Posts tagged schizophrenia

ebbinghaus

Psychosis and the City

English: Himba village about 15 km north of Op...

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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 :-) ?

ADHD and CNVs

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I have written previously about CNV’s and how de novo CNV’s have been recently shown to correlate with disorders like autism and schizophrenia. I have also been militantly proposing that autism and psychosis are diametrically opposed disorders and have been gladdened to find that recent CNV data support that hypothesis.  I reported how 16p11.2 duplications were associated with schizophrenia while micro-deletions at same site associated with autism.  I also reported how a larger study which looked at multiple CNVs found the same reciprocal effects on CNV sites for autism and schizophrenia, thus bolstering the hypothesis that these are diametrically opposed.

By now you might be wondering what all this has to do with ADHD? Well, for one, early this year I started expanding my model and started conceptualizing ADHD as opposed to Autism in childhood and ADHD thus as belonging to psychotic spectrum; I mused that perhaps the same genetic vulnerability that leads to ADHD in childhood could lead to the manifestation of psychosis in teenage/adulthood. Its worthwhile noting that both ADHD and Psychosis are highly correlated with creativity.

So I could not stop my exuberance at finding that CNVs at another site 16p13.11 has been implicated in ADHD and the duplications are present in both ADHD and Schizophrenia. Also, as per the same study , ADHD children carry a large number of de novo CNV’s – a pattern similar ro Autism/schizophrenia. Some, for example the Neuroskeptic, have taken the same loci of CNVs to mean that these CNVs just confer a general risk of maladaptation, but I think they are missing the forest for the trees.  The pattern points to the diametrical model and how CNvs are one mechanism in which tug-of-wars are played (whether evolutionary variation or parent-offspring or between paternal and maternal genomes).

Let me explain what I mean by tug-of-wars. Say you have a evolutionary trade-off between exploration and exploitation, with one extreme being useful in some extreme environmental niche (say food is abundant)  and the other strategy useful in the opposed environmental niche  (say food is scare) . The trait that gets stabilized  should have a bell cure distribution so that the a species can survive even if environment leans toward one extreme.  The way to archive this could be by having distribution of frequency of different alleles; or it can be via CNV mechanism.  You may have some gentic loci for exploration and have a  single popular gene allele that codes for exploration at that loci and CNVs that cause deletions here will lead to more exploitation while CNVs that are duplications will lead to more exploration.  Thus, by CNV mechanism one can have more of good thing or less of a good thing, good depending on context (i.e context says what is ‘good’).

To take the example of  16p13.11 – it seems it is somehow related to mental retardation/ creativity/intelligence. A deletion at this site causes mental retardation/multiple congenital anomalies.=, while duplications have benign effects. I would conjecture that duplications (associated with ADHD and schizophrenia) may actually increase intelligence/ creativity.   That woudl fit with the diametrical model and the finding that ADHD  kids are more creative nd develop language more readily than autistic kids of same age.

I am pasting the background and findings from the abstract below:

Large, rare chromosomal deletions and duplications known as copy number variants (CNVs) have been implicated in neurodevelopmental disorders similar to attention-deficit hyperactivity disorder (ADHD). We aimed to establish whether burden of CNVs was increased in ADHD, and to investigate whether identified CNVs were enriched for loci previously identified in autism and schizophrenia.
Data for full analyses were available for 366 children with ADHD and 1047 controls. 57 large, rare CNVs were identified in children with ADHD and 78 in controls, showing a significantly increased rate of CNVs in ADHD (0·156 vs 0·075; p=8·9×10?5). This increased rate of CNVs was particularly high in those with intellectual disability (0·424; p=2·0×10?6), although there was also a significant excess in cases with no such disability (0·125, p=0·0077). An excess of chromosome 16p13.11 duplications was noted in the ADHD group (p=0·0008 after correction for multiple testing), a finding that was replicated in the Icelandic sample (p=0·031). CNVs identified in our ADHD cohort were significantly enriched for loci previously reported in both autism (p=0·0095) and schizophrenia (p=0·010).

To some the fact that ADHD had the same loci as both Autism and Schizophrenia may speak against there being a diametrical relation; however the same was claimed when initially it was found that autism and schizophrenia CNVs were at the same loci; only after looking at the nature of CNV’s (whether duplications or deletions) were the researchers able to identify the diametrical nature of the CNV’s

I haven’t read the full paper yet (waiting for someone to send me the paper) and as and when I get my hands on the full paper, I’ll update this blog post with more details.

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Williams, N., Zaharieva, I., Martin, A., Langley, K., Mantripragada, K., Fossdal, R., Stefansson, H., Stefansson, K., Magnusson, P., & Gudmundsson, O. (2010). Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis The Lancet DOI: 10.1016/S0140-6736(10)61109-9

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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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Dopamine and theory of mind: another autism/schizophrenia dichotomy

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There is an article in press in Neuropsyhcologia by Lackner et al that related Dopamine (DA) levels as measured by Eye Blink Rate (EBR) to preschoolers (3-5 yrs old) Representational theory of Mind (RTM).

The authors hypothesized that as one of the neural correlates of RTM is dMPFC, and as dMPFC has dopamine receptors and is innervated by dopmainergic projections along the dopamine mesocortical pathways , hence perhaps it is the dopamine’s tonic and phasic levels that may be correlated with and have a causal role in the preschoolers’ developing RTM abilities.

3-5 years is a critical period in which the RTM abilities are developing in a normal kid and are first found to be deficient in autistic kids. another linkage the authors seem relevant, but which I don’t agree to much, is the error -prediction theory of dopamine. They believe that ToM/RTM abilities develop when one takes into account the behavior of others and finds discrepancies in ones own knowledge and why they act based on certain different assumptions and by realizing this error of prediction modifies ones understanding of others and starts attributing a mind to them. The authors believe that phasic dopamine which has error prediction functions may be affecting RTM via this pathway too; I find that not very convincing.

However, their basic premise that tonic or baseline dopamine affects RTM abilite seems to be on firm ground and they found support for this hypothesis. They did not measure DA levels directly , but instead relied on Eye Bink Rate (EBR) which is a robuts predictor of overall dopamine in the mesolimbic pathways via the caudate nucleus dopamine levels. They also did not measure EBR directly but measured it using EEG waveforms of relevant brain regions above the eyes.

The RTM tasks they used and the Response -conflict executive function (RC-EF) tasks they used are very simple and intuitive and I refer the reader to methods section to pursue them in detail. For our purpose it is sufficient to mention that RTM did not include the famous anne-sally false belief task but had other variants like false belief location task etc.

Their findings were unequivocal. They found that DA levels as gauged from EBR were a significant predictors of RTM abilities and the effect was not mediated by a possible confound- that of RTM and RC-EF linkages and correlations.

For our purposes what is most important is the direction of the effect . More DA levels were associated with better RTM ; while lower DA was associated with lower RTM performance. This is consistent with the DA relation of Schizophrenia/Autism one of which has higher DA levels and better ToM; while the other both poorer ToM and lower baseline DA. To quote:

These findings dovetail with other research connecting dopamine and representational theory of mind in autistic and schizophrenic populations. Both autism and schizophrenia have been associated with RTM impairment (Pickup, 2008; Sabbagh,2004; Savina & Beninger, 2007) and dysregulation of DA (Braver, Barch, & Cohen, 1999; Lam, Aman, & Arnold, 2006). For instance, in the case of schizophrenia there is some evidence that increased levels of frontal dopamine, as a consequence of the pharmacological activity of some atypical antipsychotics, leads to increased performance on RTM tasks (Savina & Beninger, 2007). The present study added to this body of literature by demonstrating associations between RTM and DA in typically developing children. Considered together, this further supports the hypothesis that dopaminergic functioning plays a role in RTM development.

As always, I am excited by more support for Autism and Psychosis as opposites theory and belive this further cements the case and shows possible neurochemichal mechanisms underlying the difference.

Lackner, C., Bowman, L., & Sabbagh, M. (2010). Dopaminergic functioning and preschoolers’ theory of mind Neuropsychologia DOI: 10.1016/j.neuropsychologia.2010.02.027

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