Friday, September 5, 2008

All I Really Need to Know About Serotonin I Learned in Kindergarten

This article (A), which quotes the findings of this study (B) is another example of the misrepresentation of research. The actual study makes claims not supported by its findings and misrepresents the researched cited within the text.

First, the article title at ScienceDaily (SD) is "PET Scans Help Identify Mechanism Underlying Seasonal Mood Changes." No. They should have used the actual study title "Seasonal Variation in Human Brain Serotonin Transporter Binding." That's strange, I don't see the word "mood" anywhere. Hold on, let me get my glasses. Wait a minute, I don't wear glasses. I can see after all.

Since the rest of the SD article is just quotes lifted from the study, I'll just focus on the study itself. "Indolamines (tryptophan, serotonin, melatonin, and related compounds) have transduced light signals and information on photoperiod into organisms and cells since early in evolution, and their role in signaling change of seasons is preserved in humans. " The study cited for this statement (3) is for melatonin only, an indolamine, not indolamines. Secondly, tryptophan is the precursor amino acid that is converted into serotonin and melatonin (i.e., indolamines are neurotransmitters that are synthesized from tryptophan, a standard amino acid).

"Serotonin is involved in the regulation of many physiologic and pathologic behaviors that vary with season in clinical and nonclinical populations.3-12" Maybe it's just me, but when I read this sentence, I assumed that the 9 studies referenced would support the role of serotonin "in the regulation of many physiologic and pathologic behaviors that vary with season." No. Studies 3-11 establish that seasonal mood changes occur in healthy people and in some clinical populations. Only study 12 has anything to do with the serotonin. The serotonin transporter (SERT) specifically. The words "mood" or "depression" are nowhere to be found in that article. The researchers should have said "there is substantial evidence indicating that moods vary by season in both healthy and clinical populations. The role of serotonin is currently unknown."

"Seasonal variations in peripheral serotonergic markers have been demonstrated in several studies." 3 studies are cited and the studies do support this statement. I don't know if 3 constitutes "several," but at least the above statement is accurate. See, that's what happens when you actually read the work you cite.

"...the seasonal variation in serotonin-related behaviors,3-12" Nope. They cite the same studies where only one is about SERT. I want evidence that seasonal mood variations are "serotonin-related behaviors."

"Previous investigations19-20 of regional serotonin transporter binding and season in humans have not led to a clear understanding of the relationship between these 2 measures." That's probably due to the fact that those two studies cited have nothing to with serotonin binding and the seasons. The first study (19) investigated the effects of MDMA and reduction of SERT. The word "season" doesn't appear in the article. The second study (20) is a review of MDD and AD imaging studies. Again, the word "season" is not in the article. Later, they cite two other studies (21, 22). The first study actually is about seasonal SERT changes while the second article focused on that topic secondarily. Maybe the researchers intended to cite references 21 and 22, instead of 19 and 20.

The researchers reach this conclusions about their study, "Serotonin transporter binding potential values vary throughout the year with the seasons." Yes, I'm with you so far, "Since higher serotonin transporter density is associated with lower synaptic serotonin levels, regulation of serotonin transporter density by season...has the potential to explain seasonal changes in normal and pathologic behaviors." Do you have any leftover "No's" from this post (C)? I suggest that you use them now.

Synaptic serotonin levels cannot be directly measured in vivo. So how is it measured? They measure the presence of its metabolite, 5HIAA. Next fact, 95% of all serotonin is in the stomach (D). So, how is low serum 5HIAA a measurement of brain serotonin? It's not. Make sense now? No? Good, let's move on.

"Higher regional serotonin transporter binding potential values in fall and winter may explain hyposerotonergic [related to low serotonin levels] symptoms, such as lack of energy, fatigue, overeating and increased duration of sleep during the dark season."Actually those behaviors are better explained by low cortisol (E). If cortisol is low, the liver cannot synthesize glucose, which leads to lack of energy, fatigue, and increased sleep. People eat more food (especially those high in carbs) in order to increase glucose, which will give them energy.

Still confused? Read this to learn more about serotonin and mood (F).


Mark p.s. said...

I love the title."All I Really Need to Know About Serotonin I Learned in Kindergarten".

Anonymous said...

Serotonin Medications: Do the Risks Outweigh Any Benefits?

Presently, for the treatment of depression and other mental disorders, some of these disorders are questionable regarding thier existence, the preferred choice of medicinal treatment are a class of medications called selective serotonin reuptake inhibitors, referred to as SSRIs, as they are the drugs of choice by most prescribers. Such meds, meds that affect the mind, are called psychotropic medications. SSRIs also include a few meds in this class with the addition of a norepinephrine uptake inhibitor added to the SSRI, and these are referred to SNRI medications. Examples of SNRIs are Effexor and Cymbalta. Presently, some compare the usage and popularity of these classes of meds as that of the usage of tranquilizers decades ago.
Some Definitions:
Serotonin is a neurotransmitter thought to be associated with mood. The hypothesis was first suggested in the mid 1960s that this neurotransmitter may play a role in moods and emotions in humans. Yet to this day, the serotonin correlation with such behavioral and mental conditions and diseases is only theoretical. In fact, the psychiatrist’s bible, which is called the DSM, states that the definite etiology of depression remains a mystery and is unknown. So a claim of a chemical imbalance in the brain as a reason for depression is not proven to be the cause of this and other mood disorders, it is only suspected based on limited science, which may or may not be valid. Observation by one's doctor is usually the determining factor for such a diagnosis.
Norepinephrine is a stress hormone, which many believe help those who have such mood disorders as depression. Perhaps this is now added to SSRIs for additional efficacy for those treated with these medications.
And depression is only one of those mood disorders, yet possibly the most devastating one. Once again, an accurate diagnosis of these mood conditions lack complete accuracy as they can only be defined conceptually, so the diagnosis is dependent on subjective criteria, such as questionnaires, as there is no diagnostic testing available to conclude objective diagnosis of such disorders. However, the diagnosis of depression in patients has increased quite a bit over the decades. While most likely a real disease, most will agree, misdiagnosis does occur due to the subjective assessment that determines the disease, as perhaps one out of every four people diagnosed with depression is inaccurate.
Several decades ago, less than 1 percent of the U.S. population were thought to have depression. Today, it is believed that about 10 percent of the population have depression at some time in their lives. Why this great increase in the growth in the assessment of this condition remains unknown and is subject to speculation. What is known is that the psychiatry specialty is the one specialty most paid to by certain pharmaceutical companies for various forms of support, as this industry clearly desires market growth of their psychotropic products, such as SSRIs, since clearly this is part of their nature and objective as a pharmaceutical company. Regardless, SSRIs and SRNIs are the preferred treatment methods if depression or other certain mood disorders that may be suspected by a doctor.
Over 30 million scripts of these types of meds are written annually, and the franchise is around 20 billion dollars a year, with some of the meds costing over 3 dollars per tablet. There are about ten different SSRI/SRNI meds available, many of which are now generic, yet essentially, they appear to be similar in regards to their efficacy and adverse events. The newest one, a SNRI called Pristiq, was approved this month and is expected to be promoted primarily for the treatment for menopause. Conversely, the first one of these SSRI meds was Prozac, which was available in 1988, and the drug was greatly praised for its ability to transform the lives of those who consumed this medication in the years that followed. Some termed Prozac, ‘the happy pill’. As years passed, this drug was preferred for children with depression. Also, a book was written praising Prozac as a euphoric entity for all to experience.
Furthermore, these meds have received additional indications for really questionable conditions, such as social phobia and premenstrual syndrome. With the latter, I find it hard to believe that a natural female experience can be considered a treatable disease. With social phobia, many would say that is a personality trait and, in my opinion, is synonomous with shyness, which probably should not be labeled a treatable disease as well. There are other indications for certain behavioral manifestations with the different SSRIs or SRNIs. So the market continues to grow with these meds- assisted by thier manufacturers. Yet, it is believed that these meds are effective in only about half of those who take them. Also, the makers of such meds create such conditions for utilization of these types of medications, in my opinion, and are active with related support groups who are funded by the makers of such drugs, such as sponsoring screenings for the indicated and not indicated conditions of their meds, including children and adolescents in particular, it is believed. Yet depression, which has clearly has been proven to be devastating to the victim, such screenings are controversial due to possible bias involved in seeking those with mental illness in this manner.
More concerning, however, is the adverse effects associated with SSRIs and SRNIs, which include suicidal thoughts and actions, as well as violence, including acts of homicide and aggression. The associations with these actions have been established with these types of meds. While most are approved for use in adults only, prescribing these meds to children and adolescents has drawn the most attention to others through the media. The reasons for this attention are the off-label use of these meds in this population, and the association with suicide. What may be most shocking is the fact that some of the makers of these meds did not release clinical study information about the risks of suicide as well as the other adverse events and true efficacy of certain types of SSRI meds, including the decreased efficacy of SSRIs, which is believed to be only less than 10 percent more effective than a placebo, until ultimately the makers of such drugs were forced to do so. Paxil, for example, caught the attention of the government regarding these issues some time ago for hiding and not presenting such important information to others, for example.
And there are very serious questions about the use of SSRIs in children and adolescents regarding the effects of these meds on them. For example, do the SSRIs correct or create brain states considered not within normal limits, which in effect may worsen thier mental state? Are adolescents depressed, or just experiencing what was once considered normal teenage angst? Do SSRIs have an effect on the brain development and their identity? Do adolescents in particular become dangerous or bizarre due to SSRIs interfering with the myelination occurring in their still developing brains? No one seems to know the correct answer to such questions, yet the danger associated with the use of SSRIs does in fact exist. It exists in some who take such meds, but not all who take these meds. Yet more need to be aware of such possibilities, some say.
Finally, if SSRIs are discontinued by those who have taken them for certain periods of time, withdrawals have been reported to be quite brutal, and may be a catalyst for suicide in itself, as not only are these meds habit- forming, but discontinuing these meds leaves the brain in a state of neurochemical instability, as the neurons are recalibrating upon discontinuation of the SSRI after being altered by the med to some degree. This occurs to some level with any psychotropic med, yet the withdrawals can reach a state of danger for the victim in some classes of meds such as the case with SSRIs.
SSRIs and SRNIs have been claimed by doctors and patients to be extremely beneficial for the patient’s well -being regarding the patient’s issues involved with thier mental illness suspected, such as depression, yet the risk factors associated with this class of medications may outweigh any perceived benefit for the patient taking such a drug, and this may want to be explored more by others. Considering the lack of efficacy that has been demonstrated objectively, along with the deadly adverse events with these meds only recently brought to the attention of others, other treatment options should probably be considered at the discretion of your prescriber.

“I use to care, but now I take a pill for that.” --- Author unknown

Dan Abshear