Posted on Tuesday 24 December 2013

I’ve underlined everything new in this article as a reading aid:
New York Times
December 23, 2013

When will we ever get depression under control?

Of all the major illnesses, mental or physical, depression has been one of the toughest to subdue. Despite the ubiquity of antidepressant drugs — there are now 26 to choose from — only a third of patients with major depression will experience a full remission after the first round of treatment, and successive treatments with different drugs will give some relief to just 20 to 25 percent more. About 30 percent of people with depression have some degree of treatment resistance. And the greater the degree of resistance, the more likely a future relapse, even if the patient continues taking the drug.

Although we have learned much about depression — for example, the recent research showing that the successful treatment of insomnia in depressed patients essentially doubles their response to a drug like Prozac — we still don’t understand its fundamental cause. The old idea that the disease results from a deficiency of a single neurotransmitter like serotonin or dopamine is clearly simplistic and wrong… Not long ago, I sat in at a meeting of the Hope for Depression Research Foundation. Audrey Gruss, the knowledgeable and energetic philanthropist who started the foundation, has corralled a group of senior basic and clinical neuroscientists to look for solutions. [It is not the first to try a collaborative approach; others are being sponsored by the MacArthur Foundation and the Pritzker Consortium.]

“A complex problem like depression is much larger than one scientist or lab can handle,” said the leader of the group at the Hope foundation, Huda Akil, a professor of neurosciences and psychiatry at the University of Michigan. “What is great about our collaboration is that we can think about big ideas and take risks without worrying about what grant reviewers” — like the National Institute of Mental Health, the major source of federal funding for psychiatric research — “might think.” A major goal is to understand which brain circuits and genes are altered by depression, how the environment interacts with these genes, and how to reverse the accumulated biological assaults of this disease. That will require the integration of a wide range of tools, she said: genomics, epigenetics, electrophysiology, animal models, clinical psychiatry.

A major drawback of our current antidepressants is that they rely on animal models that have been used for decades, yielding drugs that all work the same way. Novel drugs require identification of new targets in the brain and better animal models in which to screen them. So one member of the group, Dr. Joshua Gordon, an associate professor of psychiatry at Columbia, studies new animal models of depression by recording activity in select brain regions in mice that are engaged in depressionlike behavior.

After talking with another group member, Dr. Helen S. Mayberg, a neuroscientist at Emory University, Dr. Gordon modified his approach. Dr. Mayberg has identified a target for deep brain stimulation in patients with treatment-resistant depression: a region called the subgenual cingulate cortex. When it is directly stimulated with electrodes in depressed patients who have failed to respond to nearly all other treatments, many show a brisk positive response. Dr. Mayberg urged Dr. Gordon to extend the region of his recording to include the mouse analog of this human brain region, so he could more fully capture activity in these different areas of the cortex and understand how they individually contribute to depressionlike behavior in mice. Another group member, Bruce McEwen, a neuroscientist at Rockefeller University who has done pioneering work on the effects of stress on the brain, is studying rats from Dr. Akil’s lab that have been genetically selected for their propensity to show anxiety and depressionlike behavior.

Among other things, Dr. McEwen is using these rats to study the efficacy of drugs with the potential to act rapidly against depression. Such a drug would be a major boon to psychiatry: We need treatments that can ease the symptoms of depression, and its attendant risk of suicide, in far less time than the two to six weeks that all current antidepressants require to do their work.

Even a high-powered collaboration like this one offers no guarantee of finding effective weapons against intractable depression. After all, it took 50 years to smoke out the Higgs boson, and even at that, there are huge unanswered questions. But at a time when federal research funds are shrinking and major drug companies have all but shuttered their brain research programs, enlightened philanthropists and entrepreneurs are helping to open a promising new pathway for neuroscience research: collaboration among researchers willing and able to take thoughtful risks and solve big problems.

The point of any taxonomy is to iterate large categories towards increasingly homogeneous  subgroupings that can be researched in pure culture. The creation of Major Depressive Disorder with the DSM-III thirty-three years ago did the opposite, destroying that process and setting the stage for one of medicine’s all time misadventures with its monotonous waves of new foci. But that’s old news [as is this article about a new focus on depression]. Nothing new up there we haven’t heard for years. Just the inertia of a generation of academic psychiatrists who have known nothing else. But they unfortunately threw out many of the clinicians who form the backbone of any medical specialty, and psychiatry became increasingly experience distant from patients [often treated more like subjects in an endless clinical trial]. But that’s old news too.

Perhaps a more interesting question is, why is this article even in the New York Times? It can hardly be considered News. No articles about the dilemmas of any other medical specialties – just this one from psychiatry about drug research. I guess it’s another commercial – designed to attract other enlightened philanthropists and entrepreneurs into investing in neuroscience research. There’s nothing wrong with trying to raise independent money in lieu of the drying up NIMH and pharmaceutical funding. But once again, it’s a disguised sales pitch from an academic psychiatry professor selling futures. It would seem wiser to step back and re-evaluate the whole enterprise and why so much has been spent with so little to show for it rather than press ahead with what we’ve been doing for years. The interest and the money has dried up for a reason…
    Bernard Carroll
    December 25, 2013 | 12:44 AM

    Wise man say: the name of the game is to keep the game going.

    December 25, 2013 | 4:46 AM

    “”Although we have learned much about depression — for example, the recent research showing that the successful treatment of insomnia in depressed patients essentially doubles their response to a drug like Prozac — we still don’t understand its fundamental cause””

    Maybe if Dr. Friedman did more research of sleep medicine in general instead of thinking that a drug is the answer to everything, he would realize that many people are cured of their depression and no longer need meds once their insomnia is correctly diagnosed. And many people turn out to have sleep breathing disorders.

    No offense Dr. Nardo but asking psychiatrists to stop thinking that meds are the answer to everything and to actually believe that many psych conditions have physical causes is like asking kids to stop believing in Santa Claus/

    December 25, 2013 | 4:56 AM

    Forgot to wish you a happy holiday season, Dr. Nardo and thank you so much for this wonderful site.

    Berit Bryn-Jensen
    December 25, 2013 | 6:44 AM

    Happy Christmas, dr Nardo, and I second AA: “Thank you so much for this wonderful site”.
    Best wishes from this stormy, record wet season in Norway. Huge changes are afoot, though big, deluded trolls are always the last to see what waves are lapping at the shores.

    December 25, 2013 | 9:52 AM

    i suspect the article is a accolade for:

    “Hope for Depression Research Foundation. Audrey Gruss, the knowledgeable and energetic philanthropist who started the foundation”

    “enlightened philanthropists and entrepreneurs are helping to open a promising new pathway for neuroscience research:”

    December 26, 2013 | 5:42 PM

    Working three minimum wage jobs to barely scrape by is depressing. Being bullied is depressing. Being a victim of domestic violence is depressing. Being a victim of rape is depressing. Not having the money it takes to hire a good lawyer so you could afford justice is depressing. Not having any savings is depressing. Having your savings wiped out by a loved one’s funeral is depressing. Being an alcoholic is depressing. Untreated or poorly treated chronic pain is depressing. Being addicted to drugs is depressing. Not being able to take time off of work and take care of yourself when you’re sick and/or overwhelmed is depressing. Losing your home to a financial collapse, hurricane, or tornado and not having the means to recover is depressing. Losing everything you’ve worked for all your life is depressing. Being treated like crap by your boss and customers all day, every workday, is depressing. Knowing that you’re one paycheck away from the skids is depressing. Knowing that the chances that you’ll move up to the middle class aren’t much more likely than your chances of winning the lottery is depressing. Working harder and longer every year for less and less for decades is depressing. Fighting with your spouse regularly over what to do with what little disposable the two of you have is depressing. Getting divorced is depressing. Not having money to provide well for your children is depressing. Tens to hundreds of thousands of dollars worth of debt for a college degree and no jobs is depressing. Being illiterate and not having a high school diploma is depressing. Having chronic dental problems and not being able to afford a dentist is depression. Being in a serious car accident is depressing. Having an unidentified medical illness being treated as depression while suffering the effects of useless drug cocktails that interfere with cognition and emotional regulation while making you obese and diabetic as your untreated medical condition rages on untreated is depressing. Having not one real and reliable friend is depressing and is a health hazard. Living in a polarized, paranoid, wealth worshiping society that hates minorities and the poor is depressing.

    Wealth disparity at record highs and KOLs getting rich from labeling misery as depression and offering it nothing more than lousy drugs and blame for the sufferer is infuriating.

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