Serotonin and value-based decision making

Can antidepressive medicine alter your decision behaviour? A recent paper in Science now demonstrates that alterations in subjects’ serotonin levels leads to significant changes in their decision making behaviour. In the study, subjects were set to play the Ultimatum Game repeatedly. Subjects had to do the task two times at two different days, and at one of the days they were administered an acute tryptophan depletion (ATD), i.e., their serotonin levels would drop for a period of time. The design was double-blind and placebo controlled.

The Ultimatum Game is an experimental economics game in which two players interact to decide how to divide a sum of money that is given to them. The first player proposes how to divide the sum between themselves, and the second player can either accept or reject this proposal. If the second player rejects, neither player receives anything. If the second player accepts, the money is split according to the proposal. The game is played only once, and anonymously, so that reciprocation is not an issue.

What the researchers found was that the ATD led subjects to reject more offers, but only unfair offers. That is, ATD did not interact with offer size per se, and there was no change in mood, fairness judgement, basic reward processing or response inhibition. So serotonin seemed to affect aversive reactions to unfair offers.

The study is a nice illustration of how we now are learning to induce alterations in preferences and decision making. Along with other studies using, e.g., oxytocin to increase trust in economic games (see also my previous post about this experiment), one may expect that increasing the serotonin level may actually make subjects less responsive to unfair offers.

This knowledge is also important to learn more about, as it poses a wide range of ethical problems. If our preferences and decisions are really influenced by these stimuli, can this be abused? It should be mentioned that many of these substances are not necessarily detected (oxytocin is odourless), so we may be influenced without our consent or knowledge. The wide applicances could include casinos, stores (e.g. for expensive cars), dating agencies and so on. If we did not accept subliminal messages in ads, how can we accept this?

-Thomas

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Oxytocin is the window to the soul

Research on the role of oxytocin, a neuropeptide, in social cognition has generated much interest during the last few years. We have earlier written about oxytocin’s role in social attachment; together with vasopressin, another neuropeptide, oxytocin is thought to be critical for linking social signals to structures in the mesolimbic part of the brain responsible for forming social attachment and pair bonding. In a study published in Nature Ernst Fehr and his group demonstrated that injecting people with a spray of oxytocin increases trust.

Now, in a pretty remarkable new study published in Biological Psychiatry, German researchers show that injecting subjects with a whiff of oxytocin will also improve be ability to infer, based just on eye cues, what a person is thinking about. Here’s the abstract:

Background

The ability to “read the mind” of other individuals, that is, to infer their mental state by interpreting subtle social cues, is indispensable in human social interaction. The neuropeptide oxytocin plays a central role in social approach behavior in nonhuman mammals.

Methods

In a double-blind, placebo-controlled, within-subject design, 30 healthy male volunteers were tested for their ability to infer the affective mental state of others using the Reading the Mind in the Eyes Test (RMET) after intranasal administration of 24 IU oxytocin.

Results

Oxytocin improved performance on the RMET compared with placebo. This effect was pronounced for difficult compared with easy items.

Conclusions

Our data suggest that oxytocin improves the ability to infer the mental state of others from social cues of the eye region. Oxytocin might play a role in the pathogenesis of autism spectrum disorder, which is characterized by severe social impairment.

Clearly, this suggests that oxytocin not only modulates mesolimbic brain structures. Earlier studies have implicated the fusiform face area and superior temporal sulcus in extracting social information from facial perception. May oxytocin also impact on these structures? Whatever turns out to be the case, I imagine that no politician or CEO will ever sit down at the negotiation table again without their trusty bottle of oxytocin.

-Martin

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Next Im-Gen meeting

The next International Imaging Genetics Conference is opening its doors now for registration. The third year in a row, building on two successful conferences, this third meeting will also house two separate workshops: one on brain imaging for geneticists; and one on genetics for brain imagers. All in the spirit of crossing the bridge between genetics, brain imaging and statistics. As this course was brilliant last year, I’m hoping to attend in January 2007, too.

Here is the announcement:

The First and Second International Imaging Genetics Conferences were held to bring together national and international experts in neuroimaging, genetics, data-mining, visualization and statistics. Targeting physicians and scientific researchers, this annual conference features presentations from investigators world-wide and held in-depth discussions within the emerging field of Imaging Genetics. Given the known importance of both genetics and environment in brain function, and the role of neuroimaging in revealing brain dysfunction, the synergism of integrating genetics with brain imaging will fundamentally change our understanding of human brain function in disease. To fully realize the promise of this synergy, we must develop novel analytic, statistical, and visualization techniques for this new field.

This international symposium was held to initially assess the state of the art in the various established fields of genetics and imaging, and to facilitate the transdisciplinary fusion needed to optimize the development of the emerging field of Imaging Genetics. The Third Annual International Imaging Genetics Conference will be held on January 15^th and 16^th, 2007 at the Beckman Center of the National Academy of Sciences in Irvine, CA. We look forward to seeing you at this exciting upcoming event.

Monday January 15th:

• Nicholas Schork, UCSD “Multivariate Analysis of Combined Imaging and Genomic Data”
• Eleazer Eskin, UCSD “Analysis of Complex Traits Through Intermediate Phenotypes.”
• Tom Nichols, University of Michigan “Statistical Challenges & Opportunities in Imaging Genetics”
• Fabio Macciardi, University of Toronto “Integrating Imaging Genetics Methods in Schizophrenia.”
• David Goldman, NIAAA “Genes and Neurobiologies in the Addictions”
• David Goldstein, Duke Institute for Genome Sciences and Policy “Neuropsychiatric pharmacogenetics”
• Daniel Weinberger, NIMH/NIH: TBA

Tuesday January 16th:

• Joseph Callicott, NIMH “Does risk for schizophrenia arise from multiple genes in vulnerable pathways? Evidence from DISC1 and FEZ1”
• Lisa Eyler, UCSD “Genetics of Brain and Cognition: A Twin Study of Aging”
• Fei Wang, Peking University “Neuregulin 1 Genetic Variation and anterior cingulum integrity in schizophrenia and in health.”
• Andreas Meyer-Lindenberg, NIMH/NIH “Genetic characterization of prefrontal-subcortical interactions in humans.”

**New for 2007** Sunday January 14th:

*** Half-day Workshop tutorials will be offered the day before the conference at the Beckman Center- see website for details***

Workshop 1: What Geneticists need to know about Brain Imaging
Workshop 2: What Brain Imagers need to know about Genetics

Registration and conference information can be found at the conference website

-Thomas

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CIMBI alive

The Center for Integrated Molecular Brain Imaging (CIMBI) is now officially opened. The overall idea behind this massive project is to study cognitive, psychological and biological phenomena with a multi-modal approach, combining data from genotyping, PET scanning and MRI scanning. The main project of CIMBI is to study “the neural bases of personality dimensions that predispose individuals to affective and substance use disorders, with special emphasis on the serotonergic neurotransmitter system”. In other words: to study the biological mechanisms behind personality formation. They are currently recruiting (and looking for) the best-qualified personnel for the new available positions.

One part of the CIMBI project involves looking at how genes coding for seretonin affect the seretonin transport function, and furthermore how the function of seretonergic areas of the brain operate depending on the genetic makeup of a subject. In this latter part, I am involved in doing the MRI study, including three fMRI protocols:

1. Processing of facial affect – how genes affect the processing of facial expression, especially the difference between aversive and neutral faces.
2. Memory processing in the medial temporal lobe (MTL) – how different parts of the MTL make different contribution to specific phases in memory processing: preparation, encoding, rehearsal and retrieval.
3. Categorization task – the difference between choosing between high-specificity options (within-category choices, e.g. “donkey or zebra”) or low-specificity options (between-category choices, e.g. “living or non-living”)

Data will be combined between fMRI (BOLD and perfusion), genotype and seretonine function as measured with PET. In addition we are looking at the relative contribution of changes in volume and form of MTL areas to the overall signal differences found in other modalities.

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Nalmafene for your ludomania

I have mentioned this as a headline at SCR. A new study demonstrates that Nalmefene, an experimental drug, has positive treatment effects on compulsive gambling. It works through making gambling become less thrilling and compelling. Maybe we can soon find a drug that makes statistics lectures more exciting, too?

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Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling.

by Grant et al. in Am J Psychiatry. 2006 Feb ; 163(2): 303-12

OBJECTIVE: Pathological gambling is a disabling disorder experienced by approximately 1%-2% of adults and for which there are few empirically validated treatments. The authors examined the efficacy and tolerability of the opioid antagonist nalmefene in the treatment of adults with pathological gambling.

METHOD: A 16-week, randomized, dose-ranging, double-blind, placebo-controlled trial was conducted at 15 outpatient treatment centers across the United States between March 2002 and April 2003. Two hundred seven persons with DSM-IV pathological gambling were randomly assigned to receive nalmefene (25 mg/day, 50 mg/day, or 100 mg/day) or placebo. Scores on the primary outcome measure (Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling) were analyzed by using a linear mixed-effects model.

RESULTS: Estimated regression coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had significantly different scores on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling, compared to the placebo group. A total of 59.2% of the subjects who received 25 mg/day of nalmefene were rated as “much improved” or “very much improved” at the last evaluation, compared to 34.0% of those who received placebo. Adverse experiences included nausea, dizziness, and insomnia.

CONCLUSIONS: Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) appeared efficacious and was associated with few adverse events. Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects.

HubMed (cache)

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See also this story in The Nation

Drug Shows Promise in Curbing Compulsive Gambling, Study Says

By Robert Lee Hotz in The Nation

For the estimated 6 million compulsive gamblers in the U.S., the long odds are on a pill.

In the largest clinical study of its kind, researchers at the University of Minnesota found that daily doses of an experimental drug called nalmefene, often used to treat alcoholism, appeared to curb the craving to gamble.

ADVERTISEMENT

The research represents the latest effort to control the biology of misbehavior at a time when celebrity poker, online gambling, lotteries and sports betting have helped to make obsessive wagering a national psychiatric disorder.

“The study is part of emerging evidence that gambling, once thought to be a problem in moral integrity, is instead a problem in brain biology and can be successfully treated,” said Dr. Robert Freedman, editor of the American Journal of Psychiatry, which published the study today in its February issue.

(…)

The Nation

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Mind Wars!

In the wake of my post yesterday about US government attempts to build a workable lie detector for use in the war on terror, here is an article about Jonathan Moreno, bioethics adviser for the Howard Hughes Medical Institute, who has a book coming out later this year entitled Mind Wars: National Security and the Brain. A little teaser from the article:

One of the leaders in neuroscience development is the corporation DARPA, which is currently in the process of developing a “head web,” a helmet that conducts non-invasive brain monitoring that could be used to measure brain waves while soldiers are in combat. Moreno said the government is also working on developing a “war fighter”-a human manipulated by drugs to be a more efficient soldier. The “war fighter” would require less sleep, less protein and could heal itself with the aid of drugs and technology. The war fighters would eventually be replaced by robots, which would be controlled by human soldiers in a bunker somewhere out of harm’s way. “We are probably moving to a cyborg technology,” Moreno said, and one of the first steps toward a more robotic world is the use of neurologically manipulative drugs, like the “anti-conscience pill,” which can treat stress, reduce guilt and potentially eliminate entire memories, preventing psychological conditions like post-traumatic stress disorder.

Says Moreno:

“I don’t think the government will control our brains in the old-fashioned, ‘Manchurian Candidate’ sense, but we will eventually be able to change our brains.”

I found the link to the article at the excellent Neuromarketing Blog.

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