Dr Shock MD PhD

Nuanced website about the relation between serotonin transporter polymorphism and depression. The website was produced as an assignment for an undergraduate course at Davidson College. The title is: 5-HTT: The Gene for Susceptibility to Depression?

It clearly explains polymorphism and the relation with disease. Another important topic on this web page is the relation between a scientific publication and the reproduction of the results in a newspaper. The article describes the differences in interpretation between the two media.



In another article on Biology News it is explained how antidepressants block the transporter.

the drug binds to the outside of the transporter, changing its shape. This traps the brain chemical inside the tunnel like a cork in a bottle, preventing it from passing through to the inside of the neuron.

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In the 1880s, Francis Galton described a condition in which "persons...almost invariably think of numerals in visual imagery." This "peculiar habit of mind" is today called synaesthesia", and Galton's description clearly defines this condition as one in which stimuli of one sensory modality elicit sensations in another of the senses.

Read this article on Scienceblog: neurophilosophy. This article got my attention since the expressionist artist Wassily Kandinsky was also a synaesthete and Dr Shock is an admirer of Wassily Kandinski. Kandinsky in whom musical tones elicited specific colours, was a tone-colour synaesthete. Kandinsky used his synaesthesia to inform the artisitic process - he tried to capture on canvass the visual equivalent of a symphony.

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Current anti-schizophrenia drugs all work the same way, by reducing levels of the neurotransmitter dopamine in the brain. But they do not control the disease well in all patients and often have unpleasant side effects. The new drug, LY2140023, is converted in the body into a second compound, called LY404023, which acts by damping down the activity of a different neurotransmitter, glutamate.

From an article in Nature News. In a trial with 196 schizophrenic patients treatments were either LY2140023, olanzapine, or a placebo for four weeks. The drugs were roughly equally effective.

The side effects of LY2140023 are insomnia and emotional instability but the new drug did not cause weight gain.

The drug will have a long way of research to go before it possibly can be used.

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Seizure induction is the goal of Magnetic Seizure Therapy (MST) in the treatment of depression. The device for MST is borrowed from repetitive transcranial magnetic stimulation (rTMS).

The advantage of MST is the ability to produce focal stimulation. Stimulation of areas likely to be most involved in the cognitive side-effects of ECT can be more easily avoided. From studies with ECT it is hypothesized that initiation of the seizure in the prefrontal cortex explains the efficacy of bilateral electrode placement and supratreshold unilateral electrode placement. Magnetic stimulation holds the promise of more precise control over current paths and current density in neural tissue. The scalp and scull are transparent to magnetic fields. With an electric stimulus as in ECT, the current is highly variable and the distribution widespread and their is little control over the intra cerebral current density.

A drawback of MST is similar to that of ECT, patients must receive general anaesthesia with muscle paralysis during the seizure induction.

Dr Shock was reading up on his literature. While reading a review about "Targeting abnormal neural circuits in mood and anxiety disorders..." in Nature Neuroscience he read about this new technique. Searching GoPubMed he discovered 20 articles of which 6 were relevant.


Publications about Magnetic Seizure Therapy
Of these publications there were two case reports and one publication about MST in rhesus monkeys. There was one clinical trial. It is free to read, as in free beer. Ten inpatients with depression participated in a randomized, within-subject, double-blind trial. They were treated with two ECT sessions and two MST sessions, raters were unaware of the treatment schedule. MST had shorter seizure duration, lower ictal EEG amplitude and less postictal suppression. MTS sessions gave fewer subjective side-effects. MST was alos superior to ECT on measures of attention an retrograde amnesia. Efficacy was not an outcome measure.


Conclusion about Magnetic Seizure Therapy
MST is feasible in depressed patients and appears to have a superior acute side effect profile. Antidepressant efficacy needs to be esthablished.

So it will take a while before Dr Shock might have to change his name to...Dr Magnet?


Related posts:

Deep Brain Stimulation

NICE information about ECT

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Wanting to eat chocolate isn't the worse thing that can happen, but wanting and seeing chocolate is irresistible. Researchers have identified three brain regions of importance for food craving. They compared cravers to non-cravers focusing on chocolate and tested them during 5 different challenges while being brain scanned in a fMRI.


Brain centers and food craving
They used fMRI to measure the response to the flavour of chocolate,the sight of chocolate and their combination in cravers vs.non-cravers.
The cravers and non-cravers did not differ in activation of the brain regions for tasting (primary taste cortex= anterior insula).
They did differ significantly in the activation of a reward centre in the brain, the center for affective hedonic response, the orbitofrontal cortex. Not only is the affective response greater with the cravers, the combination of sight and taste of chocolate enhances the activation more than only the taste of chocolate or a picture of chocolate compared to the non-cravers.


Two other brain areas connected with the medial orbitofrontal cortex also show different responses between cravers and non cravers.
The pregenual/anterior cingulate cortex showed a greater activation in cravers to the combination of the sight and taste of chocolate. The combination produced a far greater activation than the sum of the separate conditions.
The other center the ventral striatum showed a significant greater activation to the sight of chocolate than the non-cravers. The activation on taste did not differ. The ventral striatum in cravers vs.non-cravers contributes especially to the conditioned,i.e. visual,component of chocolate craving.

The head of the nucleus caudatus also connected to the orbitofrontal cortex also showed a greater activation when the picture and the taste of chocolate were presented than the sum of the components.




Brain regions of interest for food craving:

1. the medial orbitofrontal cortex
2. ventral striatum
3. pregenual cingulate cortex



Eating in the dark when you're on a diet?
A very effective stimulus results when all of the sensory aspects of the stimuli (sight and mouth feel) are combined. This can drive behavior more in cravers than non-cravers.
Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.

Another important implication of this research as quoted from an interview with Edmund Rolls and Ciara McCabe at the University of Oxford's experimental psychology department:

This finding might offer a way of making food less pleasurable for people on a diet. "The take-home message is that if you want to limit [food] intake, you could limit the extent to which you are exposed to the combination of sight and taste. For example, you could eat in the dark", he said.

Chocoholics versus carbohydrate craving
These findings are about food craving, chocolate craving may be part of carbohydrate craving. In the publication the overlap or distinction between chocolate craving and carbohydrate craving is not made. The authors mention a questionnaire for selecting their subjects. Question 6 is "Do you crave any other food? If so, what is that food?". The answers to this question are not presented in the publication. This makes it hard to subscribe the findings of this study to chocolate alone.

And for eating in the dark, well it would hinder Dr Shock in pouring his Kopke Port 1963 which goes perfectly well with his dark chocolate.


Other articles about chocolate on this blog:

Is Chocolate an Antidepressant?

Side effects from Chocolate


Article discussed:
Edmund T. Rolls, Ciara McCabe (2007)
Enhanced affective brain representations of chocolate in cravers vs. non-cravers
European Journal of Neuroscience 26 (4), 1067–1076.
Abstract

Related post on Finding Optimism written by Leo Babauta from zen habits: 5 Powerful Reasons to Eat Slower

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In this last week 2 additional sites with trustworthy information about ECT were discovered.

Electroconvulsive Therapy Consensus Development Conference Statement. This information is presented by National Institutes of Health in conjunction with the National Institute of Mental Health on a Consensus Development Conference on Electroconvulsive Therapy on June 10-12, 1985.
A consensus panel representing psychiatry, psychology, neurology, psychopharmacology, epidemiology, law, and the general public considered the scientific evidence and agreed on answers to the important questions about this treatment.

More recent and up to date is information about Electroconvulsive Therapy (ECT) by Dr. Raymond Crowe, MD Professor of Psychiatry University of Iowa Department of Psychiatry Peer Review Status: Internally Peer Reviewed
First Published: March 2000
Last Revised: December 2004


Previous articles about Electroconvulsive therapy (ECT) on this blog:

Predict Treatment Response with ECT

Patient sharing his experiences with ECT on YouTube

Cognitive side-effects of ECT in Adolescents

Myths and stigma's about ECT

Boook chapter about ECT in Neuropsychopharmacology

Brain perfusion and electroconvulsive therapy

Electroconvulsive therapy and pregnancy

NICE guidelines for ECT

Dutch Elderly afraid of ECT

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Abott Lab removed the sentence "increased risk of cancer" as mentioned for their arthritis drug Adalimumab (brand name Humira) on Wikipedia.

Two minutes later, someone with the username Gscshoyru, whose Wikipedia profile describes him as a “recent changes patroller,” added the information back to the entry.

Jeffrey Light, who runs the one-man nonprofit Patients not Patents used Wikipedia Scanner to see what the drug industry had been up to on Wikipedia. He made a press release on this subject, you can download this press release from the article on HealthBlog from the Wall Street Journal.

Wikipedia Scanner -- the brainchild of Cal Tech computation and neural-systems graduate student Virgil Griffith.
This software offers users a searchable database that ties millions of anonymous Wikipedia edits to organizations where those edits apparently originated, by cross-referencing the edits with data on who owns the associated block of internet IP addresses.

This is the second drug company that was discovered doing this. The other company was AstraZeneca for their drug seroquel. Would like to use WikiScanner on some other drug companies as well, but it takes a lot of time.

Other post on this subject on this blog:
Drug company rewrites entry on Wikipedia

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50 to 60 % of patients with a depressive disorder fail to respond to their first antidepressant. These rates increase in clinical practice setting to 65 to 85%. Estimates of TRD prevalence varies greatly depending on treatment setting. The lowest TRD prevalence is in primary care and progressevily higher rates occur in outpatient psychiatric settings, inpatients settings and academic tertiairy setting.

Compared to non-TRD, TRD patients have been reported to have significantly higher outpatient medical costs, and to be approximately twice as likely to be hospitalized, either medically or psychiatrically

From: Nemeroff CB. J Clin Psychiatry. 2007;68 Suppl 8:17-25.
Prevalence and management of treatment-resistant depression. Abstract


What is Treatment-Resistant Depression?
An inadequate response to an adequate course of treatment in a patient meeting criteria for major depressive disorder. Treatment is usually antidepresssants. Depression is not bipolar depression. This diagnoses needs a different approach. An adequate course is a course of an adequate dosage of the antidepressant for at least 6 weeks. This has been operationalized in criteria for different stages of TRD:

Stage 1. Failure of an adequate trial of 1 class of antidepressant

Stage 2. Failure of adequate trials of 2 distinctly different classes of antidepressants

Stage 3. Stage 2 plus failure of a third class of antidepressant, including a tricyclic antidepressant

Stage 4. Stage 3 plus failure of an adequate trial of a monoamine oxidase inhibitor

Stage 5. Stage 4 plus failure of an adequate course of electroconvulsive therapy

From: Thase ME, Rush AJ. J Clin Psychiatry. 1997;58 Suppl 13:23-9.When at first you don't succeed: sequential strategies for antidepressant
nonresponders. Abstract

What can they do about Treatment-Resistant Depression?

1. Be sure they diagnosed the depression properly, subtype of depression

2. Exclude somatic illness

3. Exclude comorbid psychiatric illness

4. Evaluate antidepressant treatment for compliance, tolerabillity, duration, and dosage. If necessary optimize by increasing dosage or extending the duration.

5. Switch to an other antidepressant if previous measures failed

6. Augment the antidepressant

7. After cessation of all antidepressants start a monoamine oxidase inhibitor

8. Reconsider diagnoses and use Electroconvuslive therapy

9. Don't forget cognitive therapy, Interpersonal psychotherapy, running therapy, family therapy.

Treatment algorithm for Treatment-Resistant Depressed Inpatients

In a recent study some of these steps were studied in a treatment algorithm with depressed patients admitted to a depression unit.

Step 0: Washout, Diagnostic phase, and placebo run-in (1 week)

Step 1: Antidepressant monotherapy (imipramine or fluvoxamine; 6 weeks)

Step 2: Lithium addition (5 weeks)

Step 3: Nonselective monoamine oxidase inhibitor (MAOI; phenelzine or tranylcypromine; 5 weeks)

Step 4: Electroconvulsive therapy (flexible number of weeks)

Results of a treatment algorithm for treatment-resistant depression

149 patients (50%) were included in the 4-step algorithm. Of the 56 patients who were excluded from
step 1 because of proven refractoriness to antidepressants during the index episode, 54 were enrolled directly into step 3 of the algorithm. Only 4 (7%) of these 54 patients had received lithium addition. Ten patients needed immediate ECT.

At the end of the algorithm, 129 (87%) of 149 patients achieved response. Complete remission was achieved by 89 of 149 (60%) patients. Three patients switched into
hypomania during the algorithm: 2 receiving a combination of imipramine and lithium and 1 patient receiving phenelzine. These patients were considered both as responders and remitters. Overall dropout of the algorithm amounted to 24 (16%) of 149 patients. When including patients who entered the algorithm at step 3 (treatment with a nonselective MAOI) the figures are as follows: 165 (81%) of 203 responded during the algorithm and 101 (50%) achieved remission. Overall dropout, including the 54 additional patients, was 30 of 203, i.e., 15%.

These results emphasizes the importance of persisting with stepwise antidepressant treatment in non-responders to the first antidepressant. Important is to note that this trial was done on a depression unit in a academic/tertiary centre.

From: Birkenhäger TK, van den Broek WW, Moleman P, Bruijn JA. J Clin Psychiatry. 2006 Aug;67(8):266-71. Outcome of a 4-step treatment algorithm for depressed inpatients. Abstract


I was inspired by an article from the MayoClinic.com about Treatment-resistant depression

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Your genes probably predict response to ECT more accurate then any clinical variable.

Genes, enzymes and neurotransmitters
Genes are located on DNA in the nucleus of the cells in your body. You usually have two genes on each arm of a chromosome ( one from dad and one from mum). If the two genes are identical it's called that they are homozygote, if they are different it is heterozygote. Genes are read by other cell nucleus material (RNA) which starts a sequence to produce proteins. The most important proteins being enzymes. Enzymes are needed for the metabolism of neurotransmitters among others. Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a neuron and another cell in the brain.
Catechol-O-MethylTransferase (COMT) is a major enzyme in the brain for the metabolism of dopamine, a neurotransmitter. A polymorphism in the gene coding for COMT results in substantial effects, with a homozygote allele variant leading to a three to fourfold reduction in enzymatic activity compared to the other homozygote variant.
In general, polymorphism describes multiple possible states for a single property. This single property being a single amino-acid sequence in the allele for COMT. The presence of Met/Met and Met/Val or Val/Met results in a much lower activity of COMT than Val/Val (high activity).



Low Dopamine concentration in Prefrontal Cortex
The high genotype of COMT was associated with better treatment response to ECT than low allele containing genotypes. Since high genotype results in a high activity of COMT and a low dopamine concentration in the prefrontal cortex we can assume that low dopaminergic activity in the prefrontal cortex is associated with a better response to ECT.


This was shown in 119 treatment-refractory depressed patients admitted consecutively for electroconvulsive therapy (ECT). The effect of clinical variables also related to a better response to ECT were studied using univariate analysis of variance. These covariates: higher illness severity, age, age at onset, sex and the number of ECT treatment did not affect the treatment response.


Not all studies with COMT polymorphism and response to antidepressants found an association between this polymorphism and response. COMT also plays a role in the metabolism of norepinephrine, another important neurotransmitter in the brain. Other limitations of this study are a small patient sample and the concomitant use of psychotropic drugs during ECT. ECT itself was properly performed.



Biological variables predicting response
A very nice publication in a new field of research. Important topic predicting response in a patient with biological variables.



Publication:
Catechol-O-methyltransferase(COMT) polymorphisms predict treatment response in electroconvulsivetherapy

The Pharmacogenomics Journal (2007),1–4.

Sami Anttila et al.



Correspondence:

Dr S Anttila,Department of Psychiatry,

Tampere University Hospital,Pitkaniemi

33380,Finland.

Abstract

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Most scientist know PubMed. It is a powerfull search engine for scientific literature. It is a bit dull, not so very geeky. In comes Gopubmed. It has the power of PubMed and then some more. It has some nice graphic as well as usability improvements compared to the original PubMed. The results page is divided into two sections. On the right hand side the latest 1000 PubMed citations that match your search term. But the fun is on the top of the right side:

If you click the “show statistics for these 1000 articles” you get the citations summarized on the basis of a number of variables such as top authors, journals, cities, countries and years. This is pretty nifty if you want to get an idea of who is publishing most in the area, where the publications are coming from and what journals are publishing that kind of content. Some examples of the statistical analyses are shown below. Another cool thing is you can click on names, journal and locations to get those specific citations.

On PsychPlash these add ons are illustrated with graphics from gopubmed.



On the left-hand side :
1. Gopubmed annotates the resulting citations with GO and MeSH terms
2. Content Filters are extremely useful in helping you answer specific questions relating to your initial search query
3. The Document Filters are the same as the citation statistics mentioned in the blockquote above
4. The site has an extensive help function.


Try electroconvulsive therapy. The next picture is the top 20 cities and countries with this search term. Is that The Netherlands on place 6?

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Trusted.MD is conducting a new survey about medblogs. If you're a health care blogger do the survey

WHY WE NEED YOUR HELP

We can't continue to get a better understanding of the healthcare blogosphere without your help. We need as many healthcare bloggers (those devoting at least 30% of their blogging time to healthcare) to take the survey so that we can make valid conclusions about the size and shape of this growing part of the global blogging community.

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In the recent past I was interested in search engines. You have different kind of search engines, the most famous being Google. Google is a traditional search engine.

A meta-search engine is a search engine that sends user requests to several other search engines and/or databases and returns the results from each one. Meta search enables users to enter search criteria once and access several search engines simultaneously. Since it is hard to catalogue the entire web, the idea is that by searching multiple search engines you are able to search more of the web in less time and do it with only one click. The ease of use and high probability of finding the desired page(s) make metasearch engines popular with those who are willing to weed through the lists of irrelevant 'matches'. Another use is to get at least some results when no result had been obtained with traditional search engines.

Science Roll , A medical student's journey inside genetics and medicine through web 2.0, had an article about a new meta search engine: AllPlus
It delivers results from:

• relevant sites/articles
• blogs
• news
• relevant images and videos
• cluster tree and graph

Try electroconvulsive therapy

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Only 1 in 10 medical clinical professors are women in the United Kingdom (UK). No female professor was employed in 6 medical schools. The newer medical schools had a better gender balance than some of the more established schools.
For the lower ranks in medical academia these numbers are somewhat higher but still much lower than for men.
In FTEs lecturers in 2005: 36% were women, senior lecturers and readers: 25% were women. In 2005 there were a total of 3365 clinical academics, of whom 21% were women. There was a wide range in the number of professors per speciality; the majority were physicians. The percentage of women professors ranged from 0% (in occupational medicine) to 20% and over (e.g. in radiology, general practice). This gender difference remained relatively constant between 2004 and 2005.

These results were published in Medical Education. This study was needed since data available about gender-specific workforce in clinical academics were limited. These data are reported in order to allow comparison over time.

These data are also supported by a publication in the NEJM in July 2006 about The Gender Gap in Autorship of Academic Medical Literature.

Conclusions Over the past four decades, the proportion of women among both first and senior physician-authors of original research in the United States has significantly increased. Nevertheless, women still compose a minority of the authors of original research and guest editorials in the journals studied.

The United States of America is a favourable exception when it comes to enhancing the careers of women in clinical academics. In Europe conditions are far worse on academic careers for women.

Women and Science in Europe

Source: Women and Science Statistics and Indicators

Women and Science in The Netherlands
In The Netherlands 400 female professors are needed in the coming years in order to answer the European agreements in 2010.

What hinders academic careers for women?
1. Lack of role models and support for female staff
2. Family/carer commitments
3. Lack of network because there aren't many females. Men seem to help each other more to get in key positions
4. High levels of teaching, administrative and pastoral care loads for women. These tasks are not recognised as much as research output
5. Discrimination. Part time work in women is seen as lack of commitment
6. Generational and other issues. A large number of baby boomers in senior positions are not moving on.

For more information and staying up to date see the blog Women in Science.

Women and Science is dedicated to the women in science and engineering, past and present.

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" If you can't take good care of yourself, how can you take care off your patients?", this is what I tell my residents at least once during their training. 60 to 80 working hours a week is not taking good care of yourself nor your patients.

You can't perform well with this schedule, you can't be patient, you will make mistakes, especially when working long hours at a stretch. Pilots know that and doctors should as well. Tutors should be role models for residents and teach them that they are responsible for their own performance. They should discourage the macho attitude of doctors being able to work long hours, it being part of their job. It is in contempt of their responsibilities and patients entrusted in their care.

Patient-doctor interaction
Another important topic is how a doctor can remain sensitive to the demands of his or her patients. In other words how can a doctor be empathic without loosing his professional distance necessary for good judgment and decision making. Avoiding excessive emotional involvement which can harm his care for the patient, obscure his clinical judgment.


In order to introduce medical students to this responsibility the book: The case of Dr Sachs and the film La maladie de Sachs is recommended by Josep-Eladi Baños from Barcelona, Spain. He wrote a letter to the editor of one of my favorite journals: Medical Education.
In this book and film a French doctor practising in a rural area has a "disease".

The symptoms of his disease involve excessive worry about his work of caring for other people, to a point where he neglects to care for himself and devotes most of his time to doctoring.

Another suggestion for introducing medical students to their future activities he recommends: A Taste of My Own Medicine: When the Doctor Is the Patient
In this book and the film "The Doctor" based on this book the author describes how it feels to be diagnosed with a severe illness, along with all the feelings of uncertainty and fear.

The book is especially revealing about how a doctor might feel when he is treated as a patient and how he considers the disease from the perspective of a patient

The author of the letter to the editor recommends that it is easier to discuss the films than the literary works, the focus being the doctor-patient relationship.
The two suggested books and films are excellent teaching material for medical students on the topic off patient-doctor relationship.

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As a clinician I always wondered why some abused patients had more trouble recovering from their psychiatric illness than others. This article about the gene environment interaction in Psychiatry clarifies some of the variations in outcome. This article explains in relatively accessible written prose some of the experiments that have influenced our thinking about gene and environment interactions in relation to psychiatry. It is written by David D. Olds, M.D. Columbia College of Physicians and Surgeons New York.
He teaches clinical psychiatry and psychoanalysis at Columbia University and is an editor of the journal Neuro-Psychoanalysis. He has written often on the relationship between neuroscience and psychotherapy. Wanted to comment on his article. Curious how psychotherapy with sexually and or physically abused patients influences our brains or perhaps even genes. Maybe a topic for a future article on this blog.

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No severe cognitive side effects of ECT used on adolescents could be demonstrated. ECT in adults causes memory complaints, retrograde and anterograde amnesia. The tests used in trials with adolescents are limited in measuring these side effects. Moreover there are no prospective studies on this subject with adolescents and the studies discussed have a small number of subjects with possible lack of statistical power.

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Dr Shock usually "hangs" in his chair. It feels comfortable. Read in this article in LifeScience why sitting up straight might be a bad advice. Scientifically tested with magnetic resonance imaging (MRI).

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I read the first edition of this book while on holiday in France. We were cross-country skiing. Not that the weather was bad or the company boring but this book is very informative and easy to read. Read all the other editions as well. For me it is the most narrative book about ECT with a critical appraisal of all the scientific literature. Obviously written by an experienced and good clinician.
This book is reviewed on Medical Heaven, I couldn't have done a better job.

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A list of medical blogs based on a algorithm with the number of comments, posts, feed readers, incoming links. You can see the widget about it in my sidebar.
Here is a discussion about rating medical blogs.

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