Sunday, June 27, 2010

Creativity and mental illness

The association between creativity and mental illness is sort of a cliché – but that doesn't mean there's nothing to it. Standard examples given include Vincent van Gogh, Robert Lowell, and John Nash.

There has been a rather large amount of research into the connection, and a large number of biographical accounts of famous creative people who also suffered from mental illness. But the neurobiological details are emerging only slowly. After all, our understanding of the biological roots of either creativity or mental illness remains fairly rudimentary.

However, one recent study does add some tantalizing clues.

Thinking Outside a Less Intact Box: Thalamic Dopamine D2 Receptor Densities Are Negatively Related to Psychometric Creativity in Healthy Individuals
Several lines of evidence support that dopaminergic neurotransmission plays a role in creative thought and behavior. Here, we investigated the relationship between creative ability and dopamine D2 receptor expression in healthy individuals, with a focus on regions where aberrations in dopaminergic function have previously been associated with psychotic symptoms and a genetic liability to schizophrenia. Scores on divergent thinking tests (Inventiveness battery, Berliner Intelligenz Struktur Test) were correlated with regional D2 receptor densities, as measured by Positron Emission Tomography, and the radioligands [11C]raclopride and [11C]FLB 457. The results show a negative correlation between divergent thinking scores and D2 density in the thalamus, also when controlling for age and general cognitive ability. Hence, the results demonstrate that the D2 receptor system, and specifically thalamic function, is important for creative performance, and may be one crucial link between creativity and psychopathology. We suggest that decreased D2 receptor densities in the thalamus lower thalamic gating thresholds, thus increasing thalamocortical information flow. In healthy individuals, who do not suffer from the detrimental effects of psychiatric disease, this may increase performance on divergent thinking tests. In combination with the cognitive functions of higher order cortical networks, this could constitute a basis for the generative and selective processes that underlie real life creativity.

Executive summary: There is a correlation between performance on a part of a common psychological test for creativity and a certain property of neurons in a brain structure called the thalamus. The association with mental illness, specifically schizophrenia, is that the same neural abnormality in the same part of the brain has also been found to correlate with various symptoms of schizophrenia.

Let's look at creativity first. It's often defined, to quote from the research paper, as "the ability to produce work that is at the same time novel and meaningful, as opposed to trivial or bizarre". A creative work should be original and unexpected, but it should also be more than just randomly different from the ordinary. It should also impress us as insightful or solve a difficult problem.

So there are several abilities a creative person should possess. They don't necessarily correlate with each other, but all or most should be present for "true" creativity. A creative artist, for instance, should be inventive and original, but also have good artistic skills. As far as the present research is concerned, we're dealing just with the aspect of creativity that comprises novelty and originality.

The psychological test used in this research is called the "Berliner Intelligenz Struktur Test". It's a general intelligence test, and it consists of several parts. One part is the "Inventiveness battery", and the specific ability that measures is called "divergent thinking".

Even within the divergent thinking component, several characteristics can be distinguished. The test may ask, for example, to think of as many reasonable uses as possible for an object like a brick. The characteristics that might be observed include:
Fluency–the number of valid responses; Originality–how frequent the participant's responses were among the responses of the rest of the sample; Flexibility–the number of semantic categories produced; Switching–the number of shifts between semantic categories; and Elaboration–how extensive each response is (if the task involves producing more than single words).

To do well on this test, a subject must be able to quickly produce valid responses that are unobvious and diverse in nature, not just variations on a few themes.

Previous research had established that divergent thinking is influenced by the "dopaminergic" neural system, i. e., neurons whose primary neurotransmitter is dopamine. Specifically, there is a correlation between divergent thinking (as measured by the test just described) and certain variants of the dopamine D2 receptor. The present research further narrows down the relationship.

We've discussed dopamine before (list). It is involved in quite an impressive number and diversity of psychological phenomena, including appetite, addiction, risk-taking, memory, and trust. Some abnormalities of the dopaminergic system are also implicated in pathologies such as ADHD, Parkinson's disease, depression, and schizophrenia (dum-da-dum-dum).

Indeed, because dopamine is involved in so many functions, therapies for certain dopamine-related disorders can cause side effects in seemingly unrelated areas. For example, Parkinson's disease results from insufficient dopamine activity, but treatments that raise dopamine levels can cause other problems, such as pathological gambling, compulsive shopping, binge eating and other impulse control disorders. (Ref.: here.)

The reason that dopaminergic neuron abnormalities have such diverse effects is that dopaminergic neurons are common in a number of specialized areas of the brain. A dopamine abnormality will therefore affect whatever function such an area is involved in.

As far as divergent thinking is concerned, there are two brain areas of particular interest: the striatum and thalamus. Many neurons in both regions have D2 receptors. And interestingly enough, these regions are also linked with schizophrenia. As the research paper notes,
[N]etworks relevant to divergent thinking, i.e. structures and processes in associative corticostriatal-thalamocortical loops overlap to a great extent with regions and networks affected in schizophrenia and bipolar disorder. Furthermore, dopamine is known to influence processing in these networks and alterations in dopaminergic function and activity of D2 receptors have been linked to both positive and negative psychotic symptoms. Two regions appear to be of particular interest in this context: the thalamus and the striatum. Several studies have shown thalamic D2BP to be reduced in drug-naïve schizophrenia patients. Moreover, D2BP in subregions of the thalamus was found to be negatively related to total symptoms, general symptoms, positive symptoms, hostility and suspiciousness as well as grandiosity.

(D2BP refers to D2 "binding potential", which depends on the number density of D2 receptors and their ability to bind dopamine.)

Based on the known facts, the researchers decided to look for correlations between a measure of divergent thinking and D2BP in the thalamus and the striatum. What they found was that, indeed, there was a significant (p=.013) negative correlation, in a relatively small sample of healthy (non-schizophrenic) individuals, between a measure of divergent thinking and D2BP in the thalamus. There was not a similar correlation in the striatum.

In other words, non-schizophrenic people who had lower dopamine activity in the thalamus tended to have higher divergent thinking scores. This is pretty interesting in itself, especially since other studies have shown lower D2BP in the thalamus to be correlated with higher scores for pathological symptoms in schizophrenics.

What, then, is known about the function of the thalamus? It's a left-right midplane symmetric structure, situated between the cerebral cortex and the midbrain. It has a number of functions, especially as a relay station between the cortex and various subcortical areas. In particular, all sensory signals (except smell) pass through substructures of the thalamus on their way to the part of the cortex that processes them. The thalamus is also thought to be important for regulation of sleep, wakefulness, and consciousness – which makes sense, as it's in a position to control what sensory signals get through.

But why do the dopaminergic neurons of the thalamus have something to do with divergent thinking? The present research doesn't explicitly say anything about that. But the researchers suggest some hypotheses:
Based on the current findings, we suggest that a lower D2BP in the thalamus may be one factor that facilitates performance on divergent thinking tasks. The thalamus contains the highest levels of dopamine D2 receptors out of all extrastriatal brain regions. Decreased D2BP in the thalamus has been suggested, firstly, to lower thalamic gating thresholds, resulting in decreased filtering and autoregulation of information flow, and, secondly, to increase excitation of cortical regions through decreased inhibition of prefrontal pyramidal neurons. The decreased prefrontal signal-to-noise ratio may place networks of cortical neurons in a more labile state, allowing them to more easily switch between representations and process multiple stimuli across a wider association range.

Stated more clearly, perhaps, though less precisely, it seems that lower dopamine activity in the thalamus may allow a freer flow of associations to reach the cortex, which is where higher-level cognition takes place. At the same time, however, if this effect is too strong, the result could be cortical activity that is, pathologically, too chaotic.

This post was chosen as an Editor's Selection for
de Manzano, �., Cervenka, S., Karabanov, A., Farde, L., & Ullén, F. (2010). Thinking Outside a Less Intact Box: Thalamic Dopamine D2 Receptor Densities Are Negatively Related to Psychometric Creativity in Healthy Individuals PLoS ONE, 5 (5) DOI: 10.1371/journal.pone.0010670

Further reading:

Creativity linked to mental health (5/18/10)

Link Between Creativity and Mental Illness Revealed (5/19/10)

More brains and bonkers connection: thinking out of a broken box (5/24/10)

Dopamine receptor binding potential in the thalamus and creativity (6/1/10)

Creative madness (8/1/10)

Related articles:

Sugar can be addictive (1/11/09)

Dopamine and obesity (11/17/08)

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