Reflection on Depression

A Must Read: Genetic Breakthough in Depression Research

Scientists at two universities, working independently, studied families with a history of severe recurrent depression and found that variations on a region of chromosome three are linked to the disorder. The discovery is hard evidence that depression (at least this type of depression) is partly a genetic disorder. The researchers are now looking at this region of DNA to identify the specific genes involved. Although treatments based on this research are probably more than decade off, it's exciting to find such a specific causal factor.

Major breakthrough in genetic research into depression

Dr. Owen Wolkowitz on depression

This talk by Dr. Owen Wolkowitz at UCSF is one of the best talks on the science of depression that I've ever seen.  Even though it is targeted to a general audience it gets across a lot hard science, including some of the newest research on epigenetics. Very interesting and worth a watch!

Dr. Wolkowitz on the biology of depression

 

FDA advisory panel requires new testing of ECT machines

I finally had a chance to catch my breath at work and can get back to blogging! There's a lot to catch up on because a number of interesting mental health issues have been in the news. In particular, this article describes last week's meetings of an FDA advisory panel to review the classification of ECT (electroschock therapy) machines.  

When the FDA put the current medical device rating system into effect in the 1970s it rated ECT machines as Class III devices, meaning rigorous safety testing should have been required for market approval. However, ECT had been around for decades and so the FDA grandfathered in the machines to exempt them from costly new trials. Recently, the Government Accountability Office eliminated this grandfathering, forcing the FDA to either reclassify the devices--in effect lowering restrictions--or require new (and costly) safety tests.  After two days of meetings the advisory panel decided to maintain the Class III rating.  As a result, new safety trials are necessary to keep the machines on the market. 

Psychiatrists worry that there could be an incipient ECT "shortage" because the two companies that make the devices may be not be able to afford the necessary clinical trials. Most patients' rights groups, however, are pleased with the FDA's decision to require new testing.  These ECT "survivors" are concerned about memory loss, ECT's most severe side effect, and would like to see more data on the efficacy/safety profile of the treatment. 

This tension between short term need and long term understanding is difficult to resolve. My first thought was that the FDA should have reclassified the devices in order to keep ECT widely available because ECT is thought to be the most effective and fastest acting treatment for severe depression. Eliminating it as an option is like taking morphine and other powerful painkillers away from doctors, asking them to rely on over-the-counter painkillers instead. The FDA, however, is taking the long-term view that new testing will ultimately clarify the risk/benefit profile of the devices, allowing doctors to make more informed decisions in prescribing the treatment. 

The new trials will have to be financed by a deep pocket--probably the government since ECT machine manufactures may not be able afford the clinical trials themselves. Let's hope the trials happen and, in the long run, we have more information about a treatment that (historically at least) has been a critical item in psychiatrists' tool kits. 

Outstanding Charlie Rose episode on mental illness

Here's a link to an excellent episode of Charlie Rose that features nobel laureate Eric Kandel, Helen Mayberg (an expert on deep brain stimulation for depression), Elyn Saks (a law professor and McArthur Genius Grant award winner who has schizophrenia), and Kay Redfield Jamison (bipolar patient, bestselling author, and a professor at Johns Hopkins Medical School).

These are four of the most outstanding mental health advocates and researchers in the world, all of whom are very articulate authorities on mental illness. Kay Jamison makes some especially insighful comments on the difference between depression and grief in this episode.

Research reveals genetic similarities common to schizophrenia, anxiety disorders, and depression

An interesting study funded by NARSAD found that a genetic mutation in male mice predisposing them to schizophrenia also makes them more susciptible to depression and anxiety. 

Based on my own experience I think these disorders are related. Not only do the same symptoms seem to show up to different degrees in each disorder, but many of the same medications are used to treat the various conditions. I would be surprised if there were not some common underlying etiology. It's bound to be complex and difficult to untangle, though.

Dwight Schrute's depression cure

Maybe Dwight was on to something when he suggested hand de-sanitizing stations in an episode of The Office a few weeks ago. Modern coddled immune systems may explain why depression is more common in younger cohorts than in older folks who grew up exposed to more bacteria.

Is depression increasing because we are no longer exposed to the right bacteria?

On a more serious note, research examining the relationship between inflammation and depression has gotten a lot of publicity recently. One line of research is looking at the role of cytokines (molecules produced during an inflammatory response which act on the brain) in causing depression in patients who suffer from chronic inflammatory diseases.

Another line of investigation posits that depression may result from brain inflammation caused by a normal neural remodeling process gone awry. 

My first episode of depression was preceded by mono--something my parents and some doctors remained convinced triggered its onset. I don't think that's the whole story (I suspect I also had some underlying vulnerability), but it's an intriguing possibility.

DSM V - FAIL

I have issues with the DSM-IV, and it looks like they aren't going away when the new DSM-V is published in 2013.  The DSM (Diagnostic and Statistical Manual of Mental Disorders) is a sort of pseudo-scientific classification of behavioral and mental disorders based on clinical presentation (not based on well-understood underlying etiology).  Obviously, coming to some kind of agreement on what constitutes a particular disorder like depression is a challenge when we don't really know what depression actually is.  It's probably a heterogeneous set of disorders, and not a single disorder on a continuum from mild to severe as the DSM posits.

I appreciate the work of the clinicians and academics who are trying to formulate a workable and accurate classification system based on poorly understood phenomena.  It has to be a thankless task.  At best, the results will be mediocre (since the results can hardly exceed our limited understanding of mental disorders) but the work is still necessary--it's presumably better than nothing.  After all, how would we carry out research that can be disseminated and compared without any standard classification system?

That said, the current revisions that will lead to the DMS - V are proceeding in a particularly contentious manner. Cloaked in secrecy, criticized openly by some participants, and behind schedule, the validity of the new DSM is already an open question.

See this article about missed deadlines and shoddy work product for a quick rundown of some of the problems the DSM-V writers face.

 

New genetic link to depression discovered

New genetic link to depression discovered

Good news:  A post-mortem analysis of the brain tissue of both depressed and nondepressed subjects found that the level of a gene that inactivates a process crucial for neuronal survival is twice as high in brains of the depressed subjects.  The gene is also implicated in other brain disorders.  

Bad news:  I could have too much a gene that makes it harder for my neurons to survive!?! Not good. I need my neurons, I'm a lawyer. Let's hope SSRIs really do stimulate neurogenesis.

Overall, I'm really excited to see so much basic research being done on new mechanisms of depression and depression treatment, and on newly identified genetic risk factors.  It's about time we move beyond the "chemical imbalance" paradigm.

 

Depression in Preschoolers

An article in Sunday's New York Times asks if prechoolers can suffer from depression. The answer, I think, is obvious to anyone who concedes that depression is a physiological disorder. If biological mechanisms really mediate depression--or at least some types of depression--then children almost certainly get depressed. In fact, how could depression not show up in at least a small percentage of young children?

Sure, stress is the major trigger for depression and young children usually haven't accumulated enough to trip the genetic wire that turns on the illness. However, it's likely that some children have experienced enormous stress at a very young age through neglect, physical illness, or trauma. Others may be genetically predisposed to develop depression in response to even normal stresses.

Take also the small percentage of depressions caused by gross morphological disturbances--head injuries, brain tumors, shaken baby syndrome, etc., and a number of young children must be suffering. Thus, a biological model of depression, while it predicts that depression is rare among young children, nevertheless acknowledges that it almost certainly exists. Like early childhood cancer, depression is rare but possible.

Those who disagree point out that children lack the self-awareness required to experience depression. After all, children so young are just learning to recognize themselves in a mirror. How then, could they possibly experience a fundamental collapse of self-esteem like in depression?

The answer is two-fold. On the one hand, depression (at least the severe biological depressions) are largely physical. As anyone who has experienced one can tell you, a general body ache--a malaise--accompanied by an extreme loss of appetite and brutal insomnia come with depression. Depression also slows down movement dramatically, and it dampens the voice to a raspy whisper. Given that the gut contains more neurotransmitters than the brain, it's not unusual for the depressed to develop constipation (this symptom is especially common in psychotic depression). In short, the constellation of physical ailments comprising depression is one that children, no matter how young, can experience.

Second, the mental symptoms of depression are primarily emotional, not cognitive. Neuropsychologically, depression arises from the reptilian limbic system with which children are born. While they may not experience symptoms like loss of self-esteem and loss of concentration that stem from higher-order cognitive faculties tied to the late-developing pre-frontal cortex, it is entirely plausible that children suffer from dysregulation of the limbic system. And given that they cannot moderate these emotions as well as adults, depression may be very pronounced in small children. 

Diagnosing depression in children, however, is a tricky issue. They do not verbally express their symptoms in the same way as adults (if at all).  Likewise, more than expressions of sadness, common symptoms among children are heightened irritability and complaints of boredom. Of course, irritability, temper tantrums, emotional dysregulation, and a short attention span are characteristic of all young children. When should parents, teachers, and doctors start to worry? There's not an easy answer--for first-time parents the issue is doubly hard because they have no basis of comparison. So, while depression in children exists as certainly as childhood cancer, diagnosis is tricky.  As for treatment???  That's a whole other post--nothing incites debate like giving antidepressants to children.

Vagus Nerve Stimulation for Depression

Vagus nerve stimulation is a fairly new treatment for depression that involves stimulating the vagus nerve in the neck with an implanted electrical device. It's not known exactly how this affects the brain, but the treatment has proven effective for both depression and certain types of epilepsy, and is FDA approved for both indications.

I hear less about VNS than other new treatments like TMS (transcranial magnetic imaging) or DBS (deep brain stimulation). For some reason it doesn't seem to get as much attention--perhaps because VNS produces undesirable side effects in some people--apparently it can affect the voice box, making it difficult for patients to speak clearly. However, the procedure has cured some sufferers. When I looked for an explanation of VNS on youtube I found this clip accompanied by comments from people who have had good experiences with it.

Unfortunately, it costs tens of thousands of dollars, but one commentator was able to get the procedure in India for a fraction of the price in the U.S.  That's risky, but he had a family member who was a doctor India, and so was able to navigate that county's healthcare system safely.

One thing I like about this video is that the doctor readily admits that we don't know what depression is.  That's so true!  It's likely a number of different disorders, which is why different people respond to different treatments. Right now, he also admits, we don't know how exactly VNS works, but it has proven effective and relatively safe so it's worth a shot for many people.