Archive for the ‘psychiatry’ Category

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?



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Is it possible to identify a psychiatric disorder using a structural brain scan? According to a team of researchers from Europe and Australia this can indeed be the case. In a recently published study in NeuroImage, researchers Carles Soriano-Mas et al. demonstrate that structural brain scans can identify subjects suffering from obsessive-compulsive disorder (OCD) with a 93.1% classification accuracy (for a whole-brain comparison). In addition, individual variance in OCD symptom severity was correlated with the measured neural differences. In other words, the more you suffer from OCD the more you are likely to stick out in the analysis as an oddball, compared to a healthy norm.

Here is an image showing the structural differences between OCD patiens (n=72) and healthy controls (n=72):


In the image, the heat scale indicates regions where OCD patients differ significantly from controls at the whole brain level. Interestingly, when the researchers focused on the most intense regions the predictive value of the brain scans dropped to 76.6% accuracy. This means that a whole-brain approach is the optimal for determining whether a subject is suffering from OCD.

The study clearly demonstrates that neuroscience is moving in the direction of single-subject analysis, and the application of advanced analysis methods to determine whether a given individual is structurally (or functionally) within the normal range. If the means are there, when will we see them being used — and misused? After all, if a brain scan has the close to 100% accuracy of telling whether a person is suffering from OCD, why not use it in the clinic right away? Or better, why not expect applicants to an important company position take such a scan? After all, if you suffer from OCD, you are less likely to be able to be in such a position, right? And while we’re at it, why not try for a similar approach for depression, anxiety, stress and introversion?

Are we right in being sceptical towards the application of such measures of psychic health? Methodological problems aside, should such a measure provide a robust assessment tool, why should we not use it? After all, psychological testing is really aimed at uncovering who people are. Apply for a top position and you are likely to be submitted to psychological and cognitive profiling. If scanners provide a better accuracy, would it not be preferable to use this method? Since society has decided to allow psychological and IQ testing, such measures should really be just another improved method. As a consequence, we should not be surprised to see them being used pretty soon — if they are not already in the stores.

The solutions are far from clear in the muddy waters following the blazing trail of neuroscience. As neuroscientific methods move along and create new opportunities, new problems arise, too. What is important is to bring these issues up front in the media and other forums of such debate. Neuroethics is as important as ever.

– Thomas

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brain_child_by_temabina.jpgIt’s really a slow digestion period, getting back from SfN in Atlanta. Other than an aching back and jet-lag the conference experience has been tremendous. But at the same time it was rather confusing. Those talks and lectures that I expected to be good turned out to be boring or far too complex (or ill presented) to comprehend. Other talks — IMO wildcards relative to my own area — were tremendously informative.

It strikes me that this year didn’t have one or more major themes that were dominating the discussion and themes as such. This very much as we’ve seen in previous conferences, and at other conferences, where topics such as e.g. stem cell research (SfN) or brain development or imaging genetics (Human Brain Mapping) was on everybody’s lips. So while I sit here back home and reflect on some highlights — other than those very technical aspects that I myself found interesting — a few come to mind.


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mysticfigure.jpgA new report in Nature demonstrates that electrical stimulation of the temporoparietal junction in the brain induces a sensation of the presence of an illusory “shadowy person”. One of the hallmarks of certain forms of schizophrenia is just this phenomenon: the eery feeling of someone’s presence. Now, it has been demonstrated in a study using electrical brain activation in a person without a history of psychiatric problems.

Basically, the study was performed on a subject that was at the preoperative stage of surgery for epilepsy. A normal procedure is to anaesthesize the patient before opening the skull, and then wake the patient up before stimulating the brain. The aim of such stimulation is to find the location of epilepsy onset, as well as to stimulate the areas surrounding this region, in order to map functionally important regions (e.g. language that are important in language). Such preoperative procedures are known to lead to a better surgical sensitivity, i.e. the ability to remove all of the abnormal tissue, and a higher surgical selectivity, i.e. avoding removal of normal tissue. In this way, neurosurgeons often evoke a number of sensations and behaviours in patients, including the disruption of speech, visual phosphenes, and memory deficits.

In the present case, the neurosurgeons found that electrical stimulation lead to a feeling of the presence of another person. Moreover, the patient reported that this figure was taking the same posture as herself, and even sometimes interfering with a task she was performing:

When stimulated (…) the patient had the impression that somebody was behind her. Further stimulation induced the same experience, with the patient describing the “person” as young and of indeterminate sex, a “shadow” who did not speak or move, and whose position beneath her back was identical to her own (“He is behind me, almost at my body, but I do not feel it”). (…) Further stimulations [other location] were applied while the seated patient performed a naming (language-testing) task using a card held in her right hand: she again reported the presence of the sitting “person”, this time displaced behind her to her right and attempting to interfere with the execution of her task (“He wants to take the card”; “He doesn’t want me to read”).

Stimulation of the temporoparietal junction (shown with an arrow in the image above) thus seems to distort some kind of body image, or maybe even efference copy (PDF) of self-actions. Both functions that are dramatically affected in abnormal brain states following certain kinds of delusional schizoprenia and brain injury.

The finding also nicely relates to the Swiss group’s earlier study combining EEG, TMS and the study of an epilepsy patient, where it was found that disruption of the temporoparietal junction function led to an “impaired mental transformation of one’s own body”. Here, the researchers concluded that:

the [temporoparietal junction, TPJ] is a crucial structure for the conscious experience of the normal self, mediating spatial unity of self and body, and also suggest that impaired processing at the TPJ may lead to pathological selves such as [out-of-body experience].

Here is the full story:

Induction of an illusory shadow person
By Arzy et al
Nature 443, 287

Stimulation of a site on the brain’s left hemisphere prompts the creepy feeling that somebody is close by.

The strange sensation that somebody is nearby when no one is actually present has been described by psychiatric and neurological patients, as well as by healthy subjects, but it is not understood how the illusion is triggered by the brain1, 2. Here we describe the repeated induction of this sensation in a patient who was undergoing presurgical evaluation for epilepsy treatment, as a result of focal electrical stimulation of the left temporoparietal junction: the illusory person closely ‘shadowed’ changes in the patient’s body position and posture. These perceptions may have been due to a disturbance in the multisensory processing of body and self at the temporoparietal junction.
Top of page

1. Laboratory of Cognitive Neuroscience, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
2. Presurgical Epilepsy Evaluation Unit, University Hospital, Geneva 1211, Switzerland
3. Department of Neurology, University Hospital, Geneva 1211, Switzerland
4. Center for Cognitive Neuroscience, Dartmouth College, Dartmouth, New Hampshire 03755, USA


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gal507.jpgThe 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 15th and 16th, 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


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beer.jpgAs noted in my previous post, the impact of alcohol on brain maturation in adolescence is still considered an open question, although studies indicate that early exposure to alcohol is even more damaging in adolescence than in adulthood. It’s not surprising at all. Alcohol crosses the blood-brain barrier to influence the function of neurons. Actually, influence is not the right term: intoxicates or poisons the brain is more correct. After all, the effect of alcohol on your state of mind is due to a state of intoxication.Alcohol is of course only one of many substances that have an impact on brain function, and that are used for recreational purposes. Other psychoactive substances include nicotine/tobacco, cannabis, cocaine and LSD. In a population of adolescents the young vary in their use of such drugs, both the debut, the regularity of use, and the combined – or polydrug – use. The question is, then, what causes this variation?

In a special issue of Behavioral Genetics the genetic and environmental causes of substance use are explored and reviewed. For example, Jason Pagan and colleagues study the causes of alcohol use in adolescence, and conclude that

(…) there was no significant evidence of shared environmental influences on alcohol problems in early adulthood. Problems were largely influenced by genetic factors that overlapped with genetic influences on frequency of use. Unique environmental factors were largely specific to each stage, with some overlap between alcohol problems and frequency of use at age 25.
Danielle Dick and her colleagues, on the other hand, find that a specific gene, GABRA2, shows two specific patterns in relation to adolescent and adult alcohol abuse. First they found that aconsistent elevation in risk for alcohol dependence associated with GABRA2 is not evident until the mid-20s and then remains throughout adulthood. On the other hand, GABRA2 was also associated with other drug dependence in their sample, both in adolescence and adulthood. So this gene can indeed be a causative factor in the forming of drug use in general, which some findings seem to indicate. GABRA2 has been shown several times to be coupled to alcoholism. For example, Danielle Dick herself has published data showing a complex relationship between martial status, alcohol dependence and GABRA2, concluding in another publication this year:

These analyses provide evidence of both gene-environment correlation and gene-environment interaction associated with GABRA2, marital status, and alcohol dependence. They illustrate the complex pathways by which genotype and environmental risk factors act and interact to influence alcohol dependence and challenge traditional conceptualizations of “environmental” risk factors.
Anyway, the special issue in Behavior Genetics has several good articles on the gene-environment interaction effects on the development of substance use disorders. It’s a must-read to anyone interested in genes, brain and behaviour.


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Avshalom Caspi and Terrie Moffitt [interview with Moffitt here on npr] made quite a splash in 2002 when they published the paper “Role of Genotype in the Cycle of Violence in Maltreated Children” in Science. They reported that maltreated children would differ in the development of antisocial personality and violent behaviour depending upon whether or not their genotype conferred high or low levels of MAOA expression, a neurotransmitter-metabolizing enzyme. Thus, Caspi and Moffitt showed that a genetic variation may moderate the influence of environmental factors on behaviour in a rather dramatic manner, fueling the growing suspicion that the old nature/nurture dichotomy is much too simplistic. Behaviour is most probably not determined by either an innate genetic Bauplan or the ever changing forces of our surroundings. In Caspi and Moffitt’s study, at least, children with a low-level MAOA genotype only developed an antisocial personality if maltreated (if you happen not to be maltreated, a low-level MAOA polymorphism will not cause you to develop an antisocial personality); but, at the same time, maltreatment doesn’t affect children with a high-level MAOA polymorphism, so the maltreatment is not a cause in itself either. Genes and environmental factors interact to produce behaviour, and the real question is how they do so.

In the July issue of Nature Reviews Neuroscience Caspi and Moffitt discuss some important implications of their research. First of all, if you wish to understand how external pathogens can influence the brain, as is all-important for psychiatric treatment, you have to factor in the individual person’s genetic make-up. The ability of environmental factors to alter the nervous system and generate a disordered mind variates with genetic differences at the DNA sequence level. Say Caspi and Moffitt:

Heterogeneity of response characterizes all known environmental risk factorsfor psychopathology, including even the most overwhelming of traumas. Such response heterogeneity is associated with pre-existing individual differences in temperament, personality, cognition and autonomic physiology, all of which are known to be under genetic influence16. The hypothesis of genetic moderation implies that differences between individuals, originating in the DNA sequence, bring about differences between individuals in their resilience or vulnerability to the environmental causes of many pathological conditions of the mind and body.

Secondly, to really understand this interaction of genes and environmental risk factors and pathogens, more epidemiological cohort studies must integrate neuroscience measurements. As Caspi and Moffitt observe:

First, evidence is needed about which neural substrate is involved in the disorder. Second, evidence is
needed that an environmental cause of the disorder has effects on variables indexing the same neural substrate. Third, evidence is needed that a candidate gene has functional effects on variables indexing that same neural substrate. It is this convergence of environmental and genotypic effects within the same neural substrate that allows for the possibility of gene–environment interactions. At present, such evidence concerning environmental and genotypic effects in relation to neural substrate measures is sparse, and therefore gene–environment interaction hypotheses are likely to be circumstantial at best, and flimsy at worst. But this situation is steadily improving. When we were constructing our hypothesis regarding the genetic moderation of the depressogenic effects of stressful life events, we were aided by direct evidence linking the 5-HTT candidate gene to individual differences in physiological responsiveness to stress conditions in three different experimental paradigms, including knockout mice, stress-reared rhesus macaques and human functional brain imaging.

Of course, imaging genomics studies, such as those by Hariri and Weinberger, or Meyer-Lindenberg, give a good idea of how genetics, brain activity and behaviour can be related to each other, using avant-garde research techniques.

Finally, both perhaps most intriguing, Caspi and Moffitt suggest that findings such as theirs indicate that genes react to environmental influences more than cause brain activity and behaviour. This stance is captured in a quote like this one:

[The] gene–environment interaction approach differs fundamentally from the ‘main-effect approaches’,
with regard to the assumptions about the causes of psychiatric disorders. Main effect approaches assume that genes cause disorder, an assumption carried forward from early work that identified single-gene causes of rare Mendelian conditions. By contrast, the gene–environment interaction approach assumes that environmental
pathogens cause disorder, and that genes influence susceptibility to pathogens. In contrast to main-effect studies, there is no necessary expectation of a direct gene-to-behaviour association in the absence of the environmental pathogen.

Clearly, as such experimental work in greater detail furnish us with a more precise view of genes build the molecular structure of the brain, and how these structures underlie behaviour, we will also become better suited to settle long standing philosophical issues, such as what innateness actually is.


Caspi, A. & Moffitt, T. (2006): Gene-environment interactions in psychiatry: joining forces with neuroscience. Nature Reviews Neuroscience 7: 583-590.


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