Wednesday, March 10, 2010

Man's Search for Meaning

Man's Search for Meaning, by Victor Frankl, is one the great books of the past century. 

Frankl (1905-1997) was an Austrian psychiatrist who developed a style of therapy which he called "logotherapy," a style which focuses upon the identification and nurturance of meaning as a primary therapeutic goal.  While this style affirms the importance of symptom relief, it focuses on the idea that meaning is available even in the context of extreme unremitting symptoms or suffering.

The gravity of his ideas must be taken very seriously, because of Frankl's own personal experience between 1942-1945:  he survived almost three horrific years in Nazi concentration camps including Auschwitz and Dachau.  His parents and wife were killed in the concentration camps, and his only surviving immediate relative was one sister.  So Frankl approaches these questions with the perspective of one who understands the extremity of suffering, profound loss, and domination by oppressive forces outside of one's control.   In this way, Frankl has a deep empathic understanding of what it can be like to experience severe, torturously unremitting psychological illness. 

The first half of Man's Search for Meaning is a description of life in the concentration camps.  The second half is a brief description of the author's meaning-based psychotherapy style.

As a style issue, I do wish there was more attention to gender-inclusive language, as humans are always referred to as "man," and the pronoun "his" is always used instead of "her."    But this is a very small complaint, given the profoundly moving, inclusive, and life-affirming nature of this writing. 

This is another of the books I've read recently, which I really ought to have read 20 years ago...

Monday, March 8, 2010

Losing at the Olympics

This subject has come up many times in conversation, over the past month.

The comments go something like this:

(referring to someone who has lost at the Olympics, and therefore did not get a gold medal, or any medal at all, etc.):

"What an incredible waste -- a waste of time, a waste of effort, to train all those years, to get all the way to the Olympics, to base your whole life on excelling in your sport, only to lose at the end!"

It seems to me that children or adults who have grown up being involved with athletics, and who have had good coaching over the years, have gained a good understanding of this issue (at best, I think athletic involvement can help considerably with personal growth).  Their response might be something like this:

"It is a joy and an honour to participate in the sport.  To play at all is meaningful.  To train for something is an intrinsic joy.  To be part of a community event, whether at a local community arena, or at the Olympics, is exciting, fun, and meaningful.  The meaning of all those years of training does not depend on winning a medal (although a medal would be nice!) -- all that training was an act of love, my life has been better because of it, regardless of any medals."
Most of the Olympic competitors were very gracious and honorable in their wins or losses.  The occasional individuals who were not gracious were really the only ones who "lost."  

Of course, there are issues about financial compensation, future career opportunities, etc. which may depend on winning, in one form or another.  And it could be deeply disappointing if a particular goal is not reached, and may not ever be reachable again (e.g. to make the Olympic team, to win a medal, etc.).


But psychological health cannot depend on such things.  I don't believe that Olympic athletes experience significant depressions due to losing...because the joy & meaning do not depend on winning or losing, they depend on the process.

Few of us are Olympic athletes, but we all have analogous life pathways...many of us view life success as dependent on some external "win" such as getting high grades, getting into the right school or program, getting the best job, having money, car, house, relationship, being a certain body type or weight,  etc.

Provided that an individual is not in an impoverished state (financially,  nutritionally, neurophysiologically, psychosocially, etc.), I claim that success in life is dependent on process, not on winning anything.  While the pursuit of excellence is itself a healthy and enjoyable process, it ironically cannot proceed if the pursuit of excellence becomes frozen into a pursuit of "winning."  Winning will happen, on multiple levels, if a joy of process is nurtured.

Wednesday, March 3, 2010

Book Review: Mad, Bad and Sad

Mad, Bad, and Sad: A History of Women and the Mind Doctors from 1800 to the Present, by Lisa Appignanesi (2007) is quite a good history of psychiatry, particularly regarding the period between 1800 and about 1950.

It was interesting and valuable to look at some of the life histories of individual women from previous eras, and to speculate about what helped them and what did not. Some of the biographical sketches are about famous women such as Sylvia Plath, Virginia Woolf, and Marilyn Monroe.

The author approaches the subject matter with a broad vision to include social and cultural context, and particularly feminist issues such as the role constraints and expectations imposed upon women by the prevailing culture, in communities, in families, and also in the therapeutic relationships (which often had a paternalistic quality, or one which reinforced restrictive cultural stereotypes about women).

Many of the stories are strong critiques against various elements of therapeutic philosophy and practice, especially biological psychiatry.

An important thesis is of the limitations of "therapy": her closing statement is
...the mind doctors--whether they're GPs on the front line, therapists of an increasing number of varieties, psychoanalysts, psychiatrists or psychopharmacologists -- trudge along, doing what they can, which is sometimes all that can be done. The danger, perhaps, comes when we ask them to do too much. (p. 484)
Certainly, through all the stories mentioned, the benefits of therapy were often tangible but limited--some compelling "success stories," others particularly tragic in their ending (e.g. Plath, Woolf, or Monroe).

An underlying thesis seems to be very supportive of psychoanalysis as an important form of therapy, which may nurture a sort of freedom in self-development and personal growth.

I find that she is excessively dismissive of cognitive-behavioural therapy. While I agree that such "shorter term" therapy styles may well be designed to improve symptom scores, such that an insurance company would be more willing to fund this therapy for a short time, then cut people off--I also think that many psychological ailments can be products of simple symptoms which can be treated in a very direct, matter-of-fact way, rather than through years of philosophical rumination on a psychoanalyst's couch. Panic attacks, OCD, social anxiety, etc. can be approached as symptoms which can be mastered through behavioural practice. It could be a tremendous disservice to individuals seeking "freedom" or "liberation" to neglect these practical and philosophically simple techniques.

I do agree that complex existential and relational issues can usually not be addressed in a shorter course of therapy, especially if the therapist is dogmatically attached to a particular style (e.g. in formal CBT, there may be no time to talk about any transferential issue or existential problem). Yet, many people may feel empowered to develop their existential and relational life on their own, provided that symptoms are not obstructing their efforts.

Some of her comments can be quite dismissive, for example:
But what young person doesn't feel depressed?--particularly perhaps after a week of student exams, or a split with a boyfriend, even after a little use of recreational drugs and forgetting to eat...A sense of hopelessness, a teenage irritability, may be a phase, even if one that lasts several years...One of the effects of such tools as the Beck's [sic] Depression Inventory and the DSM's chartable diagnoses is that they can produce the very results they are looking for. (pp. 468-9)
In response to this quote, I would say that we are dealing with semantics to some degree. Actually, most young people do not feel depressed after their exams. They do not have a sustained change in behaviour after relationship disappointments, do not have a prolonged sense of hopelessness, irritability, insomnia, weight loss, suicidality, etc. These feelings may well be "phases," but the question is, should we simply treat these as "normal," (which is a semantic construct itself), and therefore not "do" anything (i.e. not offer companionship, support, advice, mentorship, etc.)? I agree that labeling and medicalization may unreasonably guide people into reflexive and sometimes unhelpful or inappropriate treatments (e.g. if a certain Beck score or life disappointment would automatically necessitate antidepressant drug therapy without any opportunity for dialog).

The author appears to have a particularly narrow view of some psychiatric treatments, such as ECT, which she describes as "barbarism." (p. 480) Perhaps thoracic surgery could be judged barbaric as well--most types of medical treatment were truly barbaric in many previous points of history, and only became less so through understanding and careful research as to how to perform the treatments more safely. Undoubtedly, even today, many people have negative experiences with thoracic surgery--or ECT--but in order to evaluate the humane usefulness of such invasive procedures, we need to do careful research trials. In order to assess whether something is "barbaric" or not, perhaps it is important to examine the stories of those who have had a profound, life-saving experience of something, alongside the stories of those who have had ambivalent or negative experiences.

She attempts to be fair in her analysis of medication treatments, but I think most readers unfamiliar with the issue would read her analysis, and conclude that medications to treat depression are a dangerous sham perpetrated by drug companies, with the collusion of paternalistic and impatient physicians.

There is little discussion of vast areas of research about the human mind: the entire field of academic & research psychology is barely mentioned. This research is so very important in challenging the dogmas associated with various therapeutic theories. Psychoanalytic theorists may have been, and still are, very wise and very talented listeners or shamanic figures, but the theories themselves were, and are, often very weak if taken too literally, and sometimes cultishly dogmatic, with therapeutic gains or inferences being illusions caused by the primitive logic of association leading to an assumption of causation. Also, the field of neuroscience is barely mentioned. The author uses the term "Big Science" as a kind of pejorative epithet, alongside "Big Pharma", a kind of ad hominem style of argument which seems to suggest that research findings from "Big Science" must be biased, and that the lack of research findings which support her position must have to do with the scientists being inadequate, rather than her position in fact being weak. One piece of "Big Science"-style research she does cite, in support of psychoanalysis, is upon closer observation a single study, with no adequate control group, little critical review. Yet she seems to aggrandize these findings in a way similar to how I have seen "Big Pharma" reps market medications based on a single, fairly weak research study.

The strength of this book lies in the biographical stories of suffering individuals, and of the descriptions of how people attempted to help them. Some of the most effective strategies are clearly based on common sense: humane social and community support, minimizing iatrogenic harm, promotion of the greatest degree of freedom possible. She argues effectively that Freudian ideas were quite liberating, permitting discussion of subjects previously held under a veil of taboo in the Victorian era, such as the nature of sexual drives. Also, these Freudian notions tended not to pathologize the drives themselves, but rather considered the drives to be innately normal, hence inviting frank, uncensored dialog as a pathway to greater freedom. The book highlights, importantly, some of harms done to people by misguided therapists and theories. And the book highlights the fact that symptoms generated by the mind can present in different ways, according to cultural influences. She argues that classification schemes can follow a fashion, and that ailments may present to follow the classification scheme, rather than the other way around.

So, in conclusion, a book with some interesting biographical sketches of patients and therapists. And some good discussion about the dangers of over-medicalizing human nature. But she does not convey a good understanding of psychological or neuroscience research, and certainly does not lay out evidence in a balanced or comprehensive way.

Thursday, February 11, 2010

Olympics & Psychiatry


The Olympic games cost billions of dollars to prepare for, and to host. Therefore, it has been a subject of controversy, particularly because so many people (both globally, and in the local communities near the Olympic sites) are suffering with homelessness, poverty, lack of opportunities for therapy, education, recreation, healthy community, etc. There is understandable criticism that those billions could have been better spent addressing these serious social problems directly.

A few things in particular bother me about the Olympics: one main corporate sponsor is a soft-drink company; another is a fast food company. These companies, in my opinion, contribute to the health problems of millions of people. It is like having cigarette companies as sponsors. The Olympic torch was preceded by a truck with neon lights and dancers boisterously advertising soft drinks...I think this was contrary to the spirit of the event--certainly in bad taste-- and I hope future Olympic organizers can be more health-conscious in considering whom to allow as corporate sponsors.

Overall, however, my opinion is that the Olympics are very healthy, for the following reasons:

1) In these games we have an opportunity for nations of the world to display a type of excellence, and to come together in serious, spirited, but friendly competition. It is a model of sublimating competitive conflict through sport or play, rather than through war. And it is an opportunity for multicultural celebration, in a setting which encourages sportsmanship, generosity, and hospitality.

2) The ethical problem of spending extravagantly while many do not have basic needs met is a very serious one. Here are a few ideas about this:
-Almost any activity could be considered extravagant spending (in terms of money, time, or attention) : much university education does not address the needs of impoverished, displaced, or other suffering individuals. Much in medicine (e.g. transplantation surgery) could be considered expensive extravagance, benefiting a small number of people while others have inadequate basic health care. A great deal of scientific exploration (e.g. the space program) is very expensive, yet doesn't help directly with poverty or world hunger. Investment of time, attention, or money in the arts (e.g. music, theatre, literature, visual arts) could be considered wasteful, since it does not directly help with poverty or homelessness. People could be directed to stop spending time reading novels, going to plays, going jogging, having pets, etc. because they should better be volunteering to assist with dire social problems.
-Regarding the above examples, I think most would agree that these "extravagant" aspects of human endeavour are healthy...it is part of human nature to strive for excellence and for new frontiers (whether this be in space travel, advanced surgery, mathematics, theatre, or sports): it is part of healthy civilization that we allow our attention, time, and money to be invested in these activities. It would induce a type of global psychosocial impoverishment to suppress these activities. The development of a culture which is advanced in terms of arts, sciences, and sports, and which shares its advances with other cultures, is healthy. While these activities may not directly help with social problems, they are part of building a healthier society, which in turn can address its social problems with greater ease and morale.

This social issue has a metaphorical parallel, I think, in individual cases of depression, anxiety, or other psychological symptoms: in a depressed or anxious state, a much greater portion of energy may be invested to meet basic needs. Energy itself may be in short supply, and it may require most of this energy just to prepare food, or to make it through the day. It makes sense to budget energy in such a way that few "extravagances" are allowed. Yet, if this budgeting practice persists for years, it may lead to a perpetuation of a grey, depressed status quo. "Extravagance" may be a necessary part of energy budgeting in depressive states--this extravagance might take the form of energy expenditures which may not seem affordable (e.g. exercising, taking up a new activity, involving oneself in a new community, socializing, taking time away from a hard-to-maintain work schedule in order to volunteer, etc.)---and indeed, such extravagances may sometimes not work out (e.g. efforts to socialize may fizzle, the new activity doesn't work out due to depressive fatigue, etc.). But allowing for extravagances is a type of balanced risk that can permit growth from a depressive status quo.

Suppose a room-mate invites a whole bunch of people to your home, for a lavish celebration. Suppose you are very opposed to this event, perhaps in the context of your room-mate not having done his share of chores regularly for the past 4 years (etc.) ...But suppose also that the guests are themselves honorable, noble people who come from many lands, who are polite, respectful, talented, and interesting. Perhaps in this context it is healthier to set aside one's differences, and to welcome the guests with a spirit of hospitality and celebration.

I think it is great to have the Olympics in Vancouver: I wish all the athletes and spectators a happy, healthy, spirited few weeks of enjoying our community, of enjoying vigorous competition and good sportsmanship. Afterwards, I hope that all of us in the community may enjoy the resources constructed for the games, and that special effort may be made to include those in greatest need.

Wednesday, February 10, 2010

Sleep, Hormones, and Obesity

Here are some excellent references about the interaction between sleep, hormones, and obesity. They were contributed by a reader (thank you very much!):


http://www.ncbi.nlm.nih.gov/pubmed/16459757

http://www.ncbi.nlm.nih.gov/pubmed/18591489


http://www.ncbi.nlm.nih.gov/pubmed/19056602

http://www.ncbi.nlm.nih.gov/pubmed/15531540

http://www.ncbi.nlm.nih.gov/pubmed/18564298

Lastly a good review paper and shows the basics (along with some fun diagrams)
http://www.jpp.krakow.pl/journal/archive/1205_s6/articles/01_article.html


Comments:

These references make it very clear that inadequate sleep increases the likelihood of obesity.

The last article was interesting, but oddly lacked any discussion of culture or psychology with respect to eating behaviours or obesity.

In terms of advising a fixed, early wake time, I believe this is entirely consistent with a plan to get adequate, optimal sleep. In fact, I believe that when individuals who are struggling with insomnia have a habit of sleeping in, the overall sleep quality diminishes, the insomnia pattern is exacerbated and perpetuated, and the health problems associated with inadequate sleep are likely to worsen.

Therefore, I believe that sleep quality and the restorative health benefits of sleep are most optimal if wake times are consistent and early. Possible exceptions to this could occur in adolescents, who probably need more sleep (but even then, it would be better for them to get that additional sleep by sleeping longer hours but getting up at the same time every day, rather than by sleeping in on weekends). Another exception could be in the setting of a physical illness, in which case one might need to stay in bed longer to recover.

Monday, February 1, 2010

Self-help books

There are a lot of self-help books to choose from, dealing with almost anything including mood problems, anger, anxiety, body image, obesity, shyness, relationship or marriage problems, etc.

There are others that might aim to help a person develop creativity, or guide one with respect to some other life pursuit, such as building a sense of purpose, meaning, balance, simplicity, etc.

I think it is worthwhile to familiarize yourself with the self-help literature. I think it can be something like getting a textbook for a course at school...while some textbooks may not be very well-written, I think having a textbook at all can at least allow some extra tangible structure in therapeutic work.

Most self-help books have exercises to work through, often requiring you to write things out with pen and paper. I think it is important to actually do the exercises, as opposed to just leafing through the book, or thinking that you've done all those things in your mind before anyway. Working through exercises strengthens the mind, even if the exercises themselves are not very well-constructed. It is something like working through arithmetic or grammar problems. Even if the exercises are boring or trite, the earnest effort spent working through them will strengthen your ability and insight about the subject matter. Also, most self-help books, even if they are poorly written, can act as structures to develop your own personalized insights about the subject matter--the workbooks can be a frame to do the work, as opposed to being an intrinsic source of insight.

Many self-help books are organized with cognitive-behavioural ideas in mind. Once again, even if you don't care much for cognitive therapy, the exercises remain useful, provided you engage in them earnestly (it is possible to do these exercises in a half-hearted or sarcastic way, etc. -- which would minimize any possible benefit, just as with any other exercise in life).

What does evidence have to say about self-help books? So-called "bibliotherapy" (yes, someone had to designate an awkward piece of vocabulary to describe "reading") has an evidence base--here are a few references:

Gregory et al. published this 2006 meta-analysis showing cognitive bibliotherapy was effective for depression: Professional Psychology: Research and Practice 2004, Vol. 35, No. 3, 275–280. They concluded that bibliotherapy had an effect size of about 0.77, which is substantial, and comparable to effect sizes from medications and psychotherapy.

Here is a reference to a 2003 meta-analysis by Newman et al. showing that bibliotherapy was effective in the treatment of various anxiety disorders:
http://www.ncbi.nlm.nih.gov/pubmed/12579544

Here is a 2004 reference showing that guided self-help is effective in treating bulimia:
http://www.ncbi.nlm.nih.gov/pubmed/15101068

In conclusion, I do strongly recommend working through self-help books. I find that it can be important to look at several different ones, as there can be style or content differences causing you to prefer one over the other.

The main word of caution I have about self-help is that some authors may have a very biased point of view (perhaps influenced by dogmatic or eccentric beliefs regarding politics, religion, health care, etc.), and may therefore lead a vulnerable individual towards an unhelpful set of beliefs or actions.

So my main recommendation is for standard cognitive-therapy style self-help, as a place to get started. There need not be any bias in cognitive therapy, since it is merely a neutral frame for your own therapeutic work.

Thursday, January 21, 2010

Rating Scales: limitations & ideas for change

A visitor's comment from one of my previous posts reminded me of an issue I'd thought about before.

In mental health research, symptom scales are often used to measure therapeutic improvement. In depression, the most common scales are the Hamilton Depression Rating Scale (HDRS), the Montgomery-Ashberg Depression Rating Scale (MADRS), or sometimes the Beck Depression Inventory (BDI). The first two examples involve an interviewer assigning a score to a variety of different symptoms or signs. The last example is a scale which is filled out by a patient.

Here are examples of questions from the HDRS, with associated ranges of scoring:
depressed mood (0-4); decreased work & activities (0-4); social withdrawal (0-4); sexual symptoms (0-2); GI symptoms (0-2); weight loss (0-2); weight gain (0-2); appetite increase (0-3); increased eating (0-3); carbohydrate craving (0-3); insomnia (0-6); hypersomnia (0-4); general somatic symptoms (0-2); fatigue (0-4); guilt (0-4); suicidal thoughts/behaviours (0-4); psychological manifestations of anxiety (0-4); somatic manifestations of anxiety (0-4); hypochondriasis (0-4); insight (0-2); motor slowing (0-4); agitation (0-4); diurnal variation (0-2); reverse diurnal variation (0-3); depersonalization (0-4); paranoia (0-3); OCD symptoms (0-2)

One can see from this list that depressive syndromes which have many physical manifestations will obviously score much higher. The highest possible score on the 29-item HDRS is 89. It is likely that physical manifestations of acute depression resolve more quickly, particularly in response to medications. Therefore, the finding that more severe depressions have better response to medication could be simply an artifact of the fact that physical symptoms respond better and more quickly to physical treatments.

A person who is eating and sleeping poorly, is tired, feels and looks physically ill, who is not working, who is not seeing friends as much, and whose symptoms fluctuate in the day, would already get an HDRS score of up to 30 -- without actually feeling depressed or anxious at all! A person feeling very depressed, struggling through life with little pleasure, meaning, satisfaction, or joy -- but sleeping ok, eating ok, and forcing self through daily routines such as work, social relationships, etc. -- might only get a score of 4-6 on this scale.

I acknowledge that the many questions on the HDRS cover a variety of important symptom areas, and improvement in any one of these domains can be very significant.

But -- a big problem of the scale, for me, is that the relative significance of the different symptoms is arbitrarily fixed by the structure of the questionnaire. So, for example, are the 4 points for fatigue of equivalent importance to the 4 points for guilt, or social withdrawal, or depressed mood? Would different individuals rate the relative importance of these symptoms differently? Maybe some people might prefer to sleep better, rather than socialize with greater ease. Also, perhaps some of the symptom questions deserve to be "non-linear," or context-dependent. So, for example, perhaps mild or intermittent depressed mood might deserve a score of only "1". Moderately depressed mood might warrant a score of "5". Severe depressive mood might warrant a score of "20". Or, relentless moderate symptoms over a period of years might warrant a score of "20", while only short-term or episodic moderate symptoms might warrant a score of "5".

It would be interesting to change the weighting of these symptom scores, on an individualized basis.

Also, it would be interesting to see the results of depression treatment studies portrayed with all the separate symptom categories broken down (i.e. to see how the treatment changed each item on the HDRS). Many researchers or statisticians would complain that to portray, or make conclusions, about so many results at once, would reduce the statistical significance. Statistically, a so-called "Bonferroni correction" is necessary if multiple hypotheses are being made simultaneously: if n hypotheses are made, the statistical significance is reduced by a factor of 1/n. Based on this statistical idea, most researchers prefer to analyze just a single quantity, such as the HDRS score, instead of looking at each component of the score separately.

But, this analysis dilutes the data from any study, in the same way that the analysis of artworks in a museum would be diluted if each piece were summarized only by its mass or area.

A more complete analysis would portray every category at once. A graphical presentation would be reasonable, perhaps taking the form of a 3-d surface (once again). The x-axis could represent the different symptom areas (or scores on each item on the HDRS); the y-axis could represent time; and the z-axis could represent the severity. With this analysis, we could say that we are not actually making n hypotheses--we are making a single hypothesis, that the multifactorial pattern of symptom results, manifest as a 3-d surface, is changing over time. Each individual patient's symptom changes, in every symptom category, could be represented on the graph. In this way, no data, or analytic possibility, would be lost or diluted. The reader would be able to inspect every part of the data from the study, and perhaps notice interesting relationships which the original researchers had not considered.

Some patterns of change with different treatment could present in the following ways, as shown in such as 3-d surface:
1) some symptoms improve dramatically with time, while others are much slower to change, or don't change at all. In depression treatment studies, sleep or appetite might change very quickly with a potent antihistaminic drug...this would immediately lead to pronounced improvement on the overall HDRS score, but might not be associated with any significant improvement in mood, energy, concentration, etc.
2) some symptoms might improve immediately, but deteriorate right back to baseline or worse after a few weeks or months. Benzodiazepine treatment would produce such as pattern, in terms of sleep or anxiety improvement. A medication which is sedating but addictive might cause rapid HDRS improvement, but only a careful look at individual category changes over a long period of time would allow us to see the addiction/tolerance pattern. Some people drink alcohol to treat their anxiety symptoms -- such a behaviour might rapidly improve their HDRS scores! But of course, the scores would return to worse than baseline within a few weeks or months. And the person would probably have new symptoms and problems on top of their original ones. So, we must be cautious about getting too excited about claims of rapid HDRS change!
3) some treatments might cause a global change in most or all symptoms...this would be the goal of most treatment strategies. Such a pattern would imply that the multi-symptom syndrome (in this case, the "major depressive disorder" construct) is in fact valid, all components of which improving together with a single treatment.
4) some combined treatments might work well together...for example, a treatment which helps substantially with energy or concentration (such as a stimulant), together with a treatment which helps with mood, socialization, optimism, or anxiety (such as psychotherapy, or an antidepressant). These treatments on their own might appear to be equivalent if only the total HDRS score is considered (since each would reduce symptom points overall); the synergistic effect would only be apparent by looking at each symptom domain separately.

Finally, I think it is important to look at very broad, simple indicators of quality of life, or of general improvement. The "CGI" scale is one example, although it is awkward and imprecise in design, and most likely prone to bias.

Quality of life scales are important as well, in my opinion, since they look at overall satisfaction with life, rather than merely a collection of symptoms.

In practice, only a discussion with the person receiving the treatment can really assess whether it is worthwhile to continue the treatment or not. In such a discussion, the subjective pros and cons of the treatment can be weighed. Even if the treatment has had a minimal impact on a rating score, it might be subjectively beneficial to the person receiving it. And even if the treatment has produced large rating score changes, it might not be the person's preference to continue. I suppose the role of a prescriber is mainly to facilitate such a dialog, and contradict the patient's wishes only if the treatment is objectively causing harm.

Health benefits of dietary nut intake


Dietary nut intake is strongly associated with a variety of health benefits, particularly a lower risk of developing cardiovascular disease. Here is a link to a recent review of the subject:
http://www.ncbi.nlm.nih.gov/pubmed/19321572

This 2009 article describes a carefully controlled, inpatient, 4-day randomized study in which subjects were given a breakfast containing walnuts; or a "placebo" breakfast containing the same number of calories, and the same amount of carbs & fat, but no walnuts. The results showed that a breakfast containing walnuts leads to a significantly greater feeling of satiation (contentment and satisfaction with respect to food), at lunchtime:
http://www.ncbi.nlm.nih.gov/pubmed/19910942

Therefore, eating walnuts, as part of a balanced diet, is likely to maintain a feeling of satiation, and therefore reduce some of the physiological drives which can contribute to unhealthy eating behaviours.

This is a reference to a large prospective study of over 50 000 women followed over 8 years. The results included a multivariate analysis controlling for many other factors, such as physical activity, smoking, other dietary habits, etc. There was a slight reduction in weight gain or obesity in those who included more nuts in their diet, and in fact the more frequent the nut intake, the lower the risk of obesity:
http://www.ncbi.nlm.nih.gov/pubmed/19403639

With respect to mental health, I think that a balanced, healthy diet is important. Lifestyle habits, including nutritional choices, which reduce risk of cardiovascular disease, are likely also to reduce risk of degenerative brain disease. Walnuts are a source of omega-3 fatty acids, for which there is modest evidence of beneficial effects on mood.

Treatment of eating disorders requires deliberate attention to healthy, regular nutritional habits. Many individuals with eating disorders exclude certain types of food from their diets, based on an unfounded belief that the exclusion would lead to improved control of appetite or caloric intake.

Nuts in particular clearly deserve to be part of a healthy diet, unless there are issues such as food allergy.

Wednesday, January 13, 2010

Antidepressants only effective in severest depression?

A recent article in JAMA by Fournier et al. is a meta-analysis of antidepressant treatment effects assessed in relation to depression severity. Here's the reference:
http://www.ncbi.nlm.nih.gov/pubmed/20051569

The results show that antidepressants work significantly well, compared to placebo, only for very severe depression (corresponding to Hamilton Depression Rating Scale scores of at least 25).

The analysis is quite well-done, and the results are also presented in a graphical form clearly showing a linear increase in antidepressant effect as baseline depression scores increase.

The authors observe that antidepressants are most commonly prescribed to people who have milder depressions--a population in which they show that medications arguably do not work.

Here are a few of my criticisms of this study:

1) the duration of each trial included in the meta-analysis was between 6 and 11 weeks. In my opinion, depressive disorders are long-term, highly recurrent problems, which have a natural period over at least 6-11 months, not 6-11 weeks. Treatments to address mood disorders of any severity require much longer durations. The short duration could cause a significant under-estimation of treatment effects.

2) the study, like many, looks at "depression alone." In most real-life situations, outside of a research study, individuals have several different problems, such as mild depression + social anxiety, or mild depression + panic attacks, etc. The presence of other symptoms, particularly anxiety symptoms, most likely would increase the likelihood of antidepressants helping.

3) Milder depressions, just like more severe depressions, may actually improve more consistently with a "second step" such as combination with psychotherapy, or combining two different antidepressants. The mildness of a medical syndrome does not necessarily mean that the effective treatments need only to be "mild."

4) Milder depressive syndromes may be more prone to misdiagnosis.

5) current "resolution" to measure treatment effects in depression is quite poor. "Depression" is a very broad category. An analogy could be considering "abdominal pain" to be a diagnostic category. If "abdominal pain" is the only category, and is simply rated on a severity scale (rather than subcategorized to obtain a precise diagnosis), and the treatment offered for "abdominal pain" is appendectomy, then we would probably see no difference in treatment effectiveness between appendectomy and placebo. This is because appendectomy is only effective to treat appendicitis (a subset of the abdominal pain population), and is either ineffective or harmful in treating abdominal pain patients without appendicitis (except, perhaps, for those patients who have a placebo improvement of psychosomatic or factitious abdominal pain, an improvement which they attribute to having surgery).

We currently do not have the science to subcategorize depression in a more clinically meaningful way (there are subcategorization schemes, but they don't have much relevance in terms of treatment).

But we do have a research method which could improve "resolution":
-instead of comparing two populations of depressed individuals, one group receiving antidepressant (or some other treatment), and the other receiving placebo (or some other alternative), the study design could instead be to offer every individual courses of placebo, alternating with antidepressant (or "treatment one" alternating with "treatment two"). Each course of treatment would have to last an adequate length of time. The analysis would aim to show whether there is a subset of individuals who respond to the antidepressant, or a subset of individuals who do better with placebo. The averaged results over the whole group might show that antidepressant effects do not differ from placebo (just like appendectomy might not differ from placebo in treating "abdominal pain"), but the individualized result could show that some individuals improve substantially with the antidepressant (just like appendectomy would save the lives of the small group of "abdominal pain" patients who have appendicitis).

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In the meantime, though, I think it is reasonable to recognize that antidepressants are less consistently helpful when symptoms are less severe.

Wednesday, January 6, 2010

A Gene-Environment-Phenotype Surface


I've been thinking of a way to describe the interaction between genes, environment, and phenotype qualitatively as a mathematical surface.

In this model, the x-axis would represent the range of genetic variation relevant to a given trait. If it was a single gene, the x-axis could represent all existing gene variants in the population. Or, the idea could be extended such that the x-axis could represent all possible variants of the gene (including the absence of the gene, represented as "negative infinity" on the x-axis). The middle of the x-axis (x=0) would represent the average expression of the relevant gene in the population.

The y-axis would represent the range of environmental variation relevant to a given trait. y=0 would represent the average environmental history in the population. y="negative infinity" would represent the most extreme possible environmental adversity. y="positive infinity" would represent the most extreme possible environmental enrichment.

The z-axis would represent the phenotype. For example, it could represent height, IQ, extroversion, conscientiousness, etc.

In my opinion, current expressions of "heritability" represent something like the partial derivative dz/dx at x=0 and y=0; or perhaps, since the calculation is based on a population sample, heritability would be the average of derivatives dz/dx over various sampled (x,y) points near x=0 and y=0.

Conventional heritability calculations give a severely limited portrait of the role of genes on phenotype, since it condenses the information from what is really a 3-dimensional surface into a single number (the heritability). This is like looking at a sculpture, then being told that the sculpture can be represented by a single number such as "0.6", based on the average tilt on the top centre of the artwork.

A more comprehensive idea of heritability would be to consider that it is the gradient, a component of which is dz/dx. This gradient would not be a fixed quantity, but could be considered a function of x and y.

It is particularly interesting to me to consider other properties of this surface, such as what is the derivative dz/dy at different values of y and x? This would determine the ease with which environmental change could change a phenotype regardless of genotype.

A variety of different shapes for this surface could occur:

1) z could plateau (asymptotically) as y approaches infinity. This implies that the phenotype could not be changed beyond a certain point, regardless of the degree of environmental enrichment.
2) z could appear to plateau as y increases, but this is only because we do not yet have existing environments y>p, where p is the best current enriched environment. It may be that z could increase substantially at some point y>j, where j>p. I believe this is the case for most medical and psychiatric problems. It implies that we must develop better environments. Furthermore, it may be that for some genotypes (values of x), z plateaus as y increases, but for other genotypes z changes more dynamically. This implies that some people may inherit greater or lesser sensitivity to environmental change.
3) dz/dx could be very high near the origin (x,y)=(0,0), leading to a high conventional estimate of heritability; but at different values of (x,y), dz/dx could be much smaller. Therefore, it may be that for some individual genomes or environmental histories, genetic effects may be much less relevant, despite what appears to be "high heritability" in a trait.
4) dz/dx could be very low near the origin, but much higher at other values of (x,y). Therefore, despite conventional calculations of heritability being low, there could be substantial genetic effects on phenotype for individuals with genotypes or environmental histories which are farther from the population mean.

The idea of x itself being fixed in an individual may also not be entirely accurate, since we now know of epigenetic effects. Also, evolving technology may allow us to change x therapeutically.

In order to describe such a "surface", many more data points would need to be analyzed, and some of these might be impossible to obtain in the current population.

But I think this idea might qualitatively improve our understanding of gene-environment interaction, in ways that could have practical applications (current heritability estimates are typically 0.5 for almost anything you can think of--this fact seems intuitively obvious, but is not very helpful to inspire therapy or change, can sometimes increase a person's sense of resignation about the possibility of therapeutic change, and can distort understanding about the relative impacts of genes and non-genetic environment).