The New York Times science section today features an essay on the long-term use of antidepressants. The lead refers to the sort of question I introduced in Listening to Prozac: how do these medications shape identity? But most of the piece concerns the biological effects of taking the drugs for years.

The author, Richard A. Friedman, quite properly says that we do not know about the effects of extended use and calls for better post-marketing studies. This point cannot be emphasized enough. Since we have vast numbers of people on antidepressants chronically, it is irresponsible for us as a society not to examine the medications through multi-year studies. This kind of research is hard to motivate; few young scientists in need of publications choose to undertake work whose results will emerge far down the road. The Food and Drug Administration, which has taken baby steps in this direction, should be mandating the relevant investigations; the National Institute of Mental Health should be supervising them.

Because his patient, now 31, was an adolescent when she first took Prozac, Friedman mentions research about suicidality, pro and con ? but presumably he knows whether his patient is at risk. She was suicidal before taking medication but not since. Likewise, he refers to the studies I have discussed here and elsewhere repeatedly that show a bias in the publication of short-term drug trials; positive, but not negative or equivocal, outcomes tend to find their way into print. Again, this concern has little to do with Friedman?s patient. Whatever the odds for the average person, Friedman?s actual patient responded to medication. For her, the widely publicized concerns about new-onset suicidality and overall efficacy are red herrings.

Friedman?s case presents the most usual scenario. On medication, a patient gets better. She experiences few side effects, or only ones that are tolerable in the short run. Then, the disease recurs, and the patient requires longer intervals of treatment. Side effects like loss of sex drive become troublesome. Now, issues of the unknown enter in: What does it mean, psychologically and physiologically, to be on a medication for years?

If I were allocating resources for research on the medications we have to hand, I would put a fair proportion here, into investigating what it means for any patient, adolescent or adult, to take antidepressants for much of a lifetime.

Note added 4/22: For thoughts concerning possible beneficial effects of long-term antidepressant use, see my more recent posting on medication and resilience in the brain.

A number of small studies claim that art therapy reduces depression through helping people with mood disorders resolve emotional problems and release repressed feelings. But maybe that is not really why art making helps to alter mood. The answer may literally be in your hands.

In a recent post, ?Where Depression Might Reside,? Peter Kramer notes that both researchers and clinicians are increasingly pointing to an area of the brain known as the frontal cortex. In a similar vein, psychologist and neuroscientist Kelly Lambert proposes that the accumbens-striatal-cortical network?a system in the brain that connects movement, emotion, and thinking?is the underlying source of symptoms associated with depression. While the pre-frontal cortex in linked to the inability to concentrate (a symptom associated with depression), there are other parts of the brain that are involved, too, according to Lambert?s research. Those areas account for slow responses (accumbens), perceived loss of pleasure (striatum), and negative feelings (limbic system). These areas form what Lambert defines as the effort-driven rewards circuit.

What interests me as an art therapist and expressive therapist is Lambert?s finding that a well-engaged ?effort-driven rewards circuit? helps us effectively meet emotional challenges, thus ameliorating depressive symptoms to some extent. Brain-wise, moving our hands activates larger areas of the cortex than movement of other parts of the body such as our legs or back muscles. And more importantly, what drives that effort-driven rewards circuit are physical activities that involve our hands, particularly activities that produce tangible products that we can see, touch, and enjoy. While Lambert mentions knitting or tending a garden as effort-driven reward-giving activities, I can?t help but think that this brain-hand connection applies to art making as well. ?Making things? such as a drawing, painting, collage, weaving, or sculpture involve hands-on investment in an object with tangible results that give pleasure to or have meaning for their creators.

My arts in healthcare colleague Ellen Dissanayake says that art making evolved not only out of psychological need, but also as a ?proto-aesthetic operation? involving using one's hands for elaboration, repetition, and manipulation, starting in early childhood. Ellen?s theory is based on how cultures throughout history have used the arts for connection, communication, and curative powers. In contrast, the 21st century seems to be a time that Blackberries and cell phone, computer, and plasma screens increasingly take humans away from those physical, effort-driven, proto-aesthetic operations ? in short, away from making things for pleasure, reward, and meaning. Lambert claims, and perhaps rightly so, that this contemporary trend is sapping our mental well being and reducing an innate resistance to depression.

So does ?making things? offer a possible intervention for depression? It seems it might, at least as part of a program to treat what is not always alleviated by pharmacology plus talk therapy. While the arts serve as a means of self-expression and perhaps emotional reparation, we humans have consistently returned to the pleasure of crafting things with our hands for some more fundamental reason. Lambert?s research also brings new questions to the perennial debate about connections between depression and artists (more about that in a future post). But for now, it is exciting to know that we all may have access to an internal effort-driven rewards circuit to simply chase our blues away.

© 2008 Cathy Malchiodi

www.cathymalchiodi.com

Say that in the current financial turmoil you lose your job or your nest egg and respond by manifesting the signs and experiencing the symptoms of a depressive disorder: are you depressed? Yes, very likely you are, according to the way doctors currently diagnose mood disorder. No, say certain critics who believe that most ?caused depressions? are better understood as mere sadness. But the naysayers? case took a terrible blow this past month, in the form of a study that examines the varieties of grief.<!--break-->

For the research, Kenneth Kendler, a psychiatrist and perhaps our leading behavioral geneticist, joined Sidney Zisook, author of an important paper on the use of antidepressants to treat grief-related depressive symptoms. The team looked at the relationship among normal grief, apparent depression arising from bereavement, and diagnosable depression arising from other stressors.

The findings are finally too detailed to be conveyed in a brief summary, but the researchers arrive at what in the scientific literature counts as a forceful conclusion: ?[B]oth this study and our recent literature reviews suggest that bereavement-related depression is probably similar to other forms of major depression. Bereavement-related depression is recurrent, genetically influenced, impairing, and treatment-responsive. These are all characteristics that are more likely to be associated with major depression than ?normal sadness.??

Looking at members of twin pairs, the researchers examined 82 subjects whose depressive symptoms arose in response to loss of a loved one and 224 subjects whose depression related to other stressors. There were some differences, but the between-group similarities were much more striking.

In particular, when compared to subjects with stress-associated depression, people with grief-driven depression had the same age of onset, the same number of prior episodes, the same indicators of risk for future episodes, and ? get this! ? the same risk of depression in a co-twin. Even those depressed-and-bereaved subjects who met criteria for ?normal grief? had the same heightened level of depression in co-twins. That is to say, people who respond to bereavement with depression are subject to the same genetic risk that drives depression altogether. Those subjects whose episodes looked like ?normal grief? (with a short duration and lack of suicidality), also looked ? simply depressed.

This study is not utterly conclusive, but a fair reading says that it casts a deep shadow on an argument that?s gotten altogether too much press. Readers of this blog will recall that the theorists Allan Horwitz and Jerome Wakefield champion a line of reasoning that runs like this: In defining depression, psychiatry makes an exception for normal bereavement. If you?re in grief, even if your grief has all the symptoms of depression, you?re not depressed. Why not make a similar exception for any stressor, so that if your grief arises from divorce, you?re considered merely sad?

Those interested in a thoroughgoing answer to this challenge, should look at an address on the subject that I gave at Rutgers University. In part, I said, ?In behavioral genetics, where it is critical to distinguish subtle signals from loud noise, researchers tend not to exclude bereavement. If stress triggers depression, the result is counted as depression. The character of the stress is irrelevant.? The data is simply more consistent ? you stand more of a chance of finding relevant genes ? if you count grief-related depression as depression.

The current Kendler-Zisook study justifies this practice. The authors conclude: ?These results question the validity of the bereavement exclusion for the diagnosis of major depression.? That was the result I (and many others) had predicted. In part because there are a few distinctive features of bereavement, but mostly for political reasons ? expanding depression to include depressive forms of bereavement simply makes people uncomfortable ? the bereavement exclusion will likely linger on in the diagnostic manuals. But when scientists are being frank, they say that there is no paradox: stress-triggered depression is depression, conveying all the risk of depression, from suicide to heart disease to recurrent episodes. Bereavement acts like other stressors, bringing forth a dangerous syndrome in those who are vulnerable on the basis of genetics or prior experience.

Ronald Pies, my former colleague on the Psychiatric Times and now its editor (congratulations, Ron!), gives a mild rejoinder to Wakefield and Horwitz in today?s Science Times. I wish that Pies had included this new finding from behavioral genetics. The ?mere sadness? hypothesis was already shaky on any number of grounds. This new research knocks the legs out from under the one argument that was distinctive. Yes, the Kendler-Zisook study says, the response to bereavement does often look like depression ? because bereavement often results in depression.

Note: As a reader (below) correctly points out, when I first posted this comment, I misidentified the professional training of the behavioral scientists Horwitz and Wakefield; Horwitz is a sociologist and Wakefield, a social worker. My apologies.

The prevailing contemporary model for depression suggests that in vulnerable people, repeated stress gives rise to adverse changes in the brain; depression is itself a stressor. The primary evidence for this hypothesis comes from rodent studies, where early deprivation and later mild stress cause what look like mood changes - and shrinkage in areas of the brain that correspond to our hippocampus and prefrontal cortex. Human studies have tended to be correlational: patients who have suffered more days of mood disorder have more differences in brain volume. These findings are ambiguous. Perhaps a person with a small hippocampus is more prone to depression.

Evidence for the second theory, in which small hippocampal size creates vulnerability, came from the laboratory of the German psychiatrist , Thomas Frodl. He found that over the course of a year, chronic depression did not predict hippocampal change, but small hippocampal size predicted chronicity of depression. That's what makes a new study particularly intriguing. Looking now at a three-year interval, Frodl has found that depression does lead to loss of volume in critical regions of the brain.

The study contrasted 38 patients hospitalized for depression with 30 matched controls and used MRI scans coded by new software technology that distinguishes changes throughout the brain, not just in areas pre-selected by researchers. Over the next three years, the patients, and not the controls, showed a "decline in gray matter density" in the hippocampus, prefrontal cortex, and elsewhere. There was no part of the brain where the depressed patients showed increased volume or density. Patients whose mood disorder had remitted showed less volume decline. Overall, Frodl concluded, this prospective study in humans supports the findings from animal models in which stress and depression-like disorders cause brain change.

In the just-published study, antidepressants did not have a separate effect - it was getting better that conferred some protection. But the month before, in September, Frodl contributed an analysis showing that in some patients who took antidepressants for the whole of three years "hippocampal volumes increased significantly." A critical interactive factor may have been hippocampal size at the start of treatment. (It should be said that this study had a high attrition rate; its conclusions are necessarily speculative.) In the September paper, Frodl concluded that "a relatively small hippocampal volume may be a vulnerability factor for a bad treatment response in major depression."

Both may be true: depression attacks the hippocampus, and a small hippocampus impairs resilience. In Against Depression, I wrote that the evidence favored this combined hypothesis - so the theory is not new. But Frodl's current research does point to movement in the field toward the conclusion that depression or stress in the presence of depression injures the brain. That model suggests a need for vigorous early intervention and extended treatment. Recovery seems to offer some protection. Although the evidence is hardly clear-cut, long-term antidepressant use may as well.

Those long days just feel good. I had new energy, fresh ideas - well, perhaps one does on vacation anyway. But surely sunshine helps.

That's what I tell patients when I recommend bright lights here at 41 degrees 49 minutes north, where (today) the sun sets at 4:29 PM and civil twilight ends at 5:01. Run 10,000 lux for half an hour in the morning, let your brain imagine you're a bit further south, and you'll perk up.

I know, I know. The evidence is weak that bright lights help straightforward major depression, the type that's not clear-cut seasonal affective disorder. (See here and here and here; for a more upbeat reading of the data, see here.)

But light therapy has become less expensive. The sorts of devices that once cost $300 and up are now available through Amazon and big-box discounters for under $160. The lights are less clunky and more portable than they once were - sort of cool-looking, actually, so your dormitory roommate might be jealous rather than scornful.

If I sound like a salesman - that's because I am repeatedly amazed at how resistant depressed patients can be to trying a low-tech approach to mood disorder. After all, some people do simply live further south. But then, in depression, it's hard to make any effort, and hard to hope.

Anyway, that was one of my thoughts as the sun rose over Lago Nahuel Huapi - long days are easy to live with. As for the artificial version: often, the lights help. Even when they don't, people like the feeling they give; and in the midst of depression, a little pleasure can be a great boon.