Tuesday, May 31, 2011

Is it unusual to have 165 papers in one journal?

How about if you've been Editor-in-Chief of the journal for the past 15 years?

Hagop Akiskal, M.D is Professor of Psychiatry and Director of International Mood Center San Diego Veterans Administration Medical Center. Since 1996, he has been the Editor-in-Chief of the Journal of Affective Disorders. He is indeed a coauthor on 165 papers appearing in that journal (see image below). Out of 403 papers that come up in a PubMed search for 'Akiskal H', 162 of them are in JAD. Should this be considered self-publishing? Highly unethical? Or par for the course?

To be fair:

click on image for a larger view

Viewing all 165 titles from the original ScienceDirect search, we can see two major themes emerge: bipolar (157 articles) and temperament (133 articles). As I mentioned in my previous post on Abusing Chocolate and Bipolar Diagnoses, the senior author of the 'Are "social drugs" (tobacco, coffee and chocolate) related to the bipolar spectrum?' paper (i.e., Hagop Asiskal) has a goal of expanding the diagnosis of bipolar disorder into the "bipolar spectrum".

More on this in a future post.

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Thursday, May 26, 2011

Abusing Chocolate and Bipolar Diagnoses

Is chocolate a legal "social drug" of abuse in the same category as nicotine, caffeine, and alcohol? Do you hang out at chocolate cafes with the purpose of becoming high or intoxicated? No? Have you heard of cancer-related deaths due to chocolate or driving under the influence of chocolate?

And really, how much chocolate is considered "chocolate abuse"?1

A new paper by Maremmani et al. (2011) addressed none of these questions, but asked 562 depressed Italian outpatients about their cigarette, coffee, and chocolate consumption. Why? Actually, it's not clear.
Across all ages and cultures, mankind has always used substances in order to induce pleasurable sensations or desirable psychophysiological states. These substances, notably caffeine, tobacco, alcohol and chocolate, given their widely accepted recreational use, can be labeled ‘social drugs’.
This passage appeared as Background in the Abstract and as the first two sentences of the Introduction: brief literature review. But we have no explanation of why cigarettes, coffee, and chocolate are assumed to be "social drugs". Are there no solitary smokers, drinkers, and eaters? Look at the large number of singletons staring at laptop screens at any Starbucks. However, cafe culture in Italy or France does allow for smoking, espresso sipping, and chocolate croissant nibbling all at the same time. Also, anti-smoking laws in other countries force smokers to congregate outside to smoke, which often turns into a social activity.

But why look at the consumption of "social drugs" in people who are depressed? Aren't these individuals less inclined to be social? And aren't they likely to show anhedonia (loss of interest of pleasure) according to DSM IV criteria?
2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)
We're reminded that caffeine improves mood and cognitive performance, increases mental energy, and reduces fatigue, that nicotine increases attention and working memory, and that chocolate can also improve mood and even reduce stress. We're also reminded that psychiatric patients use more drugs than those in the general population:
With regard to caffeine, in hospitalized psychiatric patients the prevalence of tolerance and intoxication is significantly higher than in the healthy population. The highest caffeine intake has been found in patients suffering from eating disorders (Ciapparelli et al., 2010) and schizophrenia (Rihs et al., 1996), the lowest in patients with anxiety disorders and major depression (Ciapparelli et al., 2010; Rihs et al., 1996).
It's well known that the prevalence of smoking among individuals with schizophrenia is quite high (70-80%), higher than for those with other mental illnesses (Winterer, 2010). In fact, smoking is often considered a form of self-medication. So are cigarettes a "social drug" for smokers with schizophrenia?

Finally, we have the case of chocolate, where Maremmani et al. (2011) issue a number of curious pronouncements:
Lastly, the consumption of chocolate has shown interesting forms of linkage with psychiatric conditions. The correlation most often studied is that with depression: it has been observed that the craving for the rewards given by chocolate intensifies when depressive mood is induced... More severe depressive symptoms have been associated with higher chocolate consumption (Rose et al., 2010). Self-labeled ‘chocolate addicts’ do not generally seem to suffer from eating disorders, but may constitute a population of psychologically vulnerable people with a high predisposition to depression and anxiety disorders (Dallard et al., 2001). More specifically, a craving for chocolate seems to be unusually high not only in cases of depressed mood, but also in conditions of emotional dysregulation, like anxious and irritable states. The capacity to find comfort in eating chocolate seems to be related to the biological mechanisms of emotional instability,2 so that the depression associated with a craving for chocolate turns out to be an efficient discriminator of hysteroid dysphoria3 and DSM-IV atypical depression (Parker and Crawford, 2007; Schuman et al., 1987).
So of the three "social drugs", chocolate seems like the winner among depressives of any sort, especially those with the greatest emotional dysregulation (i.e., those with bipolar disorder).

Then the introductory narrative inserts a non sequitur or three on illegal drugs of abuse (heroin and cocaine) and alcohol use in bipolar disorder, and "cyclothymic traits" in bipolar individuals, heroin addicts, and alcoholics. Furthermore........
This reported bipolar connection, in our opinion, is not just valid at a clinical level. We have stressed the possible role of the bipolar spectrum in the pathogenesis of substance use disorders. In particular, our integrated model provides an explanation for why the bipolar spectrum is the psychic substrate for the development of a substance-resorting attitude...
So let's blur the lines between alcoholics and coffee drinkers, schizophrenic smokers and chocolate-craving dysthymics, severe bipolar I disorder and mild cyclothymia, shall we? Then what?

The 562 depressed Italian outpatients were initially given one of four DSM-IV-TR diagnoses:
192 patients with a Major Depressive Episode, 212 with Major Depression, Recurrent, 119 with Bipolar Depression, and 39 with Depression NOS (“not otherwise specified”).
The participants also filled out the Hypomania Checklist (HCL-32) and according to the dichotomous rating procedure, there were 306 non-bipolar and 256 bipolar depressive patients [vs. 119 bipolar depressives according to DSM-IV-TR]. This illustrates the expansionism of the "bipolar spectrum" project, which is a major goal of the senior author.

Then we have the vague quantification of chocolate use:
The social drug habit was recorded in terms of the use of tobacco, coffee and dark chocolate-based food (chocolate bars, hot chocolate, chocolate-containing ice cream, biscuits or cakes). We classified smoking habits by division into 3 ascending ranks: total non-smokers, past regular users and current regular users and considered one cigarette as a “unit”. As to coffee, we distinguished between regular consumption (at least one coffee a day) and sporadic or no use [one cup was considered a unit].
What was considered a chocolate "unit"? The paper doesn't say.

To reiterate: the goals of the study were to prove that the notion of "bipolar" should be expanded, and that those on the "bipolar spectrum" are more likely to abuse substances of any sort.

And did the results support these ideas? Well, 44.5% of the DSM-IV-TR bipolar depressives were current smokers, and 43.4% of the HCL-32 bipolar depressives were current smokers. However, the statistics were only significant in the latter case, because the comparison was between only two groups, instead of between four groups. Even better are the number of cigarettes smoked daily: 10.66 for the DSM bipolars [vs. 8.13 for the other groups combined], and 10.45 for the HCL bipolars [vs. 7.51 for the non-bipolars]. The stats were nonsignificant in the first case (p=.33) and highly significant in the second case (p=.0003).

In contrast, there were no differences in chocolate consumption no matter how you divided the groups, which did not seem to disturb the authors. After touting the psychotropic properties of chocolate in the Introduction, they concluded:
It should be noted at this point that the result for chocolate should not necessarily be regarded as contradictory with the findings for coffee and cigarette use; the fact is that regular chocolate eaters appear to crave for chocolate to enjoy its taste, without paying any special attention to its potential psychotropic properties...

Time for a box of Ghost Chili Salted Caramels!


1 "I'd go with a pound a day and you've got a problem."

2 So we all know a lot of unstable people, then...

3 Which is not the same as PMS, of course...


Maremmani I, Perugi G, Rovai L, Maremmani AG, Pacini M, Canonico PL, Carbonato P, Mencacci C, Muscettola G, Pani L, Torta R, Vampini C, & Akiskal HS (2011). Are "social drugs" (tobacco, coffee and chocolate) related to the bipolar spectrum? Journal of affective disorders PMID: 21605911

Winterer G. (2010). Why do patients with schizophrenia smoke? Curr Opin Psychiatry 23:112-9.

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Wednesday, May 18, 2011

Improving the Physical Health of People With Serious Mental Illness

Mental Health Blog Party Badge

Today is the Mental Health Blog Party sponsored by the American Psychological Association as part of Mental Health Month. A widely neglected part of mental health treatment is encouraging and maintaining good physical health. This is extremely difficult when some of the major drugs prescribed for serious mental illnesses (such as schizophrenia and bipolar disorder) produce substantial weight gain. The "second generation" or atypical antipsychotics can cause obesity and hence diabetes, hypertension, cardiovascular problems, high cholesterol, and stroke.

Yesterday the BBC posted this headline:
Mentally ill have reduced life expectancy, study finds

By Dominic Hughes Health correspondent, BBC News

People suffering from serious mental illnesses like schizophrenia or bipolar disorder can have a life expectancy 10 to 15 years lower than the UK average.

Researchers tracked the lives of more than 30,000 patients through the use of electronic medical records.

They found that many were dying early from heart attack, stroke and cancer rather than suicide or violence.

Mental health groups say vulnerable people need to be offered better care to prevent premature deaths.

. . .

"We need to improve the general health of people suffering from mental disorders by making sure they have access to healthcare of the same standard, quality and range as other people, and by developing effective screening programmes."
The BBC article referred to a paper that was published today in PLoS ONE (Chang et al., 2011). The authors reviewed the electronic database of a major mental health care provider (the South London and Maudsley NHS Foundation Trust). The results were alarming (but not new, unfortunately):
A total of 31,719 eligible people, aged 15 years or older, with SMI [serious mental illness] were analyzed. Among them, 1,370 died during 2007–09. Compared to national figures, all disorders were associated with substantially lower life expectancy: 8.0 to 14.6 life years lost for men and 9.8 to 17.5 life years lost for women. Highest reductions were found for men with schizophrenia (14.6 years lost) and women with schizoaffective disorders (17.5 years lost).

click on image for a larger view

Figure 1 (Chang et al., 2011). Annual mortality risk (%) by age groups and diagnoses of mental illness, compared to England and Wales population in 2008.

The figure above illustrates the 2008 population of England and Wales in the red bars for five different age group: 15-29, 30-44, 45-59, 60-74, and 75+. Those with substance use disorders are shown in maroon, schizoaffective disorder in green, bipolar disorder in purple, schizophrenia in aqua, and depression/recurrent depression in light brown.

Mortality risk is increased for all psychiatric diagnoses, and is especially evident in the middle three age groups. Life expectancies were estimated using these data, and the results
confirmed substantially shortened life expectancies at birth for all serious mental disorder groups investigated compared to national norms. Largest reductions were found for men with schizophrenia, women with schizoaffective disorders, and both men and women with substance use disorders.

Why might this be? The authors do not speculate beyond stating that the "underlying causes may be multiple." Certainly, one can imagine that medication-induced weight gain [and increased levels of smoking] among the SMI contributes to lowered life expectancies.

To counteract these dismal statistics, a regular part of mental health treatment should include programs that promote better physical health. Smoking cessation and nutritionists and structured exercise classes in addition to standard psychiatric care and substance abuse treatment.

A six month intervention pilot study in Maryland enrolled 63 overweight participants at psychiatric rehabilitation day programs (Daumit et al., 2010):
Results: ... In total, 52 (82%) completed the study; others were discharged from psychiatric centers before completion of the study. Average attendance across all weight management sessions was 70% (87% on days participants attended the center) and 59% for physical activity classes (74% on days participants attended the center). From a baseline mean of 210.9lbs (s.d. 43.9), average weight loss for 52 participants was 4.5lb (s.d. 12.8) (P<0.014). On average, participants lost 1.9% of body weight. Mean waist circumference change was 3.1cm (s.d. 5.6). Participants on average increased the distance on the 6-minute walk test by 8%.

Conclusion: This pilot study documents the feasibility and preliminary efficacy of a behavioral weight-loss intervention in adults with serious mental illness who were attendees at psychiatric rehabilitation centers...
Although a 2% loss of body weight may not seem like much, it's better than a 10% weight gain over the same time period. The medical profession is obligated to provide the means for improved physical health in persons with serious mental illnesses. When physical health is potentially compromised by psychiatric treatments such as atypical antipsychotics, action to improve the situation is even more urgent.


Chang, C., Hayes, R., Perera, G., Broadbent, M., Fernandes, A., Lee, W., Hotopf, M., & Stewart, R. (2011). Life Expectancy at Birth for People with Serious Mental Illness and Other Major Disorders from a Secondary Mental Health Care Case Register in London PLoS ONE, 6 (5) DOI: 10.1371/journal.pone.0019590

Daumit, G., Dalcin, A., Jerome, G., Young, D., Charleston, J., Crum, R., Anthony, C., Hayes, J., McCarron, P., Khaykin, E., & Appel, L. (2010). A behavioral weight-loss intervention for persons with serious mental illness in psychiatric rehabilitation centers International Journal of Obesity DOI: 10.1038/ijo.2010.224

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Monday, May 16, 2011

Commendable Press Release from WUSTL

Figure from (Pergadia et al., 2011). Click on image for a larger view.

One of the more measured and accurate press releases I've seen in a while was issued by Washington University in St. Louis (WUSTL) to announce the publication of a paper (Pergadia et al., 2011) in the American Journal of Psychiatry:
Researchers Identify DNA Region Linked to Depression

ScienceDaily (May 15, 2011) — Researchers at Washington University School of Medicine in St. Louis and King's College London have independently identified DNA on chromosome 3 that appears to be related to depression.
The independent companion paper from Kings College appeared at the same time in AJP (Breen et al., 2011). The press release continues:
"What's remarkable is that both groups found exactly the same region in two separate studies," says senior investigator Pamela A. F. Madden, PhD, professor of psychiatry at Washington University. "We were working independently and not collaborating on any level, but as we looked for ways to replicate our findings, the group in London contacted us to say, 'We have the same linkage peak, and it's significant.'"
And next we have cautious statement warning us that this isn't "the depression gene." Particularly measured, in my view, is the caveat that a cure for depression isn't imminent:
Madden and the other researchers believe it is likely that many genes are involved in depression. While the new findings won't benefit patients immediately, the discovery is an important step toward understanding what may be happening at the genetic and molecular levels, she says.
This is quite different from Irresponsible Press Release Gives False Hope to People With Tourette's, OCD, and Schizophrenia, which claimed that a single unit recording study in two monkeys trained to perform a visual target discrimination task (Lennert & Martinez-Trujillo, 2011) "has brought new hope to these patients."

Instead, it's explained that the WUSTL and King's College researchers haven't even identified a specific gene:
From two different data sets, gathered for different purposes and studied in different ways, the research teams found what is known as a linkage peak on chromosome 3. That means that the depressed siblings in the families in both studies carried many of the same genetic variations in that particular DNA region.

Unlike many genetic findings, this particular DNA region has genome-wide significance. Often when researchers correct statistically for looking across the entire genome, what appeared originally to be significant becomes much less so. That was not the case with these studies.

Although neither team has isolated a gene, or genes, that may contribute to depression risk, the linkage peak is located on a part of the chromosome known to house the metabotropic glutamate receptor 7 gene (GRM7). Some other investigators have found suggestive associations between parts of GRM7 and major depression.
The press release ends on an exciting yet cautious note:
"The findings are groundbreaking," says McGuffin, senior author of that study. "However, they still only account for a small proportion of the genetic risk for depression. More and larger studies will be required to find the other parts of the genome involved."

Kudos to Jim Dryden, Associate Director of Broadcast Services.


G. Breen, B. T. Webb, A. W. Butler, E. J. C. G. van den Oord, F. Tozzi, et al. A Genome-Wide Significant Linkage for Severe Depression on Chromosome 3: The Depression Network Study. American Journal of Psychiatry, 2011; DOI: 10.1176/appi.ajp.2011.10091342

Lennert, T., & Martinez-Trujillo, J. (2011). Strength of Response Suppression to Distracter Stimuli Determines Attentional-Filtering Performance in Primate Prefrontal Neurons Neuron, 70 (1), 141-152 DOI: 10.1016/j.neuron.2011.02.041

M. L. Pergadia, A. L. Glowinski, N. R. Wray, A. Agrawal, S. F. Saccone, et al. A 3p26-3p25 Genetic Linkage Finding for DSM-IV Major Depression in Heavy Smoking Families. American Journal of Psychiatry, 2011; DOI: 10.1176/appi.ajp.2011.10091319

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Wednesday, May 11, 2011

Revisiting Depression's Cognitive Downside

Depression, by h.koppdelaney

Is depression actually good for you?

Experts now believe that mild to moderate depression may be good for us – and even help us live longer. Rebecca Hardy explains how to reap the benefits

We constantly hear how depression is blighting our lives, but some experts have an interesting, if controversial, theory: depression can be "good for us", or at least a force for good in our lives.

Is this the start of a new Negative Psychology1 movement? Let's all seek out personal tragedy, sadness, insomnia, and a profound sense of failure and hopelessness, because it's good for us!!

Last year, author and blogger Jonah Lehrer had a lengthy (and controversial) essay in the New York Times Magazine on Depression's Upside. The main idea, that depression has cognitive and evolutionary advantages, was largely based on a review paper by Andrews and Thomson (2009). In it, they put forth the analytical rumination hypothesis: depression is an evolved response to complex problems, and focusing on them to the exclusion of everything else is beneficial.

In response, The Neurocritic was motivated to write about Depression's Cognitive Downside:
On the contrary, numerous papers have shown that impairments in cognitive processes such as executive control, attention, and memory persist after a depressed person has recovered (Andersson et al., 2010; Baune et al., 2010; Hammar et al., 2009). In actively depressed patients, Baune and colleagues (2010) found impairments in all domains tested: immediate memory, visuospatial construction, language, attention, and delayed memory. These deficits can contribute to lower social and occupational functioning and a diminished quality of life. In addition, depression can be associated with declines in problem solving abilities on neuropsychological tests such as the Wisconsin Card Sorting Test and the Tower of London test.
Now, a new paper by von Helversen et al. (2011) has claimed that depression is good for decision making. Lehrer wrote about this study as support for the analytical rumination hypothesis in Does Depression Help Us Think Better?
Here’s where things get interesting: depressed patients approximated the optimal strategy [for hiring the best applicant in a simulated job search] much more closely than non-depressed participants did. The main problem with healthy subjects is that they proved lazy, unwilling to search through enough applicants. Those with depression, on the other hand, were much more willing to keep on considering alternatives, which is why they performed far better on the task. While this study comes with many caveats, it remains an interesting demonstration that depression, at least in specific situations, seems to enhance our analytical skills, making us better at focusing on social dilemmas.

Participants in the study were 37 inpatients diagnosed with major depression upon admission to the hospital (10 of whom were omitted "due to technical difficulties with the choice task"). The 27 remaining patients were classified as either "depressed" (n=15) or "recovered" (n=12) based on improved scores on the Patient Health Questionnaire (PHQ-D) between admission and testing (which was a mean of 6.25 days -- that seems like an incredibly rapid remission, which makes one wonder about the actual severity and why they were admitted in the first place). Only half of the patients, both depressed and recovered, were on antidepressants (none were on other medications), which seems unusual for patients who may have been suicidal. Perhaps the criteria for admission to the psych ward in Germany are different than they are in the U.S. and Canada. The still-depressed patients were in hospital an average of 4.20 days when they were tested (which was not significantly different from the recovered patients). It wasn't completely clear if any of the patients were already on antidepressants, or whether the pharmacological treatment started during hospitalization for those on meds.2 The paper did not state whether any of the depressed patients had another diagnosis, such as an anxiety disorder of any sort (co-morbidity is common).

Mean scores on the Beck Depression Inventory (BDI) were higher in the Depressed group (29.13) than in the Recovered group (16.67) or the Control participants (6.63), who also differed from each other. BDI scores of 14–19 are considered mildly depressed, 20–28 moderately depressed, and 29–63 severely depressed. So patients in the Depressed group scored at the low end of severely depressed, the Recovered participants were mildly depressed, and the Controls (n=27) were not depressed at all.

The task administered to all participants is called the "Secretary Problem":
The sequential decision-making task consisted of playing 30 games of a secretary-type problem. Each game challenged participants to find the best candidate for a job out of a sequence of 40 applicants. The 40 applicants were presented one after another, in a random sequence. After an applicant was presented, participants needed to decide whether they would accept the applicant or not. If they accepted the applicant, the game concluded and the next game started. If they rejected the applicant, the next applicant was presented. Rejected applicants could not be chosen later in that game.
Information about the current candidate included their relative ranking compared to the candidates that came before, but not their absolute ranking. Points were awarded based on the absolute ranking of the candidate chosen on each round. If a participant didn't make a choice until the end of the sequence, they were forced to accept the final candidate. So it seems that an indecisive person would be more likely to continue the search for a longer time...

Results showed there was a trend in that direction (p=.08): search length was 23.37 for Depressed, 16.87 for Recovered, and 17.96 for Controls. Performance goals for each round (how good a candidate would have to be in order to be chosen) and the relative rank of candidates did not differ between groups. However, the number of points awarded for each game did differ (p=.02): 37.67 for Depressed, 35.50 for Recovered, and 35.17 for Controls. A computational model suggested that the Depressed group had higher internal thresholds for the first and second, but not the third threshold. A caveat from the authors:
However, although we found that depressed participants had higher thresholds than did nondepressed participants, we did not find significant differences in the self-reported goals of participants. This suggests that differences in behavior may not result from participants’ conscious effort to perform well. Thus, increases in thresholds could be an artifact stemming from greater persistence and the inability to disengage from a task.
What does this mean? That severely depressed inpatients should be given the task of selecting job candidates for Fortune 500 companies, while they are so impaired otherwise that they are unable to work or function socially? Is a very modest performance benefit in a laboratory sequential decision making task worth the pain and suffering of severe depression, along with its concomitant deficits in other cognitive domains?


1 This is opposed to the Positive Psychology movement.

2 Any "recovery" from depression within six days has nothing to do with the start of antidepressants, unless it's a placebo effect. Treatment effects are generally not seen for 4-6 weeks.


Andersson S, Lövdahl H, Malt UF. (2010). Neuropsychological function in unmedicated recurrent brief depression. J Affect Disord. Jan 18. [Epub ahead of print]

Andrews PW, Thomson JA Jr. (2009). The bright side of being blue: depression as an adaptation for analyzing complex problems. Psychol Rev. 116:620-54.

Baune, B., Miller, R., McAfoose, J., Johnson, M., Quirk, F., & Mitchell, D. (2010). The role of cognitive impairment in general functioning in major depression. Psychiatry Research 176:183-9.

Hammar A, Sørensen L, Ardal G, Oedegaard KJ, Kroken R, Roness A, Lund A. (2009). Enduring cognitive dysfunction in unipolar major depression: A test-retest study using the Stroop paradigm. Scand J Psychol. 2009 Dec 23.

von Helversen, B., Wilke, A., Johnson, T., Schmid, G., & Klapp, B. (2011). Performance benefits of depression: Sequential decision making in a healthy sample and a clinically depressed sample. Journal of Abnormal Psychology DOI: 10.1037/a0023238

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Friday, May 06, 2011

Parkinson's and The Sound of Tea

In The Sound of Tea, Frank Ferraro demonstrates what happens to his manual dexterity and his gait when he goes off his regularly prescribed Parkinson's medications for an hour or two.

An entry in the Neuro Film Festival, sponsored by the American Academy of Neurology.

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