The Google of Negative Results

A new online resource has been launched which offers us the chance to find out what isn't happening in science.

BioNOT is a free searchable database of negative findings in biology and medicine.

Text mining approaches to the scientific literature have become increasingly popular as a way of helping researchers to make sense of a growing number of papers. But they've tended to focus on positive findings and skim over negative ones. In this sense they're following in the tradition of scientists themselves, unfortunately.

It's also hard to search for negative findings on PubMed, because if you type in, say, vaccines NOT associated with autism in the hopes of finding papers showing that vaccines don't cause autism, it will think you are trying to search for "vaccines" and don't want to see any papers mentioning the words "associated with autism". So you end up with 160,000 hits about vaccines with no reference to autism at all. There are ways around this but it's surprisingly tricky.

BioNOT uses text mining to mine null findings from a large database which includes everything you can find on PubMed and also a large number of full text articles (some behind paywalls).

Authors Agarwal et al of Wisconsin say that this will help to map out the "incidentalome" (a brilliant word I'd never heard before) for a given disease or trait i.e. the regions of the genome that turned out not to be associated with it. It should work for anything, though, not just genes.

However the BioNOT system isn't perfect. The authors note that it is rather over-enthusiastic in finding negative sentences.

A quick try on the system bears this out. I searched for 5 HTTLPR, the claimed "happiness gene". This revealed many papers finding no link between the gene and various things. But it also threw up false positives (how ironic), such as:

young rhesus monkeys were split into two groups... those having, or not, the short variant of the 5 -HTTLPR polymorphism

This is just telling us about the methods of a study. It's not a null finding, but it set the BioNOT alarm bells ringing, presumably because it contained the word "not".

So BioNOT is only a first step, but it's an important one.


Agarwal S, Yu H, & Kohane I (2011). BioNOT: A searchable database of biomedical negated sentences. BMC bioinformatics, 12 (1) PMID: 22032181

Today's LGBT History Month Icon: Pedro Zamora

New Santorum Campaign Ad

Lagging behind in the polls, it looks like Santorum is trying to appeal to the religious extremists by telling them that God told him to run for President. The ad, by the way, says nothing about why he'd make a good president. 

New Marriage Equality Ads in Maine

New marriage equality ads are hitting TVs in Maine. Here's one featuring Paul and Jeanette Rediker, a straight Maine couple with a gay daughter:

In 2009, a "people's veto" reversed legislation that would have legalized marriage equality in Maine. Supporters of marriage equality are now trying to reverse that action through the very same process. 

Ad Spotlight: Absolut Vodka

Absolut is celebrating 20 years of LGBT advertising. In 1981 it ran its first gay-targeted ads in The Advocate and After Dark. To celebrate, Absolut is launching a national $4 million outdoor, digital, and print campaign. Click here to read the full New York Times article.

Earthquake

It has been a while since I've felt an earthquake. But last night changed all that. We stayed here, at Lake Tahoe, in order to do so some winterizing, cover the patio furniture, meet with the furnace man to have the furnace serviced, etc.

Sometime after going to bed I felt the bed shaking - I grabbed my husband, thinking he was having some kind of seizure, (although he has never had one), or thought maybe the dog was doing it somehow. It was a pretty good shake. My husband appeared to be fine so I didn't think anything more of it when this morning he mentioned not seeing anything in the news about the earthquake last night. Earthquake? Is that what all the shaking was about?

Living in Reno, we're used to tremblers. I've felt quakes that literally rocked the furniture, but it hasn't happened in many years. We know that earthquakes have been swarming in recent months. I read that there were over 150 small ones right under our house. But we've never felt one at Lake Tahoe. It reminds me of this post on Mountain Tsunamis. They are possible here in the mountains, reminding me to make sure that our emergency plan takes into account that we spend a great deal of time here.

Most of us live in areas that have some kind of danger, lets face it. If Washington DC, and New York City can have an earthquake, despite being in an area of low seismic activity, then they can happen anywhere. Even if you're not sitting on a fault line, you are still residing on the earth's crust, and there is movement going on right underneath.

It reminds me to be thankful, once again, for each day, each minute, each blessing. This warm little house is a gift, and so many are without such luxury. My thoughts are with those in Turkey right now, those who were not so lucky as to just have had their bed shake.

Update: It was a 4.7 located 35 miles west of Reno.

The Teen Happiness Gene?

Whether you were happy with life as a teenager could be down to a certain gene, says a new study.

In a large study of American adolescents, the AddHealth project, teens who carried the long form of the 5HTTLPR locus were more likely to say they were satisfied or very satisified with their lives (at age 18 to 26). People with two long variants were the most cheerful, with short/long carriers in the middle and short/short being the least so.

The effect was significant controlling for ethnicity (p=0.013), however looking at the data shows that this effect was largely driven by the unhappy teens who reported being "Dissatisfied" or "Neither" on the 5 point scale of life satisfaction - but there were only a small number of these, because the great majority said they were "Satisfied" or "Very Satisfied". Still, there you go.

Incidentally, Neuroskeptic readers may remember AddHealth because of its role in the "black women are ugly" race row from earlier this year.

This study is the latest in a long, long line of attempts to correlate 5HTTLPR with happiness, depression, stress and so on. A few months ago I discussed the history of this busy little gene and covered a meta-analysis of no fewer than 54 papers which claimed that there was indeed a link, with the short allele increasing the risk of depression in response to stressful events.

However many studies failed to find one, and worryingly the three largest studies were all negative which is a classic tell-tale sign of publication bias - maybe people were only bothering to publish smaller studies if they did find a link and hence were "exciting findings". This is quite possible because so many researchers collect DNA as part of psychology studies these days. When the 5HTTLPR story got big (about 5 years ago) I know a lot of people decided to jump on the bandwagon by looking at it in the context of their old data.

Personally I have no idea whether 5HTTLPR is associated with anything. I used to think it probably did, but now I'm just confusion. There have been so many studies and so much inconsistency that it's very hard to know. What worries me is that I'm not sure whether we'll ever get a consensus. We've already had a gigantic study (over 80,000 people) showing no link and many meta-analyses coming to different conclusions.

What will it take to settle the issue? An even bigger study? Would 200,000 people do it? A million? I don't know.

De Neve JE (2011). Functional polymorphism (5-HTTLPR) in the serotonin transporter gene is associated with subjective well-being: evidence from a US nationally representative sample. Journal of human genetics, 56 (6), 456-9 PMID: 21562513

New Stat on Support for Marriage Equality by Age

No surprises in the pattern here. Again, I'd be curious to see how the question was phrased. As I always caveat when sharing marriage equality data, in my opinion the question should be phrased as, "Do you believe same-sex couples should have the right to access civil marriage licenses?" This is because there is a difference between "favoring something" and believing people should have the right to it. As an example, some redneck American out there might not personally "favor" interracial marriage, but that doesn't necessarily mean he believes interracial couples out there shouldn't have the right to marry. Furthermore, the distinction between the two types of marriage - civil and religious - must always be made clear when it comes to polling on this issue. Language matters. 

Study Paints a Better Picture of Today's Real Modern Family

Edelman has just wrapped up an interesting study on changing US family dynamic and demographics. Among the most interesting findings include that just 4% of US families have stay-at-home moms and working dads with children under 18 years old. That's right, just 4%. Furthermore, the study points out how economic pressures and blended family models have redefined individual roles within the family: skill sets have replaced gender, and 62 percent of moms and 54 percent of dads feel that parenting roles will be redefined away from the traditional “mom and dad” roles of the past. This creates a new opportunity for marketers to think in terms of skill set versus gender, opening up the entire family as a target. The study, which was commissioned in August 2011, included in-depth interviews with 2,482 consumers among a cross-section of today’s modern family: single parents, working moms, gay partners, multicultural heads of households and grandparents.

Today's LGBT History Month Icon: Dan Savage

Events

Whether you are a believer or not, it's obvious the world is amassing some major events. It has been a wild week - especially for Libya, Turkey (earthquake), Thailand (flooding), and of course, here in America with the GOP debates. (Always entertaining in a sad sort of way.) Not to mention Occupy "Everywhere." (I think the sleeping masses are beginning to stir.) We also have a hurricane building as we speak.

So here are a few things I have my eye on:

We have a new moon in Scorpio on the 26th - which is supposed to be great for new beginnings. Or in my case new partnerships. You can read all about that here, and find out what that might mean for you.

The end of the Mayan calendar ends on Friday, if Dr. Calleman is correct, as his date is different from December 21, 2012. You can read about that here.

We have 11-11-11 coming up just around the corner and the Mayan elders have revealed some new information. They have always kept their traditions within their inner circles, but have now been instructed to perform all of their ceremonies in public. The Ceremony of The Thirteen Skulls was last performed 26,000 years ago. They will be traveling with the thirteen Crystal Skulls from New York to Los Angeles for the end ceremony on 11-11-11, with several stops along the way. You can read all about that here, just in case you are like me and had no idea what the Crystal Skulls are all about. Now I wish I was available to watch a ceremony - maybe in Sedona.

Dr. Kashonia has done an in-depth analysis on geomagnetic and total pole reversals, and how they may tie in with 2012 prophecy. You can read about that here, just in case that has been a concern of yours. As you can see - she has been busy. I always like her research because she uses a variety of sources and utilizes critical thinking in her analyses.

We had a major solar flare yesterday, compressing Earth's magnetic field, you can read about that here.

With all that's going on in the world right now, I guess it's time to relax, think good thoughts, make sure you are prepared in case of an emergency, and then hang on, because this roller coaster seems to be picking up speed.

The Limits of (Neuro)science

Will science ever understand the brain?

To start off with, it must be admitted that science has done a pretty good job of explaining pretty much everything else in the universe, so just going on past experience, it probably will.

But some say that, sure, the scientific method is fine for things like chemistry, but not for others. The human brain (or some aspect of it: consciousness, the mind, love, belief, or whatever) is the most popular exception. Science just won't work on it, we're told. It's too complex.

Maybe, but I find this view rather blinkered. It relies on taking our current state of knowledge as an eternal truth.

To see humanity as a mystery surrounded by a world of unmysterious things is a very new idea. It would have seemed bizarre just 300 years ago. Back then, nature was pretty much inscrutable. At best human life was no more mysterious. In many ways, less so. There were no end of philosophical, psychological and religious theories, many of them so plausible that they're still around today.

The notion that humans are complex and hard, while nature is easy, is an illusion created (ironically) by the successes of reductionist science. Some of the biggest questions facing mankind for eons have answered so well, that we don't even see them as questions. Why do people get sick? Bacteria and viruses. Why does the sun shine? Nuclear fusion. Easy.

But only easy now. Think of the billions of people who lived and died before say 1800 - they saw the sun every day and they had no idea why it shone, and they knew no-one else did. You may not understand nuclear fusion, but you know that physicists do, you know it's no mystery. 300 years ago, it would have been very tempting to think that no-one would ever know, that the answers were known only by God.

So, to confidently claim that explaining the human mind will just be too hard is presumptuous. It may or may not be, I don't know. Historically, though, the theory that things are inexplicable has a bad track record.

Then there's the idea that humanity is not so much hard, as different. Philosophers have spent many pages coming up with new ways of phrasing that point. Nature is material, but we're spiritual. Nature is in-itself, but we're for-itself. And so on. If we can understand the mind at all, it certainly won't be through reductionistic, mechanistic, rationalist, objectivist (phew) science, they say.

Again, this seems perfectly plausible... to us, now. But people used to say the same thing about living things in general. That was vitalism, the idea that physics and chemistry were fine for inert matter, but anything alive was radically different.

At a certain point in history, when biology was almost completely seperate from (and primitive compared to) the other sciences, that seemed fine. But it turned out to be wrong. With the benefit of hindsight. Nowadays, no-one sees a radically difference between nature and bacteria, plants or animals... well, except humans.

Maybe the mind will never be understood within the framework of the rest of science. I don't know, but I don't think anyone else does right now, either.

Today's LGBT History Month Icon: Ryan Murphy

New Documentary on Maine's Marriage Equality Vote

This looks quite good...

Today's LGBT History Month Icon: Constance McMillen

Generational Thinking

The Native American populations often looked nine generations ahead in their planning. In the following short video we see how this can be done with a structure that is not only strong but natural. A living bridge! If only we could see that our children are living bridges that connect us to the future. If only our leaders could see beyond the next election. If only our corporations could see beyond the next quarterly report...

Life With Low Serotonin, Revisited

Last year I covered the case of a young man born with a genetic disorder which caused him to suffer low levels of the monoamine neurotransmitters - serotonin, dopamine, and noradrenaline.

These are the chemicals that are widely thought to be deficient in depression, and they're the target of antidepressant drugs (especially serotonin).

If low monoamines cause depression, you'd expect someone with low monoamines to be depressed, at least on the simplest view. But the case from last year had no reported mood problems, although he did show appetite, sleep and concentration problems that were cured by serotonin replacement therapy.

Now a new case report has just appeared that tells a different story. Gabriella Horvath and colleagues from British Columbia describe two sisters. Both had a normal birth and childhood, but at the ages of 11 and 15 respectively, began to suffer severe migraines and other symptoms. Sister 1:

started having hemiplegic migraine at age 11 years, initially occurring every 3–8 weeks, lasting 4–48 hours, presenting with right or left-sided numbness and paralysis, no visual disturbances, but slurred speech, associated with vomiting, headache, and confusion, followed by weakness lasting up to 7 days, and then complete recovery. The frequency of her migraine increased slowly with age up to twice a month...

Between 12 and 20 years she had developed progressive spastic paraparesis; sensory loss in stocking distribution... urinary and bowel incontinence; bladder instability... irritable bowel syndrome; sleep problems; depressed mood; and anxiety. She needed to use a wheelchair for most of the time by the age of 17.

Sister 2 had a rather different course:

The older sister originally presented at the age of 15 years with a history of hemiplegic migraine and seizures and myoclonic jerks. EEG showed generalized spike-and-wave activity, and polyspikes with photoconvulsive [light-induced seizures] response, in keeping with juvenile myoclonic epilepsy. Her seizures were brief and infrequent and not associated with the migraine episodes...

She subsequently developed progressive weakness, frequent falls, depression, and mild bladder instability...

Various blood and genetic tests failed to get to the bottom of it. MRI scans showed abnormalities in the spinal cord and parts of the brainstem in both cases, but why?

Spinal tap studies in Sister 1 revealed very low levels of 5HIAA, which is a by-product of brain serotonin (5HT). This suggested low 5HT levels. So doctors started her on 5HTP to try to boost it.

They report that 5HTP treatment caused "improvement" in all symptoms, including the migraines, slurred speech, depression, and movement, but not immediately. She gradually went from being in a wheelchair to being able to walk around the house on crutches, although she used a wheelchair outside. However, after 3 years of treatment, at age 20, she suddenly fell into a coma lasting 2 months. She is now recovering.

Sister 2 also had low 5HIAA, and was given 5HTP. She also reported symptomatic improvement.

Blood tests reported very low platelet serotonin levels. 5HTP treatment increased this but they were still below normal. Platelet 5HT reuptake rate was also low, suggesting a problem with the 5HT reuptake transporter protein 5HTT.

But the 5HTT gene (famously known as "The Happiness Gene" although that's questionable) seemed entirely normal in these patients. The authors say however that the symptoms are, in some ways, reminiscent of mice who lack the 5HT reuptake protein (5HTT knockout mice), who also show low serotonin. Also, if it were genetic, that wouldn't explain why there were no problems at all during childhood.

So this case is a mystery. The low serotonin has no known cause, and it might just be a side effect of a deeper underlying problem, but serotonin has long been linked to migraines so it might account for some of the symptoms. The fact that 5HTP helped supports this, though it wasn't a controlled trial so we can't know for sure.

As for the depression and anxiety, improved by 5HTP, this could have been a result of low serotonin, but it could also have been a psychological reaction to the severe medical problems. It's impossible to know.

Horvath GA, Selby K, Poskitt K, Hyland K, Waters PJ, Coulter-Mackie M, & Stockler-Ipsiroglu SG (2011). Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin. Cephalalgia : an international journal of headache PMID: 22013141

The True Seat of Consciousness

(Alex Grey artwork)

I was recently asked -  what is going on in the world? What is happening to people that they seem so out of control and negative? Why are they so unhappy?

The question can be answered with one word - fear. People feel the changes happening in our world and without understanding what those changes might mean, they become fearful that it will mean loss. Loss of everything they have held dear - a way of life, job, house, car, money, security, health.

Their fear is not unfounded. Many people are facing loss. So how do we step outside of fear of loss? After all, everyone will experience it at some point.

I believe the only way to step back from fear is to learn to live from the heart, side stepping the mind - which is where fear lives, learning to live from the true seat of consciousness, which is the heart. (Remember - we grow out of a heart, not a brain.) This is not the sentimental heart in which we are familiar - soft, weak, reactive, feminine, sympathetic, needful. On the contrary, the heart of which I am speaking is empowered by the Creator. It is the vibrational point of equality, the original awareness - the place where individuality and Oneness occurs. It possesses uncommon intelligence, resilience, with the ability to flow and adapt. It is empowered, and is capable of unending compassion and love. This distinction is important.

So how do we access this heart?

First, we must have behavioral intelligence.

The first step is to have humility. Recognizing that we are no better or higher than any other human being. We were all created equal, and in that realization, everything changes.

Learn appreciation. Appreciation begins with recognizing the small things in life that make it full and abundant. That doesn't mean money or prestige, but appreciation of clean water, food, the air we breathe or the birds singing in the tree. It is the recognition of life itself. It is being mindful. Contentment with the mundane.

Practice compassion. Most of us are doing the best we can, although it doesn't always seem so. The best way to avoid being judgemental is to bless the person, place, or thing. It shifts the mind from negative to positive, and keeps you heart-centered.

Forgiveness and Understanding. Sometimes easier said than done. These two take practice. But when we learn to put ourselves in other people's shoes, we get a better understanding of where they may be coming from - which makes it easier to forgive.

And last but not least, we must be valiant in our efforts to do the right thing. Asking ourselves if it is the right thing to do - not always the easiest, or most gratifying, but the right thing can lead to the heart of a lion. Strong and fearless.


(Adapted from James the Wingmaker teachings. For more information go here.)

The Facebook Brain

Facebook friend tally is associated with differences in brain structure

People with lots of Facebook friends have denser grey matter in three regions of the brain, a study suggests

When I heard about this, my heart sank. The Facebook area of the brain? It had all the hallmarks of a piece of media neuro-nonsense: a hook (Facebook!), a simplistic neo-phrenological story (bigger brains are better!)... so I was expecting to discover that the fuss was all about some tiny, statistically questionable study, which wasn't really about what the newspapers said it was, as is so often the case.

So I was very surprised to find that it's actually an extremely good paper.

Kanai et al from London took 125 young Facebookers (mostly students) and correlated their friend count with grey matter density across the brain. They found some correlations:

The numbers seem solid. It was a large study. They used whole-brain correction for multiple comparisons (a=0.05 FWE corrected), controlling for age, gender and overall brain grey matter.

Most importantly, they included a replication sample, something that very few neuroscience papers do. After having done the first 125 people, they got another 40, and looked in the areas where they'd previously found results. They found the same correlation in all three cases - in fact, it was even stronger.

They even made sure to only display the scatterplots from the replication sample, thus avoiding the dreaded voodoo correlations problem that so often plagues such graphs. Note that the correlations are actually with the square root of the number of friends.

As if this wasn't enough, they confirmed a previously reported correlation between amygdala size and social network size, in both of their samples. And to cap it all, they show that Facebook friends are correlated (albeit not hugely) with other measures of number of friends.

So, as unlikely as it sounds, this Facebook finding is stronger than a good 90% of similar papers.

What does it mean that the size of the amygdala, left MTG, right STS and right entorhinal cortex are correlated with your Friend count? Good question. The authors discuss the result in terms of the known functions of these areas, e.g. the entorhinal cortex is involved in learning to associate pairs of stimuli, such as matching names to faces, which might be related to keeping track of your friends... but frankly this is just a post-hoc story.

You could tell an equally convincing tale about almost any part of the brain, if you found a correlation there. And as the authors point out, they didn't find correlations with other "social" areas you might expect like the mirror neuron system.

But that doesn't change the fact that the results of the study seem rock solid. So what's going on? It could be that having lots of friends makes your brain bigger. Or it could be the reverse, that having a certain kind of brain wins you friends, or at least Facebook ones. Or it could be that there's some third factor underlying the correlation, although who knows what that is.

Kanai, R., Bahrami, B., Roylance, R., & Rees, G. (2011). Online social network size is reflected in human brain structure Proceedings of the Royal Society B: Biological Sciences DOI: 10.1098/rspb.2011.1959

Today's LGBT History Month Icon: Michael Kirby

Ad Spotlight: Kimpton Hotels

Kimpton Hotels has launched a new website dedicated to communicating the various LGBT services and programs they offer, including LGBT marriages, ceremonies, honeymoons, parties, and events. Check it out here.

Today's LGBT History Month Icon: David Kato

What Is Brain "Activation" on fMRI?

Functional MRI is one of the most popular ways of measuring human brain activity. But what is "activity"?

Fundamentally, neural activity is electical potentials and chemical signals. fMRI doesn't measure these directly. Rather, it measures changes in the oxygen content of blood in different parts of the brain.

The more the brain cells are firing, the more oxygen they use up, although oxygenation actually increases as a kind of compensation for the activity and this increase is what gets measured. The oxygenation changes associated with neural firing is called the BOLD response.

Using fMRI you can measure BOLD and end up with some pretty blobs of activation. But what does it mean for a region of the brain to be activated? Just as no man is an island, no brain region can do anything on its own. Every area gets inputs from other areas, and sends outputs as well.

So if an area gets more active, that could mean one or more of three things:

1. It's sending more outputs
2. It's getting more inputs
3. It's doing more "internal" processing within that area - "talking to itself".

Which of these contributes to BOLD? It's known that number 1 - output from the area in question - is not a major contributor to the fMRI signal, but what about 2 and 3? A 2010 paper that I just came across argues that 80% of the BOLD signal is caused by internal processing, and only 20% is due to input.

They took some rats, and stimulated their whiskers. Using electrodes, they measured blood oxygenation changes in an area called the barrel cortex, which is known to deal with whisker-based sensations (they didn't actually use fMRI, but this would be seen as a BOLD signal if they had.)

But they then added a drug called muscimol to the barrel cortex. Muscimol reduces neuronal firing, but it doesn't affect synaptic input. They show that muscimol strongly reduced the blood oxygenation response, by about 80%. This suggests that 80% of the signal was not caused directly by sensory input to the cortex, but was generated within the cortex.

In many ways this is not surprising: it would be weird if the cortex were just picking up signals and doing nothing with them. However, it's good to be able to put a figure on just how much intra-cortical processing contributes to the fMRI signal. In rats, at any rate.

Harris S, Jones M, Zheng Y, & Berwick J (2010). Does neural input or processing play a greater role in the magnitude of neuroimaging signals? Frontiers in neuroenergetics, 2 PMID: 20740075

Little Life Lesson: Be Approachable

Today I made it a point to not have my headphones on while walking down the street. And I even slowed down from my usual hurried pace. The result? More people approached me. I recommended a restaurant to a gay brother and sister visiting Boystown from NYC, and later I met a hairstylist looking for work who just moved here from Oklahoma. These little encounters kind of made Chicago feel more warm and neighborly. Today I realized that Chicago never wasn't this way - I just wasn't approachable enough. That changes from here on out. 

Today's LGBT History Month Icon: Frida Kahlo

Secret History of the Global Collapse

Ever wonder how the global financial collapse actually happened? Who exactly are the people behind the scenes? I found this documentary on CMN, and from my personal research - this is how it went down.

With the world coming together and looking at solving these problems, it's a good idea to know the specifics of how it happened - so we can make sure it never happens again. We are lucky enough to be part of something really big. The stunned masses are beginning to stir, and history is being created. It won't happen overnight - but we outnumber the people who have run the show up until now. It's our turn.

Synchrosecrets did a wonderful post today on Indra's Net and how it relates to the Occupy Wall Street movement that is sweeping the world as we speak. One of the people commenting posted "Nine Commandments" that the Occupiers in London are using as their demands (at least some of them). I think they are perfect. What do you think?

1. The current system is unsustainable. It is undemocratic and unjust. We need alternatives; this is where we work towards them.

2. We are of all ethnicities, backgrounds, genders, generations, sexualities dis/abilities and faiths. We stand together with occupations all over the world.

3. We refuse to pay for the banks’ crisis.

4. We do not accept the cuts as either necessary or inevitable. We demand an end to global tax injustice and our democracy representing corporations instead of the people.

5. We want regulators to be genuinely independent of the industries they regulate.

6. We support the strike on the 30th November and the student action on the 9th November, and actions to defend our health services, welfare, education and employment, and to stop wars and arms dealing.

7. We want structural change towards authentic global equality. The world’s resources must go towards caring for people and the planet, not the military, corporate profits or the rich.

8. We stand in solidarity with the global oppressed and we call for an end to the actions of our government and others in causing this oppression.

9. This is what democracy looks like. Come and join us!

Living Fearlessly

Easier said than done. We are supposed to fear everything these days. The latest fear to hit our house is the vitamin scare. My husband, never a vitamin proponent, thinks I should fear my vitamins. After all, there is a new study somewhere that says vitamins may cause cancer. Well, I think fearing vitamins causing cancer, actually causes the cancer. Instead, I tell him, the pharmaceutical companies actually want to get a bill passed that would outlaw over-the-counter vitamins and require that we have to go to a doctor and get a Rx for our vitamins. Who do you suppose wins with that scenario?

We are being inundated with fear porn. I can't think of anything I'm just supposed to enjoy. So I'm consciously trying to shift my awareness to enjoying absolutely everything I can. If it's an icy cold Maker's Mark Manhattan served at our favorite restaurant, I'm going to thoroughly enjoy it! I know I'm not supposed to drink colored spirits, they're supposed to be bad for you, but I'm choosing instead to focus on what it is I like about that perfectly prepared luxury.

So when I came across this interview, I knew I was getting reinforcement that I'm heading in the right direction. It's time to live fearlessly. As Steve Jobs reminded us in his speech at Stanford University - "you have nothing to lose - you're already naked."

Placebos And The Brain's Own Pot

According to a neat little new paper, the placebo effect relies on the brain's own marijuana-like chemicals, endocannabinoids.

Or rather, some kinds of placebo effects involve endocannabinoids. It turns out that "the placebo effect" is not one thing.

The authors, led by Fabrizio Benedetti, have previously shown that placebo "opioids" - i.e. when you expect to get a painkiller such as morphine, but actually it's just water - relieve pain via the brain's own opioid system (endorphins). Blocking endorphins with certain drugs blocks the power of placebo morphine.

But there are many painkillers that aren't opioids, leaving open the question of whether all placebo effects on pain are mediated by endorphins.

The new study claims that endocannabinoids are involved in non-opioid placebo analgesia. They used rimonabant, a weight loss drug that was pulled from the market shortly after it appeared, because it caused depression. Rimonabant worked by blocking CB1 receptors, which are the main target of the psychoactive chemicals in cannabis - and also key players in the endogenous cannabinoid system.

Here's the headline result:

The graph on the left shows the relationship between the pain relieving power of morphine, and the pain relief caused by placebo "morphine" given on a subsequent day. As you can see, there was a strong correlation. People who had a strong response to real morphine, later responded well to the fake morphine. But rimonabant had no effect at all.

Pain relief was measured using tolerance to the pain caused by a tightly fitting tourniquet.

However, rimonabant did have a strong effect on the placebo response to a different drug, ketorolac, which is related to the better-known ibuprofen (Nurofen). As you can see in the graph on the right, people given rimonabant had a much lower response to the placebo "ketorolac".

In other experiments, they showed that rimonabant alone had no effect on pain tolerance.

This is a nice result. It shows that the placebo effect is not a single thing, but that it depends upon the nature of the drug that you believe you've got. It also reminds us that the placebo effect is not some magical power of mind-over-matter, but is in fact, well, matter-over-matter.

Interestingly, ketorolac has no effect on endocannabinoids, or at least no direct effect. The mechanism of action, which is fairly well understood, has nothing to do with cannabinoids. Yet placebo "ketorolac" still seems to set endocannabinoids buzzing.

Benedetti F, Amanzio M, Rosato R, & Blanchard C (2011). Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nature medicine, 17 (10), 1228-30 PMID: 21963514

Today's LGBT History Month Icon: Neil Patrick Harris

Can You Hear Us Now?

Dr. Kashonia from Australia has posted on Occupy Wallstreet and the worldwide effects she sees coming. She's posted several videos and does a good job explaining some of the organizations involved. Here is a song that I think speaks to many of us:

Today's LGBT History Month Icon: Lady Gaga

Mountains of Mental Disorders

This is a story about a man who lived in a house. Here it is:

The house was a lovely thatched cabin, situated in a wooded valley between two little hills, set against the spectacular scenary of a snow-capped mountain. He'd been born there, and he'd lived there all his life.

One day, there was a knock on the man's door. He opened it to find two official-looking people carrying clipboards, with serious expressions on their faces.

"Hello, sir. We are officials from the Ministry of Mountains. Sorry it took us so long."
"Oh... excuse me?", the man replied, puzzled.
"We're very sorry we didn't get here earlier."
"I'm afraid that I don't know what you mean. I wasn't expecting any..."
"Hmm. Let me explain. The Ministry of Mountains exists to help people who live on mountains. So, you see, we're here to..."
"Ask for directions to the mountain? It's about 10 miles down the road. Just look up - you can't miss it."

The official looked unamused.
"No. We're here to help you, sir."
"Help you to cope with the rigors of mountain living!" the other chimed in, helpfully.
"But... I don't live on a mountain."
"I'm afraid you do. Look - " and the first official unfolded a large map. "Do you agree that there is a mountain, here?" and she pointed to a spot 10 miles down the road.
"Yes. Actually I just told you about i..."
"...and, do you agree that you live - here?"
"Of course, but..."

"So you do live on the mountain. The very ground beneath our feet right now is part of that mountain nearby."
"No it's not." The man protested. "This is a valley, miles away. I mean just look outside. We're clearly not on a mountain now, are we?"
"How old fashioned. That's what we used to think. But, thanks to advances in geology, we now appreciate that these hills and valleys are merely a part of the mountain."
"Yes!" the other said, whipping out a textbook and becoming increasingly enthusiastic. "You see, a mountain is merely a mass of rock, and this rock extends underground for a considerable distance... It's impossible, really, to draw a line on the map and say categorically, this side is mountain, this isn't. So 'mountains' are an arbitrary construct. 'Hills' are likewise just protrusions of the underlying mountain and..."

The man was even more confused now. "Umm... well, I suppose, technically...but..."
"...so yes, so you do live on a mountain. And we know that this is very difficult. You're exposed to all kinds of dangers like blizzards, altitude sickness, avalanches..."
"Not really. It's nice here. It doesn't even snow most years."
"That's unlikely. You agree that mountains have blizzards and avalanches? Right. And you earlier agreed that there's no dividing line between you and a mountain. So logically..."
"Er..."
"So you are in danger! Don't worry, though. We're here to help. To start off with, we're going to reinforce your house with six tons of cement, to protect you against rockfalls. The construction crew will arrive tomorrow morning. Now, as for those blizzards..."
The man had had enough of this.
"This is absurd. Now look - there is a guy who really does live on top of the mountain in a rickety old shack. Old Grandpa McHermit. He might actually need your help. I don't. Get out! And if I see anyone with a bag of cement tomorrow morning, I'll shove it right up their..."

---

As you may have guess, this story is a metaphor. There is a movement in psychiatry at the moment, away from a 'categorical' view of mental illness towards a 'spectrum' view. Mental disorders are not things you either have or don't - defined according to some arbitrary cut-off. Rather, they're things that everyone has, to some degree.

This has already happened, or is happening, to autism, schizophrenia, bipolar disorder, personality disorders, and more.

Now, the "spectrum" or "dimensional" approach has much to recommend it. It's true that diagnostic cutoffs are arbitrary. It's true that the categorical approach doesn't capture the true degree of variation that real people display.

My worry is that these new "spectra" are, in practice, merely the old categories, just bigger. We still think of people as being ill or not-ill, although we may call it on the spectrum or off it. Worse, we still think of "ill" in the same way as we used to i.e. as referring to the most severe end of the spectrum. The only difference is that we've expanded the old category of "ill" to cover more people.

This is evident in the fact that we still use the old categorical labels. It's the autism (or schizophrenia or bipolar) spectrum, even though "autism", in the old sense of a discrete disorder, is now supposed to be just one extreme of that spectrum. Yet the point about an extreme is that it's unusual, so why call it that?

We don't call the rainbow the red spectrum. We don't call height the midget spectrum. We don't call hills part of the mountain spectrum.

The point is, we really think of color and height and altitude as spectra, not as approximations to an extreme point, and that's good, because they are. Now it might well be possible to think of autistic or bipolar traits in the same way - but not if we call them autistic and bipolar traits. And not if we just rename them, while keeping the mental associations the same.

Not unless we can find a way of referring to what's currently called the autism spectrum without making anyone think of autism when they hear it. Similarly for "bipolar" and all the rest. Until we get to that point, there's a real risk that "spectra" will just be big categories.

Edit: This post has been very kindly translated into Hebrew over at the alhasapa.com blog.

Today's LGBT History Month Icon: Denise Eger

Mental Illness And Creativity Revisited

A new study offers support for the theory that mental illness is associated with "creative" achievement.

The idea that madness is close to creative genius is a popular one. From the nutty professor to the tortured genius, there's no end of sterotypes, and pop culture seemingly offers plenty of examples, from Van Gogh and his ear to Charlie Sheen and his bi-winning.

But is it true?

A new study says yes. Kyaga et al looked at everyone in Sweden who had been treated as an inpatient for either schizophrenia, bipolar disorder, or depression, between 1973 and 2003. In total that meant about 300,000 people (two thirds of that was depression).

They then matched this up with the Swedish national census which asks people their occupation. They looked to see whether the psychiatric cases were more likely to have been employed in a "creative" profession. They defined that as visual artists (photographers, designers, etc.) non-visual artists (musicians, actors, authors) and academics (university teachers).

Finally, they pulled up the records on the patients' relatives, to see what their jobs were. This is one of those studies that could only happen in Scandinavia, because only those countries keep such comprehensive ( rather scarily so) info about their citizens.

They found that being bipolar, or being a close relative of someone who's bipolar, was associated with having a creative job. For schizophrenia, the picture was more complex: being a schizophrenia inpatient was not linked to being a creative in itself, but being related to someone with schizophrenia was. The effects were fairly modest.

For depression (not bipolar, just plain unipolar depression), there was no link at all, or even a slightly lower level.

The correlation wasn't driven by differences in IQ (yes, they had data on that too, for males, thanks to military service records.) Creative types had higher IQs on average while psych inpatients had slightly lower IQs than others. So correcting for IQ made the associations even stronger.

So it looks as though being bipolar, at any rate, is linked to creativity, and so is having bipolar and schizophrenia in the family - if you believe these findings. Should we?

This study was huge and the data are, on the face of it, very comprehensive. However, it turns out that many people didn't state their occupation, especially the patients. Only 45% of people with schizophrenia gave a valid answer, compared to 75% of the bipolar and depressed. In the controls, it was about 80%.

That's a serious issue. The authors did try to get around this by looking at the siblings of the patients with missing data. For schizophrenia, siblings of missing data schizophrenics were more creative than for the ones with full data, and for bipolar there was no difference. So the effects are not due to nonreporting of non-creative jobs.

Another possible confound is family background and environment. Indeed, the fact that people with bipolar were no more likely to be in a creative job than their relatives who weren't bipolar (or, at least, never received inpatient treatment) rather supports this view. Maybe the relatives shared genes with the patients meaning that their creativity was associated with bipolar, but we can't know that.

One reassuring piece of evidence against the idea that these results were driven by a general correlation between psychiatric hospitalization and "middle class professions" is that there was no association with the "non-creative" job of accountancy and auditing (sorry accountants and auditors).

Overall, while this is an interesting study, and while I find the proposed link between mental illness and creativity plausible, we need more detailed research to ensure that the correlation isn't just a reflection of socioeconomic factors.

Kyaga, S., Lichtenstein, P., Boman, M., Hultman, C., Langstrom, N. Landen, M. (2011). Creativity and mental disorder: family study of 300 000 people with severe mental disorder The British Journal of Psychiatry DOI: 10.1192/bjp.bp.110.085316

Our Little Angel

You may remember my posts here and here about my great niece, Lilly. She is a very special little girl. She is fighting the fight of her life right now and needs your prayers and positive energy. Please take a moment in your day and send her love and light. We know it makes a difference.

She came off the respirator today, but is still in ICU, so it is still touch and go, minute by minute. Her heart stopped earlier this week, and her mother literally saved her life.

If you can help by becoming a bone-marrow donor, or have a few dollars to send her single mother, here is the website for Team Lillian. 

Thanks everyone, I really appreciate it.

Thank you to Hilary for Post Of The Week:

Today's LGBT History Month Icon: Alan Cumming

Ad Spotlight: Bevan Duffy's New Campaign Ad Features His Daughter

Bevan Dufty, who is running for mayor of San Francisco, recently released a TV commercial featuring his daughter Sidney, who he conceived with a lesbian friend. Some are saying the ad is exploitative, but I discredit that criticism as a double-standard. Conservative politicians feature their families in political ads all the time - usually in the name of "family values." I think it's nice to see a positive representation of a nontraditional family in a campaign ad. 

Today's LGBT History Month Icon: Aaron Copland

The Winds of Change

For anyone who is still in the dark about Occupy Wall Street, or the Arab Spring, here is a great article. This man took many of my thoughts and organized them into a thoughtful and substantive essay. We are in a time of correction. The world is wildly out of balance. We're literally killing ourselves and our planet, and now we need to try and fix it.

We're never going back to an economy driven by insatiable appetites for stuff bought with debt. We're over that. It's time for our economists to start thinking of a new paradigm. We're the 99%'ers, and even if we're doing okay in this economy, all we have to do is look around to confirm the inequity. We're at the end of a monetary system that excludes 99% of its population. One that indebts its children for years, just for an education. Or takes the elderly person's home to pay for healthcare. Our systems are failing us.

Time for our politicians to hop on board, or move aside. After all, they're supposed to be working for us - not the next big corporate donor.

A new wind is blowing. It is the wind of change, and it will not be stopped. It's time to start designing a new world based on unity and fairness, one that supersedes borders and boundaries, having nothing to do with religion, race, culture, or color. Where all people, everywhere, are important and matter. A world that is grateful,appreciative, and respectful of its home planet. Nothing less will do.

So, put on your thinking cap. I think we're going to need it.