winning teams of the 2014 Petit Bioengineering and Bioscience Collaborative Seed Grant are working to improve the prediction of disease (Hang Lu and Patrick McGrath), design better drug delivery strategies to fight cancer (M.G. Finn and Susan Thomas), and unveil (and better understand) the processes through which cell receptor signaling is initiated (Robert Dickson and Cheng Zhu).

Each of these fledgling collaborative teams was awarded $100,000 for two years to kick-start new research en route to long-range aspirations.

“The seed grant program is fantastic, because it supports bold ideas that don’t have preliminary data,” says Lu, a professor in the School of Chemical and Biomolecular Engineering. “Patrick and I have been wanting to work on this particular idea of evolving model systems to study multigenic diseases. We are extremely happy to have the support to pursue it now. We’re hoping to garner preliminary data to seek NIH funding in the long run.”

The program, now in its third year, gets to the heart of the Petit Institute mission, as it encourages a multidisciplinary approach to cutting-edge research, with each team bringing together an engineer and a scientist in a collaborative research endeavor, addressing complex biotech challenges by combining the distinct strengths of each lab. For example, as Lu and McGrath (assistant professor in the School of Biology) explain in their proposal, “Technologically and conceptually, what we propose here has never been done before. This pilot is truly enabled by the genomics know-how of the McGrath lab and the technological advancement of the Lu lab, which is a unique combination not found elsewhere.”

By applying a directed evolutionary approach, they expect to eventually be able to identify interacting genes that can be used as biomarkers for lifespan and age-related diseases, “and also as synergistic drug targets that can be used to ameliorate side-effects by lowering dose-levels of pharmaceuticals.”

Zhu, professor in the Wallace H. Coulter Department of Biomedical Engineering, he and Dickson, professor in the School of Chemistry and Biochemistry), are “trying to develop methods that allow in situ measurements of protein-protein interactions in live cells,” says Zhu. “The lacking of such methods hinders the development of a broad field in biology.” Currently, no method allows this kind of crucial measurement, Zhu and Dickson say in their proposal.

Meanwhile, Finn (professor and chair in the School of Chemistry and Biochemistry) and Thomas (assistant professor in the George W. Woodruff School of Mechanical Engineering) are working on a project with what they say will ultimately “impact the drug delivery field by introducing a new chemical means to temporally control drug release,” according to their proposal.

“In some ways, this approach runs counter to the prevailing drive in the field toward ever more sophisticated ways to respond to environmental cues,” the researchers say, adding, “While such technologies are undoubtedly valuable, there is also value in a cleavage mechanism that one can use like an alarm clock.” Stretching the analogy a bit further, they describe an alarm clock in which the start and end times, and intensity (and composition of the alarm) are all programmable.

“Results from this study,” Finn and Thomas say in their proposal, “will form the basis of numerous collaborative grant applications and a long-term collaboration between two labs with distinct but synergistic expertise aimed towards the design and effective drug delivery strategies for cancer therapy.”

Funding for the seed grants comes mainly from the Petit Institute’s endowment as well as contributions from the College of Sciences and the College of Engineering. Each research team receives $50,000 a year for two years, with the second year of funding contingent on submission of an external collaborative grant proposal.