Tag Archives: psychosis

Psychosis and the City

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This post originally appeared on my Psychology Today blog “The Fundamental Four” on 15th Dec. 2011.  This is cross-posted from there.

Abundant evidence exists that psychosis is more prevalent in urban areas as compared to rural areas. The fact that living in the city makes one vulnerable to psychosis is not up for debate – but healthy debate ensues about the mediating mechanisms.
Last year, Zammit et al claimed that the high incidence of psychosis in urban settings is a result of greater social fragmentation in urban areas.
Today I came across a study [pdf] that had nothing to do with psychosis and came up with this novel hypothesis that the mediating mechanism may be global versus local focus or processing style. If that seems farfetched, bear with me for a while.
First a bit of background, the new study was referenced by Christian Jarrett in a BPS research digest blog post in which he lucidly shows that it has been found that living in urban areas has been found to be associated with a propensity for global processing style (seeing the forest); while living in rural areas has been found to be associated with a local processing style (focusing on the trees and missing the forest).

The study itself is pretty straight forward; in one of the local/global task it used the famous Ebbinghaus illusion (see image) to measure the amount of bias towards global vis-a-vis local processing.


In the second task it used large, composite (global) shapes/letters made of small, parts (local) which were also themselves shapes/letters and then measured whether one was more drawn in making inferences/similarity based on global percepts or the local figurine.

The study measured this global vs. local bias in Himba society (Namibia) members who had varying level of exposure to urban environments as well as Japanese and British urbanites. What they found was that living in urban areas/ exposure to urban areas was significantly predictive of whether you would lean more towards more global mode of processing. The authors link this with more ‘visual clutter’ in the cities necessitating a global style of processing.
Christian mentions in passing the fact that autistic people have a very local bias of processing and are marked by weak central coherence; what he perhaps doesn’t realize is that psychotics, which have been conceptualized to lie diametrically opposed on a continuum from autistic, have a global processing bias and a strong central coherence.
Badcock and Crespi, and I even before them, have been crying from the rooftops to conceptualize psychosis and autism as diametrical disorders – and some investigators have paid heed. Suzzana N et al [pdf] have recently shown that as conceptualized by Badcock and Crespi , Autistics and Psychotics are actually at opposed ends of local vs global processing.

To quote:

We refer particularly to Crespi and Badcock (2008), who make the novel claim that the autism and positive schizophrenia spectra are diametrically opposed. They argue that individuals with autistic traits and individuals with positive symptoms of schizophrenia (e.g., magical ideation, unusual perceptual experiences and paranoia) should exhibit opposite cognitive profiles. The current investigation focuses specifically on their claim that autistic and positive schizophrenia traits contrastingly affect preference for local (i.e., piecemeal) versus global (i.e., integrative) processing.

Crespi and Badcock (2008) argue that while autistic traits are associated with a preference for local over global processing, positive schizophrenia traits are associated with a preference for global over local processing. That is, these authors claim that while individuals with autism show a tendency to focus on detail or process features in their isolation, individuals with traits of positive schizophrenia show a tendency to look at the ‘bigger picture’ or process features as an integrated whole. Although a preference for local processing fits theoretically with the tendency of individuals with autism to notice minor features or changes to the environment that are often overlooked by others (Hayes 1987), the link between traits of positive schizophrenia and a preference for global processing is less obvious. It is hypothesized though, that a global processing style could contribute to the complex delusions and enhanced creativity for individuals with positive schizophrenia (Nettle 2006; Oberman and Pascual-Leone 2008), as well as the tendency of these individuals to make ‘‘loose” associations between words and between aspects of the environment (Maher 1983; Spitzer 1997; Spitzer et al. 1993). Importantly, the effect of such loose associations is that one thought does not logically relate to the next, and thus these associations may be strongly linked to the hallucinations and delusions experienced by individuals with positive schizophrenia. However, while there are potential links of local and global processing to features of autism and positive schizotypy, the preferred processing styles for individuals with autistic and schizophrenic traits are yet to be examined together in the one investigation. Therefore, the current study aims to provide the first complete empirical test of Crespi and Badcock’s claim regarding local-global processing.

And this is exactly what they found. They used an embedded figural task to assess the global vs. Local bias and their results showed that indeed psychosis prone individuals had a more global style of processing.

Now one thing I am good at is putting two and two together and the moment I saw the new study correlating global style with urban living, a lot of pieces fell into place. Form the above it is apparent that global processing style may be an intermediate mediating factor that leads to association between urban living and psychosis.

What neural mechanism may be involved?

To quote from the Suzzana et al paper again:

The contrasting preferences for local versus global processing are identified with differences in brain connectivity in particular (Crespi and Badcock 2008). Reference is made to both structural (intrahemispheric and interhemispheric) and functional connectivity. Specifically, Crespi and Badcock argue that the preference for local over global processing displayed by individuals with autistic traits, compared to controls or individuals low on autistic traits, is a result of increased connectivity within neural regions relative to decreased connectivity across regions (Courchesne and Pierce 2005a, b; Happe´ and Frith 2006). Crespi and Badcock then argue that schizophrenia is associated with decreased connectivity within neural regions relative to an increased connectivity across brain regions (Colger and Serafetinides 1990; Siekmeier and Hoffman 2002), leading individuals with traits of positive schizophrenia to favor a global (over local) processing style, compared to controls or people low on these traits. These differences in brain connectivity for autism and positive schizophrenia are said to be mediated, at least in part, by genomic imprinting.

While genomic imprinting may be one mechanism, maybe there is something about exposure to urban environments (maybe it’s ‘visual clutter’) that also has a similar effect on pruning of synapses and unduly affect local pruning at the cost of pruning between widely separated regions thus leading to global processing bias.

Instructive to pause here and note that in children they start with local bias and around 6 year of age revert to global bias that adults typically have and this is mediated by synaptic pruning. See this open access PLOS one article.

Thus, it seems Psychosis and the City are intimately connected; and that, this is because, to live in a city, you need to (de)focus on ‘the big picture’.

 


Caparos, S., Ahmed, L., Bremner, A., de Fockert, J., Linnell, K., & Davidoff, J. (2012). Exposure to an urban environment alters the local bias of a remote culture Cognition, 122 (1), 80-85 DOI: 10.1016/j.cognition.2011.08.013
Crespi, B., & Badcock, C. (2008). Psychosis and autism as diametrical disorders of the social brain Behavioral and Brain Sciences, 31 (03) DOI: 10.1017/S0140525X08004214
Zammit, S., Lewis, G., Rasbash, J., Dalman, C., Gustafsson, J., & Allebeck, P. (2010). INDIVIDUALS, SCHOOLS AND NEIGHBOURHOODS; A MULTILEVEL LONGITUDINAL STUDY OF VARIATION IN INCIDENCE OF PSYCHOTIC DISORDERS Schizophrenia Research, 117 (2-3), 181-182 DOI: 10.1016/j.schres.2010.02.223
Russell-Smith, S., Maybery, M., & Bayliss, D. (2010). Are the Autism and Positive Schizotypy Spectra Diametrically Opposed in Local Versus Global Processing? Journal of Autism and Developmental Disorders, 40 (8), 968-977 DOI: 10.1007/s10803-010-0945-7

 

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Schizophrenia: 4 a’s and ABCD

The term Schizophrenia , as many of the readers will recall, was coined by Eugen Bleuler, a Swiss psychiatrist , who  intended the ‘split personality’ to reflect the fact that there was an underlying dissociation between various functions like memory, cognition, emotion that are normally integrated in normal people.

He also gave the famous 4 a’s that he presumed lied at the core of the schizophrenia and were fundamental aspects of the disorder.

To recall:

‘affect’: Inappropriate or flattened affect-emotions in-congruent to circumstances/situation.

‘autism’: social withdrawal- preferring to live in a fantasy world rather than interact with social world appropriately.

‘ambivalence’ : holding of conflicting attitudes and emotions towards others and self; lack of motivation and depersonalization.

‘associations’ : loosening of thought associations leading to word salad/ flight of ideas/ thought disorder.

Bleuler maintained that these distinctive and fundamental  features identified and formed the core of Schizophrenia while the manifest symptoms like hallucinations and delusions (first rank symptoms as per Schneider) were peripheral and not that important).

The readers of this blog will also be familiar with the ABCD model of psychology where Affect, Behavior (social aspects), Cognition and Desire (motivation/ dynamics)  are the four fundamental domains; it is easy to see how the four a’s of Bleuler map to the 4 domains of psychology and it seems that schizophrenics have major troubles in each domain:

affect: this directly maps to Affect dimension and inappropriate affect is a major core part of the syndrome.

autism: though named somewhat incorrectly the intent of autism was to catch the behavioral and social impediments of the schizophrenics.

ambivalence: here there are conflicts and ambiguities regarding what one desires; for self and for others; lack of motivation/conflicted motivation  is significant at this dimension.

associations: here the cognitive underpinnings are all too evident- the thought disorganization and flight of ideas is all too cognitive in nature.

It is amazing how the insights of Bleuler from a century before lend themselves so easily to fit the ABCD framework. What do you think, a bit stretched? or have I started making loose associations myself 🙂 ?

Mind perception of others: opposing effects of having Autism/Psychosis

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It has been this blog’s thesis that autism and its milder form autism spectrum disorders (ASD) are diametrically opposed to psychosis and its milder form schizotypy.  In no area is this more apparent than in the perception or attribution of minds to others. It thus gave me immense pleasure to read this new article by Wegner et al that looks at how the perception of others’ mind is affected in different sub-clinical conditions like ASD, Schizotypy and Psychopathy.

Wegner et al review a great deal of literature to come to the conclusion that others’ mind perception is a two dimensional construct and that we typically attribute mind to an entity depending on whether the entity can experience like us and whether they have goals and agency like us. Thus people can differ in the perception of either Agency or Experience when they attribute mind to an entity. Also b reviewing the available literature they came to the hypothesis that ASD folks should attribute less of agency , but perhaps equal experience to other humans and other entities as compared to controls; Schizotypals on the other hand have been shown to attribute more of mind and in particular agency to other entities than human. They also hypothesized that owing to lack of empathy the psychoptahs might perceive all animals/humans as lacking experience and thus mind-deficient to an extent and subject to manipulation.

They used online surveys to ascertain scores on ASD, schizotypy and psychopathy and correlated that with mind perception and attribution inclinations.  How they assessed mind perception was by letting the subjects ascribe perceived experience and perceived agency to nine entities viz.  baby, dead woman, dog, God, man , robot, Superman, tree and woman. They performed a confirmatory factor analysis that confirmed that indeed mind perception has two components- Experience and agency.

They got results in line with their hypothesis. ASD folks did  not differ in ascribing Experience to fellow humans but did differ in ascribing agency. Schizotypals on the other hand ascribed too much agency to Robots/animals etc; and in general attributing min dto even things like tress , god and dead woman. Psychopaths on the other hand showed reduced ascription of Experience to other humans as well as animals. As an interesting aside, psychopaths attributed more mind to superman perhaps self-identifying with the fictional character

Thus,  though mind perception in both ASD and Schizotypy is distorted it is tilted one way in autism and the other way in psychosis. With clinical populations the authors hope to get even stronger results. I am pleased because finally people have started taking the autism is opposed to psychosis paradigm seriously and have started doing research around it that is leading to fruitful results and confirmations.

Another new study that I came across recently and would like to link to found that VPA (valproic acid) treated mice were indeed an apt model of autism in mice and had the same brain correlates and signatures as in Autistic people. It is worth noting that VPA/sodium valproate is used to treat psychosis and I have pointed earlier too how this indicates that autism and psychosis are di\ametrically opposed. It is good that we are getting multiple confirmations of the important autism-psychosis opposition theory.

Gray, K., Jenkins, A., Heberlein, A., & Wegner, D. (2010). Distortions of mind perception in psychopathology Proceedings of the National Academy of Sciences, 108 (2), 477-479 DOI: 10.1073/pnas.1015493108

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Autism and white Matter/Myelination: the opposite of creativty/psychosis phenotype?

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A new paper by Ben Bashat et al extends their earlier findings that had found that there was accelerated maturation of white matter in children with Autism. In this new paper they use Tract Based Spatial statistics (TBSS) to determine the white matter integrity of children (age around 3 years) with Autism as compared to normal controls. Of course they used Diffusion tensor Imaging to find out Fractional anisotropy and other measures of white matter integrity.

Essentially they found that in some regions/tracts there was greater Fractional Anisotropy (FA) as compared to controls. These regions/tracts were genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). They also found that in areas of high FA there was corresponding decrease in Radial diffusivity (Dr). What this essentially means, to my naive mind, is that greater conductance or speed of action potential in axons would primarily be due to enhanced myelination which reduces leakage or lateral flow of AP.

I’ll like to contrast the results with an earlier study I had blogged about regarding creativity, psychopathology and white matter mylienation connection. As per that study an inverse relation was found between people high on creativity (divergent type) and Fractional anisotropy in frontal regions, i’e there was low FA. Also importantly there was increased Dr (radial diffusivity) in the same regions and thus the conclusion was that there was reduced myelination in those areas which meant reduced signal transmission speed and more signal leak . It is notable that that study too used DTI and Tract based Spatial statistics (TBSS) analysis method to arrive at their conclusions.

Regular readers of this blog will know my fanaticism for Autism and Psychosis as opposites on a continuum theory. This new paper nicely fits in with my last post linking creativity/psychosis and white matter/myelination, I had as much surmised that Autism would show the opposite effect and have high FA and decreased Dr. It is heartening to note when such a relation is found and reported- goes to show the strength and ability to make predictions of the theory.

However, I would also like to point out and highlight that I believe Autistic spectrum is characterized by another type of ability – the savantic intelligence– that may be directly due to this white matter /excess myelination effect. Perhaps the signals travel so fast that decisions are made locally without the time available to get other far-0off regions involved- thus giving attention to details but inability to link disparate regions and ideas.

Weinstein, M., Ben-Sira, L., Levy, Y., Zachor, D., Itzhak, E., Artzi, M., Tarrasch, R., Eksteine, P., Hendler, T., & Bashat, D. (2010). Abnormal white matter integrity in young children with autism Human Brain Mapping DOI: 10.1002/hbm.21042
Ben Bashat, D., Kronfeld-Duenias, V., Zachor, D., Ekstein, P., Hendler, T., Tarrasch, R., Even, A., Levy, Y., & Ben Sira, L. (2007). Accelerated maturation of white matter in young children with autism: A high b value DWI study NeuroImage, 37 (1), 40-47 DOI: 10.1016/j.neuroimage.2007.04.060
Jung, R., Grazioplene, R., Caprihan, A., Chavez, R., & Haier, R. (2010). White Matter Integrity, Creativity, and Psychopathology: Disentangling Constructs with Diffusion Tensor Imaging PLoS ONE, 5 (3) DOI: 10.1371/journal.pone.0009818

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More brains and bonkers connection: thinking out of a broken box

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We have covered many studies linking creativity with Psychosis and this new study by Manzano et al provides further corroborating evidence.

Dopamine has been linked with psychosis and is now also being increasingly being linked with creativity, especially divergent creativity and thinking style.

Divergent thinking is influenced by dopaminergic function. Reuter [6] found a correlation between divergent thinking (the Inventiveness battery of the Berliner Intelligenz Struktur Test) and polymorphisms of the dopamine D2 receptor gene–DRD2 TAQ IA. Higher creativity scores were observed in carriers of the A1 allele. This polymorphism is unrelated to general intelligence [7], [8], which suggests that it is more specifically related to Glr (“long-term storage and retrieval”). This finding is in line with functional imaging research showing the D2 system to be involved in attentional set shifting and response flexibility, which are important components of divergent thinking [9]. Furthermore, the finding indicates that divergent thinking is related to regional differences in D2 densities, since the DRD2 TAQ IA polymorphism has been shown to modulate D2 binding potential (D2BP) in both striatal [10] and extrastriatal regions [11].

Divergent thinking is traditionally measured using alternate uses test, for eg., in which a familiar object like brick is provided and subjects asked to name novel use for that object. The responses are marked for creativity as per the follwoing criterion:

  • 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)

The main findings of the study was that dopamine D2 binding potential (D2BP) receptor density in thalamus correlated negatively with divergent thinking and creativity scores. Here is how the authors interpret the results:

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 [33], [45]. Decreased D2BP in the thalamus has been suggested, firstly, to lower thalamic gating thresholds, resulting in decreased filtering and autoregulation of information flow [31] and, secondly, to increase excitation of cortical regions through decreased inhibition of prefrontal pyramidal neurons [46], [47], [48]. 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 [49]. This state, which we hereforth will refer to as the “creative bias”, could benefit performance on tasks that involve continuous generation and (re-)combination of mental representations and switching between mind-sets. The creative bias could also explain why the different measures of divergent task performance correlate: A decreased signal-to-noise ratio in thalamus would decrease information gating and possibly increase fluency; decreased signal-to-noise ratio in cortical regions should better enable flexibility and switching between representations; similarly, the associative range should be widened and selectivity should be decreased which might spur originality and elaboration.

Besides carrying benefits related to fluency and switching, the decreased signal-to-noise ratio associated with the creative bias should be disadvantageous in relation to tasks that require high levels of selective attention. Some support for this prediction can be taken from Dorfman [50] who showed that the greater a person’s divergent thinking scores, the slower his or her reaction times were on a negative priming task requiring the inhibition of interfering information. Furthermore, the creative bias may also bring a risk of excessive excitatory signals from the thalamus overwhelming cortical neurotransmission, with ensuing cognitive disorganization and positive symptoms [30]. It is thus tempting to suggest that dopaminergic modulation of neurotransmission mediated through dopamine D2-receptors could be one of the mechanisms which associate creativity with positive psychotic symptoms. Interestingly, positive symptoms are not necessarily related to problems in executive function, at least not to the same extent as negative symptoms [51], which indicates that in the creative individual “blind variation” might be affected without a concomitant decline in “selective retention”. It can be speculated that aberrant thalamic function may promote unusual associations, as well as improved performance on divergent thinking tests in healthy individuals, in the absence of the detrimental effects typically associated with psychiatric disorders. In other words, thinking outside the box might be facilitated by having a somewhat less intact box.

In plain English speak, the same decreased signal-to-noise ratio in perfrontal regions that gives rise to creativity also gives rise to proneness to psychosis. The more the noise that is introduced the greater the chances that the ideas generated by ‘blind variation’ are more creative; if the ‘selective retention’ procedure is also defective or loosened to an extent, it may result in psychopathology and psychosis, while if intact it leads to creativity. Thus while one factor , that of loosening of associations, flexibility and set switching is common to both psychosis and creativity, the defects in selective retention may be the crucial factor that distinguishes brains from bonkers.

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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

The Creativity-dopamine (b)linkage: more brains and bonkers connections

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rh?zom?ng Cam?ra?Obscura pl?ats . .
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Creativity is certainly different from intelligence; it is usually gauged as the ability to make novel and useful unique contributions to a field. Creativity itself is not a unified construct but can be broken into convergent creativity (involving more focused approach) and divergent creativity (involving more widening and loosening of associations).

It has been evident for quite some time that there is a connection between insanity (especially bipolar/schizophrenia spectrum) and creativity , especially as evidenced by the creative bent of schizotypal people. See for example this article covering a recent study that looks at exactly the same issue. However, most of these studies rely on a unitary construct of creativity that does not do full justice to the correlations that could be found if convergent and divergent creativity was distinguished and effect of intelligence was factored out. The new study by Hommel, B. does just that.

Schizophrenia/psychosis as many will know from their elementary neuroscience knowledge is associated with dopamine dysfunction; specifically it is believed that high baseline dopamine levels are there in schizophrenics/psychotics. So it was not unreasonable for Hommel et al to hypothesize that dopamine should have some relation with creativity possible higher dopamine associated with high creativity. However, dopamine has shown an inverse U relation for many other factors and thus they were cautious and tried to fit both linear and quadratic graphs to their data. But we are moving ahead of ourselves. Before they could find the underlying relation between dopamine and creativity, they had to measure these things accurately.

They measured dopamine using Eye Blink Rate (EBR): that is how many time you blink in a minute. For creativity , they measured Convergent Creativity using a remote association task (don’t go by the name …the task has only one answer and measures convergent thinking) . for eg. a subject is given three words (say time, hair, stretch) and have to come up with a word that is commonly related to all three (answer: long) . this reliably measures creativity but of he convergent type. For Divergent thinking , they administered the Alternate Uses task (AUT),a task that requires one tocome up with novel uses of everyday objects like brick, toothpaste etc. The responses to AUT were further coded for fluency (how easily one could come up with alternatives measured by total no. of responses) , flexibility(the number of different categories used or how remote the mind wandered) and elaboration (the level of detail surrounding the use). They also measured fluid intelligence using Raven’s progressive matrices.

They then conducted experiments (administered the tests to subjects) , collected data and analyzed the results. The main findings of interest to us is that they found a inverse u shaped relation between dopamine (EBR) and flexibility dimension fo divergent thinking. This effect was present even when the effect of intelligence was factored out. thus both low dopamine, as well as too much dopamine is detrimental to flexible divergent thinking/creativity and schizotypals , placed precariously between normals and psychotics are best placed to be the most creative as they presumably have the optimum dopamine levels. the authors also argue that schizophrenics dopamine levels should not be brought down indiscreetly by using anti-psychotics (which reduce dopamine levels) but they should be brought in the optimum range of dopamine functioning. this obviously has immense importance and treatment implications. No wonder creative people feel stiffed when on anti-psychotics- their dopamine levels are being brought down way too much.

The other interesting finding was that dopamine (EBR) was negatively ad linearly related to convergent thinking. Thus, it is evident that convergent creativity and divergent creativity are different constructs and while dopamine has a complex quadratic relationship with divergent thinking, that with convergent thinking is linear though not very comforting. It seems that as dopamine levels increase the ability to narrow focus diminishes and this would be concordant with other studies linking dopamine to ADHD for example.

Overall, a view of how brains and bonkers are two sides of the same coin is emerging and it is exciting to note that many previous inconsistencies in literature around this issue may have to do with not differentiating and decomposing creativity into its many components and not looking for inverse u shaped effects.

Chermahini SA, & Hommel B (2010). The (b)link between creativity and dopamine: Spontaneous eye blink rates predict and dissociate divergent and convergent thinking. Cognition PMID: 20334856

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Creativity-psychosis linkage via reduced white matter /myelination

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I have been following, and am passionate about, the positive psychology movement for quite some time, but was surprised to discover that there was something called positive neuroscience also in place. I recently came across this new scientist article about the research paper of Rex Jung et al and was pleased to discover that Jung was working on the frontier of applying latest in neuroscience research to Positive brain states and substrates like that involved in creativity.

The article is in PLOSOne, an open access journal and is lucidly written , so you should go and read it now. I’ll anyway like to summarize their study results. First a bit of background about creativity psychopathology linkage.

Some research reports positive correlations between various definitions of creativity and a diagnosis of psychopathology [1], [2], [3], [4]. Other studies report that psychopathology is rarely, if ever, associated with creative insight, capacity, or productivity [5]. When artists are studied more carefully, certain personality characteristics appear to reside upon a continuum of both normal behavior and psychopathology. For example, creative expression in the visual arts and poetry has been linked with the overlapping personality traits of schizotypy and Openness to Experience (Openness), and particularly to self-reports of “unusual experiences” and “unconventional nonconformity”, but not the “introvertive anhedonia” characteristic of schizophrenia [6].

This is inline with what we have been covering at mouse trap regarding association of creativity with the psychotic spectrum especially the creativity that is artistic or revolutionary in nature rather than scientific and methodical in nature. This is how the authors distinguish between types of creativity inline with my views that one type of creativity is autistic (cognitive) in nature while the other is psychotic (emotional) and these are on a continuum.

First, there does not exist one “creativity”; rather, this construct is hypothesized to reside upon a continuum between cognitive (i.e., scientific) and emotional (i.e., artistic) behavioral domains [41], [42]. Thus, when comparing scientists and artists directly, researchers have found lower lifetime rates of psychopathology for: 1) scientists compared to artists, 2) natural scientists compared to social scientists, 3) nonfiction writers compared to fiction writers and poets, and 4) formal artists compared to “expressive” artists [3], [4], [43]. These findings have led researchers to hypothesize a hierarchical structure of creativity across disciplines [42], which echoes the notions of “paradigmatic” (i.e., a fundamental model of events) versus “revolutionary” (i.e., rejection of doctrines) approaches as applied to the sciences [44]. The benefits of working within the lines of a given field appear to be lower levels of psychopathology; alternately, individuals with lower levels of psychopathology may be attracted to such endeavors. Similarly, there is increasing evidence that the cost of “revolutionary” approaches to creative endeavors, whether it is in the arts or sciences, may be associated with increased levels of psychopathology although, again, causative links are weak at best.

So that fits in with broader creativity/ psychopathology linkage, but to get back to the current study the authors had already established earlier that performance on Divergent Thinking (DT) (a measure of creativity) “exhibited significant inverse relationships with both cortical thickness in frontal lobe regions and metabolite concentration of N-acetyl-aspartate (NAA) in the anterior cingulate cortex in normal young subjects “. Thus, some theoretical relationship between creativity and underlying brain circuitry in the frontal reagion was available a priori. Also, research by other researchers has already established that ” Both schizophrenic and bipolar patients have been shown to have reduced fractional anisotropy (FA) in the anterior thalamic radiation [12], [13] and uncinate fasciculus [14] within frontal brain regions. Similarly, reduced FA was observed within the uncinate fasciculus of a cohort with schizotypal personality disorder, providing strong support for the hypothesis that similar neural phenotypes may not result in full-blown clinical symptoms [15]. Finally, in normal subjects, the Neuroregulin-1 (NRG1) single nucleotide polymorphisms (SNP’s) SNP8NRG243177 and SNP8NRG221533 were found to predict lower FA in the left anterior thalamic radiation [16]. As NRG1 has been found to predict higher risk of schizophrenia [17], [18] and bipolar disorder [19], and is linked with axonal myelination and migration [20], these authors hypothesize a mechanistic link between NRG1 within the anterior thalamic radiation and risk for psychotic disorders [16].”

Thus, from the above it is easy to see that there should be a inverse relationship between Fractional Anisotropy (a construct related to myelination of axons) in the frontal regions and creativity if one assumes that creativity and psychopathology are related and are on one end of a continuum. And this inverse relationship between creativity and FA is exactly what they found:

Our results suggest a convergence between a cognitive measure of divergent thinking, a personality measure of Openness, and a white matter integrity measure within the inferior frontal lobes. We found that normal young subjects with lower levels of FA within predominantly left inferior frontal white matter (i.e., regions overlapping the uncinate fasciculus and anterior thalamic radiation) scored higher on the CCI; similarly subjects with lower levels of FA within the right frontal white matter (i.e., regions overlapping the uncinate fasciculus and anterior thalamic radiation) scored higher on self-reported measures of Openness. These two regions of white matter overlap with those reported by other researchers who found lower FA in both schizophrenia and bipolar disorder [13], [14], [30].

They could also nail the reduced FA to reduced myelination as radial diffusion was affected more than axial diffusion. As reduced myelination has been shown as a diatheisis for psychosis, this fits in with previous research linking risk factors common to psychosis and creativity.

Whereas more neural resources are often associated with higher intellectual capacity in a parieto-frontal network of brain regions [39], studies in DT appear to suggest that less is often better in a different network of brain regions, particularly fronto-cingulate-subcortical networks linked via white matter loops [40].

One can speculate that frontal region, more concerned with executive control , when with reduced activity or functional connectivity , may not inhibit the other brain regions that much, and may thus lead to flowering of inherent creativity and cross-talk amongst different brain regions. On the other hand too much white matter/ gray matter in this region may lead to too much control and leave little room for flexibility and creativity.

However, while lower FA is commonly seen in diseases where both cognition and white matter integrity are impaired (e.g., Traumatic Brain Injury, Schizophrenia, Alzheimer’s disease) [45], [46], [47], evidence is accumulating that higher FA in particular brain regions may also be associated with clinical disorders including post-traumatic stress disorder [48], obsessive-compulsive disorder [49], panic disorder [50], synaesthesia [51], and Williams syndrome [52].

It is interesting to note that enhanced FA is associated with clinical disorder of Williams syndrome, which is associated with Autism; on the other end of continuum, reduced FA in particular brain region is associated with psychosis proneness, thus providing another convergent linkage of autism and psychosis as opposites.

Jung, R., Grazioplene, R., Caprihan, A., Chavez, R., & Haier, R. (2010). White Matter Integrity, Creativity, and Psychopathology: Disentangling Constructs with Diffusion Tensor Imaging PLoS ONE, 5 (3) DOI: 10.1371/journal.pone.0009818

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Am happy, will seek novelty; am sad, will stick with familiar

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I have earlier written about the entrepreneurial roller-coaster and how when entrepreneurs are in a happy mood, they focus on long-term vision related creativity; while when they are in negative mood they focus on the task at hand. I had also tried to relate this to prevention and promotion focus and weave it in the narrative of preventive focus as depressive and promotion focus as being manic in nature.

Another bit of research extends the thesis and adds to our knowledge base. This new article by Winkielman et al suggest that people in sad mood tend to value familiarity whereas those in a happy mood are more open and welcoming of novelty.

Here is the abstract of the study:

People often prefer familiar stimuli, presumably because familiarity signals safety. This preference can occur with merely repeated old stimuli, but it is most robust with new but highly familiar rototypes of a known category (beauty-in-averageness effect). However, is familiarity always warm? Tuning accounts of mood hold that positive mood signals a safe environment, whereas negative mood signals an unsafe environment. Thus, the value of familiarity should depend on mood. We show that compared with a sad mood, a happy mood eliminates the preference for familiar stimuli, as shown in measures of self-reported liking and physiological measures of affect (electromyographic indicator of spontaneous smiling). The basic effect of exposure on preference and its modulation by mood were most robust for prototypes (category averages). All this occurs even though prototypes might be more familiar in a happy mood. We conclude that mood changes the hedonic implications of familiarity cues.

The authors reasoning is as follows:

Happy or sad mood signal the safety of the environment.

Much psychological research points out that one signal of environmental safety or danger is an individual’s mood (e.g., Clore, Schwarz, & Conway, 1994; Schwarz, 2002). Bad mood signals a problem, tuning individuals toward safety concerns, whereas good mood signals that an environment is benign. Tuning accounts assume that mood adjusts cognitive and affective reactions so that they best serve the individual in the specific context.

In a safe environment, one can experiment or value novelty. In an unsafe environmental it makes sense to stick to tried and proven things.

After all, familiarity is only a heuristic cue to safety. Thus, as with any heuristic cue, its validity and hedonic meaning vary by context (Hertwig, Herzog, Schooler, & Reimer, 2008). Specifically, the familiarity-positivity link should depend on whether individuals are tuned toward safety concerns. Familiarity should be valued in an unsafe environment, but less so in a benign environment (e.g., Bornstein, 1989). Analogously, in a strange city a familiar face elicits a warm glow, whereas locally the same face prompts a yawn. Numerous studies (and parents) have observed that in unsafe environments infants are neophobic, but in safe settings, they are less so (Shore, 1994). Similarly, in multiple species, stress increases neophobia, whereas comfort reduces it.

Thus they hypothesize that sad mood should lead to mare liking for familiarity while happy mood should lead to novelty preference. They do some clever experimentation and get exactly the same result.

To me this is extension of promotion focus is expansive, is happy, is creative and long-term, and is novelty preferring versus prevention focus is restrictive, is sad, is focused on the task at hand, and is familiarity preferring. In other words people in safe environments having promotion focus are manic while those in unsafe environments and having prevention focus are depressive.

Another finding that struck out from the current paper was that the (false) memory for prototype was increased in positive mood condition. This is congruent with the fact that the promotion focus / mania condition has a more narrative focus that tries to weave a narrative around things and remembers a gist rather than is accuracy based and tries to recall the exact events. thus, I believe the risk of delusions and hallucinations magnifies as one goes deep into promotion focus / mania and starts weaving narratives and having false prototypical memories of events/happenings.

de Vries, M., Holland, R., Chenier, T., Starr, M., & Winkielman, P. (2010). Happiness Cools the Warm Glow of Familiarity: Psychophysiological Evidence That Mood Modulates the Familiarity-Affect Link Psychological Science DOI: 10.1177/0956797609359878

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Autism and Schizophrenia: proof from comparative genomics

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I have blogged extensively about the Autism and Schizophrenia as opposites on a continuum theory. I remember first putting this theory in words in an article 3 yrs back on the mouse trap titled Autism and Schizophrenia: the two cultures. That 2006 article, in turn, was inspired by Daniel Nettle’s 2005 article in Journal of Research in Personality where Nettle had also proposed the dichotomy and that paper helped crystallize my thoughts on the subject, a theory which I had been building on my own and now supported by someone like Nettle who I respect a lot. Important to note that at that time I was blissfully unaware of Badcock or Crespi and their work. It is to the credit of Badcock that he had published in 2006 his own theory of Autism and Schizophrenia as opposites on a continuum based on parental imprinting of genes and proposed a mechanism. Crespi I guess got involved in Badcocks’s efforts later on and gave it more experimental and theoretic grounding. I firts became aware of Badcock and Crespi’s work in early 2008.

The wider world became aware of the Autism/Schizophrenia dichotomy sometime in late 2008 (November 2008) . at that time too, I was a little disappointed because most of the coverage did not mention Daniel Nettle, who I think should be credited for this work and line of reasoning too. As a consolation, some reports did mention Chris Frith who has also been partly supporting the thesis.

I wanted to give a historical perspective, because I am sure the recent Crespi article would be grabbed on by mainstream media and the pioneers Chris Frith/Nettle perhaps overlooked- but to me they too are heroes for having come up with such profound early insights. this is not to discredit teh work of Badcock and Crespi- they are doing a thorough job of convincing the skeptics and delineating the exact mechanism and genetics involved.

While we are on the topic of historical perspective , let me also pat myself on the back. In May 2008, a study came out that de novo Copy Number Variations’s (CNVs) were quite high in schizophrenics and they are in the same region as that for autistics who also have high CNVs in the same region. While some took that result to imply that Schizophrenia and Autism are same and are not different, I persisted and proposed a mechanism, whereby they could still be opposites : To quote:

Now as it happens previous research has also found that CNVs are also found to a higher extent in autistics. Moreover, research has indicated that the same chromosomal regions have CNVs in both Autism and Schizophrenia. To me this is exciting news. Probably the chromosomal region (neurexin related is one such region) commonly involved in both schizophrenia and autism is related to cognitive style, creativity and social thinking. Qualitatively (deletions as opposed to duplications) and quantitatively (more duplications) different type of CNVs may lead to differential eruption of either Schizophrenia or Autism as the same underlying neural circuit gets affected due to CNVs, though in a different qualitative and quantitative way.

Now one and half year later Crespi et al report the results of their study which has found exactly the same- that is, if deletions in some locus lead to autism, duplications lead to schizophrenia and vice versa. That to me is clinching evidence of my thesis. Who says Science does not happen on blogs- I proposed something to flow as a consequence of theory and exactly the same thing is found as per the hypothesis. I feel vindicated and emotional to some extent. Loves labor has not been lost to deaf ears.

Let us then return to the new and latest study that has sort of proven that Autism and Schizophrenia are opposites, genetically. Crespi et al, report in the latest PNAS edition that comparative genomics leads to that conclusion. What Crespi et al did was look at theCNV s and the locus whee CNV in both Autism and Schizophrenia are involved and sure enough they found the pattern I had proposed. I’ll now quote from the abstract and the article extensively:

We used data from studies of copy-number variants (CNVs), singlegene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (i) autism subsumed in schizophrenia, (ii) independence, (iii) diametric, and (iv) partialoverlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance. However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia. Evidence from the effects of risk variants on growth-signaling pathways shows that autism-spectrum conditions tend to be associated with upregulation of pathways due to loss of function mutations in negative regulators, whereas schizophrenia is associated with reduced pathway activation. Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth.These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain.

Copy Number Data. Rare copy-number variants (CNVs) at seven loci, 1q21.1, 15q13.3, 16p11.2, 16p13.1, 17p12, 22q11.21, and 22q13.3 (Tables S1 and S2), have been independently ascertained and associated with autism and schizophrenia in a sufficient number of microarray-based comparative genomic hybridization (aCGH) and SNP-based studies to allow statistical analysis of the frequencies of deletions versus duplications in these two conditions (Table 1, Tables S3–S9). For five of the loci (1q21.1, 16p11.2, 16p13.1, 22q11.21, and 22q13.3), specific risk variants have been statistically supported for both autism and schizophrenia using case-control comparisons, which allows direct evaluation of the alternative hypotheses in Fig. 1. One locus (16p13.1) supports a model of overlap, and four loci support the reciprocal model, such that deletions are associated with increased risk of autism and duplications with increased risk of schizophrenia (16p11.2, 22q13.3), or deletions are associated with increased risk of schizophrenia and duplications with increased risk of autism (1q21.1, 22q11.21). For 1q21.1 and 22q11.21, contingency table analyses also indicate highly significant differences in the frequencies of deletions compared with duplications for the two disorders, such that schizophrenia is differentially associated with deletions and autism with duplications. By contrast, for 16p11.2 and 22q13.3 such analyses show that autism is differentially associated with deletions and schizophrenia with duplications.

Model_1

I cannot cut n paste the table, but a look at the table clears all doubts. They also look at gene association data and come to a similar conclusion ruling out model A (autism, subsumed in schizophrenia) or model B (autism and schizophrenia are independent of each other).

Models 1C (diametric) and 1D (overlapping) both predict broad overlap in risk genes between autism and schizophrenia, and do not necessarily predict an absence or paucity of genes affecting one condition but not the other. In theory, these models can be differentiated by using data on specific risk alleles for specific loci (such as single-nucleotide polymorphisms, haplotypes, or genotypes), which should be partially shared under the overlapping model but different under the diametric model. For the genes DAO, DISC1, GRIK2, GSTM1, and MTHFR, the same allele, genotype, or haplotype was associated with both autism and schizophrenia, and for the genes AHI1, APOE, DRD1, FOXP2, HLA-DRB1, and SHANK3, alternative alleles, genotypes, or haplotypes at the same loci appear to mediate risk of these two conditions (SI Text). For the other genes that have been associated with both conditions, heterogeneity in the genetic markers used, heterogeneity among results from multiple studies of the same genes, and the general lack of functional information preclude interpretation in terms of shared or alternative risk factors.

Models of autism as a subset of schizophrenia (Fig. 1A), and autism and schizophrenia as independent or separate (model 1B), can be rejected with some degree of confidence, but models involving diametric etiology (model 1C) or partial overlap (model 1D) cannot be clearly rejected. Taken together, most of the data and analyses described here appear to support the hypothesis of autism and schizophrenia as diametric conditions, based primarily on the findings that reciprocal variants at 1q21.1, 16p11.2, 22q11.21, and 22q13.3 represent statistically-supported, highly-penetrant risk factors for the two conditions (Table 1), and that for a number of genes, alternative alleles or haplotypes appear to mediate risk of autism versus schizophrenia.
Additional lines of evidence supporting the diametric hypothesis, from previous studies of autism and schizophrenia, include:

  • 1. Data showing notable rarity of familial coaggregation of autism with schizophrenia (38), in contrast, for example, to strong patterns of co-occurance within pedigrees of schizophrenia, schizoaffective disorder, and bipolar disorder (39).
  • 2. Psychiatric contrasts of Smith-Magenis syndrome with Potocki-Lupski syndrome (due to the reciprocal duplication at the Smith-Magenis locus), Williams syndrome with cases of Williams-syndrome region duplication, and Klinefelter syndrome with Turner syndrome, each of which tends to involve psychotic-affective spectrum phenotypes in the former syndrome, and autistic spectrum conditions in the latter (5, 40).
  • 3. Effects of autism and schizophrenia risk alleles on common growth-signaling pathways, such that autism has been associated with loss of function in genes, such as FMR1, NF1, PTEN, TSC1, and TSC2 that act as negative regulators of the PI3K, Akt, mTOR, or other growth-signaling pathways (41–45), whereas schizophrenia tends to be associated with reduced function or activity of genes that up-regulate the PI3K, Akt, and other growth-related pathways (46–49).
  • 4. Increased average head size, childhood brain volume, or cortical thickness in individuals with: (i) idiopathic autism (50–53), (ii) the autism-associated duplications at 1q21.1 (17) and 16p13.1 (32) and the autism-associated deletions at 6p11.2 (31), and (iii) autism due to loss of function (or haploinsufficiency) of FMR1 (54), NF1 (55), PTEN (56) and RNF135 (57). By contrast, reduced average values for brain size and cortical thickness, due to some combination of reduced growth and accelerated gray matter loss, have been demonstrated with notable consistency across studies of schizophrenia (58–62), and such reduced head or brain size has also been associated with the schizophrenia-linked CNVs at 1q21.1 and 22q11.21 (17, 63, 64), and with deletions of 16p13.1 (65).

I am more than pleased with these results. Badcock too is. You can read his comments here. What about you? What would it take to convince you? 🙂

Crespi, B., Stead, P., & Elliot, M. (2009). Evolution in Health and Medicine Sackler Colloquium: Comparative genomics of autism and schizophrenia Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0906080106

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Logos Vs Mythos: Autism Vs Schizophrenia

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I recently came across this TED talk by Devdatt Patnaik, A chief Belief Officer in an Indian industry group and was fascinated by his description of the distinction between logos based ‘the’ world which is objective, logical, universal, factual and science based and mythos based ‘my’ world which is subjective,emotional, personal, belief-based and mythological in nature. while ‘the’ world tries to answer ‘how’, ‘my’ world tires to answer ‘why’.

To me the same is true of Autism and Psychosis dichotomy. While autistic frame of reference is rooted in ‘the’ world – trying to apply a science based approach even to the mind and mental; the psychotic frame of reference becomes detached from ‘the’ world and is totally enamored by the subjective depths of ‘my’ world -attributing mental properties to physical things too.

Devdatt, later on goes to contrast East Vs West Myths and here at the second order , though we are talking of mythos and not of logos and are in the psychotic/mythic world , we see a difference in focus, between the eastern traditions and the western traditions. While the east is portrayed as more spiritual and renunciation-believing in multiple lives and thus multiple chances; the west is depicted as more materialistic and ambitious and believing in one and only life and thus believing in only one chance of redemption -and though this dichotomy may be simplistic it does bring into focus the fact that the cultures do differ profoundly.

The difference between cultures and mythologies, and the people shaped from them thereof, is important in light of a new study , for eg., that demonstrates that most of the behavioral research is carried on with WEIRD people! WEIRD stands for Western, Educated, Industrial, Rich and Democratic subjects and the paper claims that these WEIRD subjects are outliers and not representative of the general population. If much of the scientific and psychological research is done on WEIRD subjects (which is a fact) and if WEIRD are not representative of the population (which seems reasonable given the differences in culture and the ability of culture to shape people) , than that raises a more serious questions on the results of behavioral studies than the voodoo correlations paper raised questions about the fMRI studies.

Devdutt, though seems to be slightly biased towards Indian culture, but the TED talk is worth a watch. And you may also find one of my earlier post relating Indian culture,religion, and Autism, Schizophrenia quite pertinent here.

Do you think Devdutt is right when he stresses differences in cultures and myths? If so, do you think Culture shapes people? and if so do you believe with Norenzayan et al that if we just do studies based on WEIRD subjects, our results are not representative but skewed. Lot of questions to think about!

Joseph Henrich, Steven J. Heine, & Ara Norenzayan (2009). The Weirdest People in the World? Behavioral and Brain Sciences

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