genetics
Psychosis and Autism as Diametrical Disorders of the Social Brain: converging evidence!!
Jan 29th
Readers of this blog will be familiar with my model of Autism/ Schizophrenia and I recently found an online article by Crespi et al that elegantly summarizes the theory that autism and Schizophrenia are on a continuum of phenotypic variations related to cognition and the social brain.
I will be using images and text from that article heavily, so go ahead and read the original article too, which is very well-written and thought provoking.
The Authors contend that autism and schizophrenia are on a continuum where cognition is concerned with Autistics leaning towards mechanistic cognition, while schizophrenics leaning towards mentalistic cognition. This should be a familiar story to readers of this blog.
They discuss the various contrasting features of Autism and Schizophrenia. They contend that Autism is made up of three dimensions: language and communication difficulties, social reciprocity difficulties and creative or imaginative difficulties (which they term as repetitive and restricted behavior) .
They contrast this with the psychotic spectrum in which they include the three corresponding dimensions as Unipolar depression, bipolar disorder and Schizophrenia.
They then go ahead and list a variety of evidence from studies of growth, development, neuroanatomy, cognition, behavior, and epidemiology for diametric phenotypes in autism and psychosis. I reproduce below the table (click to enlarge – the tables are a must read!!) which highlights salient differences in phenotypes:
The authors have their own theory (which seems very plausible to me) regarding why Autism and Schizophrenia are diametrically opposite. This they contend is due to evolutionary arms race between the child and mother for scarce resources mediated by maternal and paternal imprinting genes.
They do a brilliant job of describing their theory so I quote from them:
Further hints that imprinted genes may have something to do with autism and psychosis come from the finding that autistics have heavier birth-weight(especially males) while schizophrenics are lighter – just as you would expect if paternal genes were more prominent in autism. Again, more paternal and/or less maternal genetic influence is sometimes implicated in cancer(another form of over-growth) and here the striking finding is that schizophrenics have less cancer than autistics despite the fact that the former smoke much more. Again, there is evidence that autistics by contrast to psychotics show early brain growth at the expense of the mother.
The article’s discussion is enlightening as it also throws light on other previous researchers who have hypothesized along similar lines. Alas The Mouse Trap doesn’t get a mention, But Nettle , regarding whom I have blogged before gets a mention.
Our hypothesis can be conceptualized at two interacting levels: (1) the diametric architecture of autistic and psychotic-spectrum conditions (Badcock 2004), and (2) the underpinnings of this structure in dysregulated genomic imprinting. A diametric structure to autism and schizophrenia has been considered for some traits before: thus, Abu-Akel (1999) and Abu-Akel & Bailey (2000) suggested that autism and schizophrenia represent extremes on a continuum of theory of mind skills from hypodevelopment to hyper-development, Frith (2004b) described ‘under-mentalizing’ in autism and ‘over-mentalizing’ in schizophrenia, and Nettle (2006) anticipated an autism psychosis spectrum in noting that “autistic traits are in many ways the converse of the unusual experiences component of schizotypy”. However, most previous research on autism and psychosis has considered the disorders to be etiologically unrelated (or has considered the negative symptoms of schizophrenia in terms of autism), although both disorders are believed to be underlain by dysregulated development of the social brain (Broks 1997; Emery 2000; Burns 2004, 2006). By our hypothesis, autism and psychosis represent extremes on continua of human cognitive architecture from mechanistic to mentalistic cognition, with balanced cognition at the center (Figure 4). Each set of conditions is extremely heterogeneous but also highly convergent, in that diverse genetic, epigenetic and environmental effects can generate similar cognitive phenotypes (Happé 1994, p. 2; Keverne 1999; Seeman et al. 2005; Badcock & Crespi 2006; Happé et al.2006). These striking convergences are mediated, in our view, by the dynamics of social brain development, with under-development in autistic conditions and hyperdevelopment in psychotic conditions (Badcock 2004), Further tests of this hypothesis should focus on assessing the breadth and depth of diametric phenotypic structure to autistic and psychotic spectrum conditions, and testing for tradeoffs between mentalistic and mechanistic thought and ability.
I am thrilled to see my theory also being investigated in parallel and worked on by distinguished scientists and am grateful for the scientific work going in this area. I am sure we will soon see more research supporting my thesis.
Nature via Nurture: IQ via breastfeeding
Nov 6th
The Nature vs Nurture debate is now old-fashioned and instead enlightened people like Malcom Gladwell have been reformulating it as Nature via Nurture where, for genes to make their impact, appropriate environmental agents have to be present. Ed Yong of the excellent Not Exactly rocket Science blog, blogs about a recent study that shows that IQ differences (of up to 7 points) in people with two different variants of a gene, FADS2, can be accomplished under the environmental conditions of breastfeeding. Thus, the gene, which is instrumental in metabolism of some fatty acids, leads to increase in IQ points, but only if the babies are breast-fed. The link seems that this gene is necessary to metabolize some of the the fatty acids present in mother’s milk.
I especially like the implications for genetics, that Yong derives from this study.
The study also has big implications for gene-hunters. The usual tactic for finding genes linked to physical traits or behaviours is to scan the entire genome for genes that have direct and prominent effects.But if the team had used this tactic, they would never have billed FADS2 as an IQ-related gene (I’m avoiding using the phrase “a gene for IQ” because it’s trite and misleading). That’s because there are no significant differences between the IQ scores of people with the two FADS2 variants if you take breastfeeding out of the equation. The upshot is that geneticists can look to the environment for important clues when looking for genes that affect human behaviour and health.
For the foreseeable future, it looks like the dichotomy of nature and nurture is dying. It’s proving to be far more interesting to look at how the two interact, and good examples are springing up fast.
Markers for Psychosis and Mania
Dec 28th
A recent review of the COMT genotype Met/VAL SNP on psychiatric phenotypes of schizophrenia, bipolar mood disorder and schizoaffective disorder seems to suggest that the SNP’s effcet mya be more of modifying the symptoms (with Val conferring positive symptom susceptibility and MET negative symptom susceptibility) of psychosis and mania, rather than conferring susceptibility to the diseases per se. Also the association, in European populations primarily, would be between both psychosis and mania (schizoaffcetive) present rather than juts a simple diagnosis of schizophrenia or bipolarity.
The narrowing of COMT linkages to the combination of Mania and Psychosis loks like a step forward and the distinction between symptom modifying effects and the distinction between symptoms based on their being positive (additions of functionality) or negative (deletion of functionality) seems to be a step in the right direction.
This differential effect of having a Met or Val allele on symptom type (positive and negative) is also inline with the inverted U model of dopamine levels that suggests that there is a range of dopamine levels that is good for the body(brain) and beyond either end there are deleterious effects. It could be that while a Met allele confers protective advantage for positive symptoms, it is an aggravator for negative symptoms. Depending on dopamine environmental levels, the person having Met allele may or may not show the symptoms of mania/ scizophrenia.
I am also intrigued by the BDNF met/val allele effect on anxiety susceptibility and forced to think whether there too the effect may be that of symptom modification rather than susceptibility?
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The Two Cultures continued
Nov 28th
While my original post regarding the two cultures of Schizophrenia and Autism was a reference to the Arts and Science cultures of CP Snow, this post is about the cultures in the traditional sense- the American culture pitted against the East Asian culture.
To recap the differences in Autism and Schizophrenia, the difference could be summarized as a linear, literal, realistic, detail-oriented and routine -bound thinking style in Autism and a non-linear(parallel), metaphorical, imaginative, meaning-oriented and novelty preferring thinking style associated with schizophrenia. One of the prime reasons for these differences was hypothesized to be a central coherence tendency in autism (too much focus on foreground and piece-meal perception/ conception) on the one hand and a contextual, broad and loose association tendency in schizophrenia (too much focus on background and a gestalt and holistic sort of perception/ conception) on the other hand.
One can even go a step ahead and characterize the autistic cognitive style as Analytical and the schizophrenic style as Holistic in nature.
That brings us to an interesting hypothesis. It is well known that cultures differ in their cognitive thinking style and it has been demonstrated in a number of studies that the American culture is characterized by an analytical thinking style, while the East Asian cultures are characterized by a holistic cognitive style.
This cross-cultural differences in cognitive style, as popularized by Richard Nisbett’?s book The Geography of Thought, has been found to be displayed in perception ( differences exist in change-blindness based on foreground/background salience and this also correlates with the differential patterns of eye fixations on background/foreground in the two cultures) , in categorization and representations(with either a style based on ecological or habitat-based thinking dominant or a one based on narrow self focus and goal-directed thinking dominant), in thinking (analytic vs holistic thinking), in reasoning about causes ( limited, direct causes vs. a large number of indirect causes) and recently in reasoning about consequences ( with western culture favoring a more direct consequence on an immediately succeeding event and the eastern cultures favoring more indirect consequences on more futuristic events and event effects on the the ultimate outcome).
Various theories have been proposed for these differences including a fear of isolation theory that posits that difference in dialectical vs analytical thinking or the reliance on context for memory recognition is due to the fear of social ostracizing, which causes one to focus more on context; a complex and ambiguous physical environment theory which in a roundabout (and in my view in a flawed) way argues that differences in complexity and ambiguity of towns and city scenes of the two cultures cause the different thinking styles rather than it being the other way round; to this being due to linguistic effects (just like this study which shows that linguistic differences cause changes in spatial cognition, I’m sure there are studies that attribute the different cognitive styles to linguistic effect) or due to genetic differences.
While I will not address the reasons for the differences, I will take as granted the fact that there are reasonable differences in the cognitive style on the figure-ground, details-gestalt and analytical-holistic dimensions and these dimensions are more or less the same sort of cognitive style differences that one sees in schizophrenia and autism.
Consistent with this cultural trend, one can predict that in cultures which favor divergent, contextual and holistic thinking , a schizotypal subject would be less susceptible to be labeled as a mentally ill person. These cultures would be more tolerant of this form of thinking and more accommodating of the extreme manifestation. consequently one can hypothesize that in East Asian cultures the incidence and prevalence of Schizophrenia would be way below that in American cultures. This is actually the case with lifetime prevalence in Asian countries being 0.25 as opposed to 0.88 for non-Asian countries.
A reverse trend would be expected in Autism, with American children being diagnosed with autism lesser than the Asian cultures. The results for this prediction are not that optimistic as data on autism prevalence in china is not readily available; but Japanese show an upward trend, while American incidence levels seem to have actually decreased over the years.
Thus, it may actually be the case that autism and schizophrenia signify the Two Cultures.
Before I part, just a parting note on the recently discovered Television and Autism linkage. John Hawks, had commented on the eye movement cultural differences study and in its context had hypothesized that the reason for differences in cognitive style with Americans focusing on the foreground object may be due to the high prevalence in America of cartoon TV viewing which causes one to focus on a one moving object, against a static background.
But let’s consider what some of those cultural reasons might be. For example, have American graduate students watched cheaply-animated cartoons for a greater proportion of their lives. You know, the kind of cartoon where the only moving object is the main character, and the background is entirely static for minutes? For that matter, does television viewing in general affect attention.
To me this hypothesis of TV-cartoon viewing and the consequent figure-focus or central coherence seems very promising and might be the reason as to why Autism is rising with increased TV viewings.
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Schizophrenia and Autism: The Two Cultures.
Nov 23rd
Mind Hacks has highlighted two posts from the BPS Research Digest that highlight the work of Daniel Nettle, related to Scizotypy and evolutionary benefit especially the linkages between schizotypy and artistic creativity.
To recap the schizotypy dimensions:
- Unusual experiences: The disposition to have unusual perceptual and other cognitive experiences, such as hallucinations, magical or superstitious belief and interpretation of events . In the clinical form manifests as positive symptoms of hallucinations and delusions.
- Cognitive disorganization: A tendency for thoughts to become derailed, disorganized or tangential. In the clinical form manifests as the positive symptoms of disorganized speech and flight of ideas.
- Introverted anhedonia: A tendency to introverted, emotionally flat and asocial behavior, associated with a deficiency in the ability to feel pleasure from social and physical stimulation. This manifests clinically as the negative symptoms of flattened affect,alogia and avolition.
- Impulsive nonconformity: The disposition to unstable mood and behavior particularly with regard to rules and social conventions. Manifests clinically as disorganized and socially inappropriate behavior like dressing inappropriately.
To summarize the key findings of the first Nettle paper:
- Unusual Experiences dimension (in general population) correlated positively with number of partners and mating success. This relationship was mediated by creative activity. Thus, unusual experiences are hypothesized to lead to creative activities, which in turn increase reproductive fitness.
- Impulsive Nonconformity had a direct positive correlation with number of partners and mating success. It independently led to increase in reproductive fitness and the effect was not mediated via creative activity.
- Introvertive Anhedonia decreases creative activity, and also has a direct negative effect on mating success.
- Cognitive Disorganization seemed to had no significant effect on mating success.
- Thus, while part of the reason for continuing prevalence of schizophrenia/schizotypy may be explained by the direct effect of Impulsive Non-conformity on Mating Success, the other part can only be explained by the benefits of creative activity that are conferred by Unusual Experiences.
As Introverted Anhedonia has a negative effect on both creative activity and mating success, it seems reasonable to posit, that while schizophrenia patients may suffer from the negative interaction between Unusual Experiences and Introverted Anhedonia; some of their relatives may benefit from the unusual experiences, while being spared from the effects of Introverted Anhedonia, and thus be specially selected for mating success that is mediated by creative activity. This creative advantage that the relatives of schizophrenia have, may have led to the fixation of this disorder in humans.
The second nettle paper explores the relationship between schizotypy and artistic creativity. the key finding here are:
1. Poetic creativity:
- Unusual Experiences score increase in a significant manner from non-poets, to hobbyists to serious poets. It slightly decreases with professional poets.
- The same trend is shown by Impulsive Nonconformity and Cognitive Disorganization.
- Introverted Anhedonia, on the other hand, shows a non-significant trend to decrease with increasing creative activity.
2. Visual art creativity:
- The trends for Unusual Experiences, Impulsive Nonconformity and Cognitive Disorganization are the same as in case of poetry, the only difference being that Cognitive Disorganization trend is not significant.
- Introverted Anhedonia, on the other hand, shows a significant trend to decrease with increasing creative activity.
3. Mathematical creativity:
- The trends are opposite to that of poetic and visual arts creativity in this case.
- The scores for Unusual Experiences, Impulsive Nonconformity and Cognitive Disorganization decrease with mathematics engagements level.
- The scores for Introverted Anhedonia, increase and correlate with mathematical activity.
4. The conclusion is that schizotypal traits like Unusual Experiences, Impulsive Nonconformity and Cognitive Disorganization are instrumental in creative thinking and thus have beneficial effects of stimulating creativity. Though the effect size of Unusual Experiences is the strongest, other traits also have significant effects. Increasingly serious creative engagement is associated with a decrease in introvertive anhedonia and this negative trait is thus a liability.
The authors thus conclude:
The findings provide some support for the two-factor model of Barron (1972). Creative groups are as high as patients on unusual experiences and cognitive disorganization, but lower than controls on introvertive anhedonia. Thus, artistic groups and psychiatric patients share divergent thought, but they differ in that the latter are troubled with negative symptoms such as avolition and anhedonia, whilst the former are unusually free of these traits. This is also congruent with Schuldberg’s findings that creativity scores are positively correlated with scales of positive psychotic or hypomanic symptoms, and negatively.
This, the author had hypothesized earlier in the paper, might be an alternative to an inverted-U model of benefits provided by Schizotypal traits.:
An alternative possibility comes from the two-factor approach of Frank Barron. Barron (1972) argued that successful creativity combines deviant and psychopathological traits with high scores on measures of ‘Ego strength’. Ego strength includes resilience, ability to cope with stress, self-control and high levels of experienced well-being. Ego strength is thus a mediating factor that determines whether schizotypy is translated into damaging symptoms or healthy creative output. Schuldberg’s(1990) work is relevant to this model, finding as it does that scales based on positive symptoms correlate positively with creativity scores, whereas scales based on negative symptoms correlate negatively. Thus, a lack of negative symptoms would appear to be equivalent to high ‘Ego strength’ in Barron’s terms. The prediction in terms of the O-LIFE dimensions would therefore be that creativity would be associated positively with unusual experiences but negatively with introvertive anhedonia.
He further tries to correlate this with the ‘systemising’ theory of autism:
This profile supports the picture of the mathematical mind as having opposite features to the artistic one, with a narrow range of associations (low unusual experiences), an interest in order (low cognitive disorganization), and in routine (low impulsive nonconformity). These findings are consonant with Baron-Cohen’s work on systemising as a core feature of autistic spectrum disorders. Systemising is a cognitive style characterized by a drive for order and regularity, which is elevated in high-functioning autism and in mathematics and engineering (Baron-Cohen et al., 2003; Baron-Cohen et al., 2001). The constellation of autism, systemising and science appears to be in many respects the opposite tail of the distribution to the constellation of arts, unusual experiences and affective and psychotic disorders explored in the present study.
The authors, also present the following theory of autism:
Autistic traits are in many ways the converse of the unusual experiences component of schizotypy. Whereas schizotypal thought is characterized by often metaphorical leaps from domain to domain, remote associations, and broad attentional set, autism is characterized by narrow interests and liberality, with occasionally highly developed abilities in tasks requiring systematic and convergent thinking.
I believe they have stumbled on a very important conceptualization. I myself had been contemplating the Schizophrenia- Autism linkages for quite some time. In my view, the contention that Schizophrenia reflects aspects of artistic creativity, while Autism may reflect aspects of mathematical creativity is a positive diversion form the usual male/female systematizing/empathizing spin on Autism. It is instructive to note, that while Autism is a predominantly male illness, prevalence of Schizophrenia too, is greater in Males compared to females. thus, a simple Male- Female dichotomy does not work.
I do believe that there are theory-of-mind deficits in Autism and these are responsible for their social difficulties, and this may be the opposite of the empathetic brain, but that deficit in empathy should not be construed as equivalent to a positive endowment with systematic thinking. In my view, the empathy defect is independent of the other defects like communicative and repetitive and stereotyped behavior defects. The empathy defect has to do with emotions and feelings, while the other defects might be cognitive and behavioral in nature.
Both Schizophrenia and Autism are spectrum disorders, and hence we will consider differences between the spectrum.
Let me now address the differences in Autism and Schizophrenia spectrum :
- Literal vs Metaphorical thinking. One of this blog’s reader, Mrs Mc Ewen, had recently left a comment on this site and I discovered that she is a mother of two autistic kids and maintains a blog related to that. I found one of the entries related to Literal interpretation in autism both humorous, informative and sad at the same time. On the other hand, I am well acquainted with the metaphorical thinking indulged in by schizophrenics (I’ve written a sort of Novella that revolves round that theme), and as I find the Conceptual Metaphor Theory for linguistic semantics full of promise, I have no trouble understanding the language developmental delay in Autism, or the literary/ artistic creativity of Schizotypal pro band. After all, much of art is using symbolism, metaphor etc and involves non-literal interpretation. This difference alone can account for the communication deficits faced by Autistic children. This is related to the schizotypy dimension Unusual Experiences.
- Convergent Vs Divergent thinking: Schizophrenia spectrum is marked by cognitive disorganization, flights of ideas and looses associations. It is also marked by including too much of context and in pathological cases characterized by an effort to relate each and every happening to some preexisting context (if the context is of Paronia- every event is a conspiracy; if the context is of grandeur, every event is significant and referring to self). Autistic spectrum, is not only marked by the absence of these and a low score on the corresponding schizotypal trait; but by an opposite tendency of Central Coherence. there is some research that indicates, that Autistic children show both perceptual and conceptual central coherence: i.e. a tendency to only focus on one piece at a time and an inability to use gestalt perception or conceptualization whereby one could indulge in a top-down ‘imaginary’ assembly of fragments to identify an object. thus, they take , too little of context, in my view and make lesses association than desired. One can also hypothesize, that would yield lesser scores than controls and definitely lesser scores than schizophrenics on the unusual/ novel object uses task. This may also partially explain symptoms like circumscribed and specialized interests in autism. This is related to Schizotypy dimension Disorganized Thinking.
- Reality vs. Fantasy (imagination) orientation: This relates to whether one has an ability to indulge in make-believe or in activities like pretend play. I believe that this propensity to use imagination may be linked to the unusual experiences like hallucinations that are found in schizophrenics. Magical thinking, involving endowing inanimate objects like Voodoo dolls or lucky charms, with causative powers may be converse of the autistic inability to differentiate between animals and inanimate objects, or to easily learn to distinguish between self-intended motion of a human/ animal and a pushed or caused motion of an inanimate object. It is instructive to pause here, and reflect, that much of human Agreeableness and Empathy also has to do on make-believe. One may not always love one’s friend, but out of respect and social courtesy, one would always pretend to do so. The reality orientation of autistic children, (apart form any empathy/ mirror neuron defects) may also underlie their social difficulties like inability to make friends and impaired social play. This is related to the schizotypy dimension Unusual experience.
- Routine and order Vs. Novelty preference: Autistic children are characterized by repetitive and stereotyped behavior. Schizophrenia spectrum on the other hand is high on Openness to Experience and usually display preferences for reckless, novel, socially inappropriate and sensation seeking behavior. This difference may underlie the stereotyped behavior like rigidity exhibited by autistic children. This is related to schizotypy dimension Impulsive, Nonconformity.
Overall, one possible mechanism underlying these differences can be a sensori-motor and conceptual gating defect in both the disorders- with schizophrenia signifying a very broad sensori-motor and conceptual gate with consequent broad attentional span, loose associations and too much of context; and Autism representing a very narrow spatial and temporal gate with consequent specialized interests and focus, few associations, literal and convergent thinking.
If one couples this with the phenomenon of pre-pulse inhibition (defect of schizophrenia) , then it may be theorized that as a schizophrenic would interpret all stimuli in a novel way (presentations of a stimuli earlier, does not lead to its memory or the suppression of the startle response), hence it would also develop preference for, or at least not be intimidated by, a novel item. On the other hand, due to the smaller sensory gate, and normal PPI, the autistic children would mostly be exposed to the smae stimuli over and over gaian and may develop a preference for it over any new stimuli which, when gated through its small gate, would cause it to get startled. I am even tempted to theorize that autistic children may have a high PPI than normals, but a quick Google search didn’t corroborate my speculations.
Lastly, a discussion of Anhedonia, and how that interacts with positive schizotypy and autism will need some more thinking and conceptualization. For now, I am tempted to posit that Anhedonia may be one of the dimensions of the female counterpart of Schizotypy-Autism thinking styles. Females, I believe, are more prone to depression (the primary correlate of Anhedonia) and maybe just like a Schizotypy-Autism spectrum that is along cognitive thinking styles; there might exist a Depersonlization-Bipolarity spectrum that runs along the emotion-motivation feeling styles and may reflect the two fundamental styles of emotional processing- one involving use of too much emotion and motivation (bipolarity) and the other characterized by lack of emotion and motivation (depersonalization).
While creativity (thinking) of both types (scizotypal-autistic or artistic-scientific), might have been selected by sexual selection in males; the corresponding traits that would be under sexual selection for females might be virtue/aesthetics (feeling) of both types: one subjective and based on personal constructs of emotions and motivations and the other objective and based on utilitarian concerns and needing one to put aside one’s own feelings and emotions.
Just a speculation. Do let me know, your views and opinions (or any supporting researches)!
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