Category Archives: schizophrenia

Badcock on Edge: the imprinted gene theory of ASD/ PSD

This edition of Edge features an article by Christopher Badcock, about the imprinted gene theory of Autism Spectrum disorders and the psychotic spectrum disorders that he has been developing with Crespi.  It is a must read and has been very nicely done.

He goes on to list the differences between autism and psychosis in a tabular form and then extends this to list the differences between mentalistic and mechansitic cognitions.

Autism/Asperger’s syndrome Psychosis/Paranoid schizophrenia
gaze-monitoring deficits delusions of being watched/spied on
apparent deafness/insensitivity to voices hallucination of and hyper-sensitivity to voices
deficits in interpreting others’ intentions erotomania/delusions of persecution
deficits in appreciating shared-attention/groups delusions of conspiracy
theory of mind deficits magical ideation/delusions of reference
deficit in sense of personal agency/episodic memory megalomania/delusions of grandeur
literalness/inability to deceive delusional self-deception
pathological single-mindedness pathological ambivalence
early onset late onset

Mentalistic Cognition Mechanistic Cognition
psychological interaction with self and others physical interaction with nature and objects
uses social, psychological, and political skills uses mechanical, spatial, and engineering skills
deficits in autism, augmented in women accentuated in autism, augmented in men
voluntaristic, subjective, particularistic deterministic, objective, universal
abstract, general, ambivalent concrete, specific, single-minded
verbal, metaphoric, conformist visual, literal, eccentric
top-down, holistic, centrally-coherent bottom-up, reductionistic, field-independent
epitomized in literature, politics, and religion epitomized in science, engineering, and technology
‘pseudo-science’: astrology, alchemy, creationism ‘hard science’: astronomy, chemistry, Darwinism
nurtured: culturally- and personally-determined natural: factually- and genetically-determined
belief-based therapies: placebos, faith-healing, psychotherapy etc. physical effect-based therapies: drugs, surgery, physiotherapy, etc.

He lists down some of the other arguments that I have made viz the fact that Valproic acid exposure in childhood/ pregnancy causes Autism, while valproic acid is used for treating psychosis. Overall it is a very interesting read and a must read.

He also tries to address the mCDD (or simultaneous occurence of Autism and Schizophrenia) in his article, though I find that part the least convincing. Here is what he has to say:

The model appears to rule out anyone suffering from an ASD and a PSD simultaneously, and such co-morbidity does appear to be rare—but is not unknown. However, I know of cases of individuals diagnosed with bipolar disorder who also show unmistakable signs of ASD during their non-manic phases. Indeed, I have research on one individual who suffers from severe gaze-aversion, autistic deficits in a sense of self and social anxiety most of the time, but who becomes comfortable with other people during manic episodes when his sense of self hypertrophies into megalomania with the feeling that he is the returned Jesus Christ! Furthermore, there is evidence of both ASD and PSD in Newton and Beethoven, and incontrovertibly so in the Nobel-prize winning mathematician John Nash. Here the theory predicts that the ASD must come first (typically in childhood) and leave a permanent savant-like basis later built on by hyper-mentalistic tendencies to produce an unusually broadened and dynamically-balanced cognitive configuration: that of true genius.

I find this fascinating and agree with Badcock that the theory leads to many predictions and all these are testable; so we are witnessing a new paradigmatic shift in our understanding of these neurodevelopmental disorders and further experiments would definitely lend more credence to this theory in my view.

Autism and Schizophrenia co-occurence

Socrates has raised an important point in one of the recent comments that if Autism and Schizophrenia are opposite poles , how do you explain their (rare) simultaneous co-occurrence?  This same question has been raised by other commentators (like Julia)  before and though I have responded in the comments, I’ll like to highlight the earlier response here for the benefit of all readers. Here is one of my earlier responses to the prevalance of mCDD and I hope to stimulate some discussion on this:

One way to look at this (mCDD) would be to treat this as similar to mixed episodes in bipolar disorder. Here both symptoms of Mania and depression are present in the same individual though traditionally Mania and depression are thought of as opposite poles on a continuum. In effect though Autism and Schizophrenia/psychosis are opposite extremes, in some individuals both may be present. However, also note the differences form mixed episodes in bipolar; there the mixed state as well as mania and depression happen in the same individual over time; here the disorders itself are simultaneously present in the individual.

Another example I can think of is of recessive alleles for both disorder at the same gene locus. (lets for example consider that eye color is due to recessive alleles at the eye-color locus). Now suppose that recessive allele S confers risk of schizophrenia and N is the normal variant. so SS is schizophrenic; SN is on the continuum toward schizophrenia and normality, perhaps a schizotypal individual. Suppose also that recessive allele A at the same locus makes one susceptible to Autism (they are opposite poles so evidently should work on same locus / loci). Thus AA is autistic and AN is asperper’s; now consider the rare scenario where one gets AS genotype ; in this case one might be asperger’s and schizotypal; in rare scenario this may develop into full-blown child-onset schizophrenia and classified as PDD_NOS or McDD.

To test my theory one can see the frequencies of Autistic and Schizophrenics and also the McDD iondividuals. If there was no interaction, Autism and schizophrenia should be independently inherited and P(mcDD) = P(Autism) * p(schizophrenia) where P is probability of an individual in a population belonging to that disorder. As my theory predicts there should be some interaction (the gene locus is same), so P(mcDD) should be different from that calculated from above (though I lack the requisite math knowledge to come up with a good formula!)

 I believe I owe a bigger response to the questions raised, but I am hoping this to turn out as more of a conversation, then a one -sided defense of my pet theory,  and would encourage more and more readers to get involved and propose new and radical solutions to this conundrum that has been highlighted!  Also any statistics on the co-occurrence and individual occurrence and prevalence of Autism and schizophrenia would be more than welcome


Decision-making research in autism and schizophrenia: Implications for each other

Today I would like to review two recent articles on decision-making: one concerned with autism or ASD and the other with Schizophrenia individuals. I would like to demonstrate how some of the findings fit in, in the larger context of Autism and Schizophrenia as diametrical poles on a continuum.

The first article is by Martino et al, and discusses a finding that those with ASD display more consistent and logical decision-making that is immune to framing effects.  Here is the abstract of the study:

The emotional responses elicited by the way options are framed often results in lack of logical consistency in human decision making. In this study, we investigated subjects with autism spectrum disorder (ASD) using a financial task in which the monetary prospects were presented as either loss or gain. We report both behavioral evidence that ASD subjects show a reduced susceptibility to the framing effect and psycho-physiological evidence that they fail to incorporate emotional context into the decision-making process. On this basis, we suggest that this insensitivity to contextual frame, although enhancing choice consistency in ASD, may also underpin core deficits in this disorder. These data highlight both benefits and costs arising from multiple decision processes in human cognition.

Here is the introduction:

Logical consistency across decisions, regardless of how choices are presented, is a central tenet of rational choice theory and the cornerstone of modern economic and political science. Empirical data challenge this perspective by showing that humans are highly susceptible to the manner or context in which options are cast, resulting in a decision bias termed the “framing effect”. We have previously shown that the amygdala mediates this framing bias, a finding that highlights the importance of incorporating emotional processes within models of human decision making. An ability to integrate emotional contextual information into the decision process provides a useful heuristic in decision making under uncertainty. This is a factor that is likely to assume considerable importance during social interactions in which information about others is often incomplete, ambiguous, and not easily amenable to standard inferential reasoning processes.

In this study, we investigated the effect of contextual frame on choice behavior of individuals with autistic spectrum disorder (ASD). Autism is a neurodevelopmental disorder characterized by deficits in social interaction, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior, interests, and activities. From Kanner’s earliest description, it has been recognized that individuals with ASD have a strong tendency to focus on parts rather than global aspects of objects of interest and are unable to integrate disparate information into a meaningful whole (weak central coherence theory).

We previously proposed that susceptibility to a framing bias reflects the operation of an affect heuristic. Here, we show that individuals with ASD, a condition characterized by marked behavioral inflexibility, demonstrate a decreased susceptibility to framing resulting in an unusual enhancement in logical consistency that is paradoxically more in line with the normative prescriptions of rationality at the core of the current economics theory. Furthermore, insensitivity in these subjects to a contextual framing bias was associated with a failure to express a differential autonomic response to contextual cues as indexed in skin conductance responses (SCRs), a standard measure of emotional processing. Our findings suggest that a more consistent pattern of choice in the ASD group reflects a failure to incorporate emotional cues into the decision process, an enhanced economic “rationality” that may come at a cost of reduced behavioral flexibility.

The experimental procedure used framing of gambles in terms of loss and gain and it is a well established paradigm that shows that normal people are risk-averse when the same gamble is framed in gain terms and risk-prone when the same gamble is framed in loss terms. Autistcis were not only more risk-averse in general , but their responses did not differ in relation to whether the frame was of loss or of gain. Thus, they were consistent in both the framing conditions. also , a measure fo their skin conductance did not show differential activation in the two frames of loss and gain; while the SCR of controls differed significantly. thus, teh authors conclude that it is the inability to take into account emotional information, that results in the consistent response of the autistics.Here is the discussion:

These findings suggest the ASD group fail to integrate emotional contextual cues into the decision-making process. This is evident both in a reduced behavioral susceptibility of a framing effect and an absence of a differential SCR response to our contextual manipulation. The concept that ASD individuals fail to integrate information across cognitive domains also informs the suggestion that an uneven profile of abilities and deficiencies in autistic individuals may reveal an imbalance in empathizing and systemizing behaviors (Baron-Cohen and Belmonte, 2005)

They discuss these findings in terms of the two-system theory of decision-making and here is what they have to say:

Recent theoretical accounts of decision making have put forward a “two-systems” model of human judgment (Evans, 2003). This view proposes that human decision making arises through a combination of intuitive and analytic processes. This model proposes that intuitive reasoning is rapid and capable of processing large amounts of information in parallel; however, it is prone to mistakes and strongly influenced by contextual emotional information (Kahneman, 2003). In contrast, analytical reasoning is more accurate but slow and computationally demanding. According to this view, the framing bias reflects an affect heuristic by which normal individuals incorporate a potentially broad range of additional emotional information into the decision process. In evolutionary terms, this mechanism may confer a strong advantage because such contextual cues may carry useful, even critical, information that dictates a rapid response. We propose that this ability is particularly crucial in a social context in that subtle contextual cues communicate knowledge elements (possibly unconscious) that allow optimal decisions to be made in uncertain environments (Stanovich and West, 2002).

In the context of the “two-systems” model of decision making described above, these results suggest that ASD individuals have an increased tendency toward the analytic type of decision making, attributable to impairment within their intuitive reasoning mechanisms. This interpretation would also support the empathizing-systemizing (E-S) theory of autism (Baron-Cohen and Belmonte, 2005). The E-S theory proposes that the imbalance between analytic and empathic behavior underlies both the impairment in social skills in ASD and their enhanced analytical skills. During the framing task, ASD subjects were better able to ignore biasing contextual information and isolate the critical information about the numerical value of the sure and risky options. This result is consistent with other experimental findings showing that ASD have enhanced attention for the task’s details but reduced capacity to deal with the global aspect of the task as predicted by weak coherence theory (Frith and Happé, 1994).

Now, I am just overjoyed reading the above. It has always been my contention that Autistics use a more deliberate, rational approach to decisions while schizophrenics are at the opposite end relying on the intuitive part. I elaborated it in the form of Maximisers and Satisficers distinction that Barry Scwatrz has proposed and extended it to include exploration and exploitation in general. In short my thesis was, and remains, that autistics are more analytical while decision-making and schizophrenics more intuitive . the former does not take the context or frames into account while making decisions while the other takes into account too much context and is susceptible to too much framing effects.

If the above thesis is correct it leads to many testable predictions:

  • 1) Schizophnrenics/ Schizotypal individuals should be more susceptible to framing effects and should show greater inconsistencies in decision-making under uncertainity as compared to controls.
  • 2) They may also show more SCR variability when different frames of loss and gain are presented to them as compared to controls.
  • 3) They may have higher baseline risk-prone behavior than controls in all conditions.
  • 4) They may have higher activation in amygdala than controls as they use affect heuristic quite frequently while making decisions.

Part of this prediction may be satisfied by this decision-making and schizophrenia study by Ludwig et al  that found decision-making dysregulation in first episode Schizophrneia patients. Here is the abstract of the study:

Studies with chronic schizophrenia patients have demonstrated that patients fluctuate between rigid and unpredictable responses in decision-making situations, a phenomenon which has been called dysregulation. The aim of this study was to investigate whether schizophrenia patients already display dysregulated behavior at the beginning of their illness. Thirty-two first-episode schizophrenia or schizophreniform patients and 30 healthy controls performed the two-choice prediction task. The decision-making behavior of first-episode patients was shown to be characterized by a high degree of dysregulation accompanied by low metric entropy and a tendency towards increased mutual information. These results indicate that behavioral abnormalities during the two-choice prediction task are already present during the early stages of the illness.

The authors used the CT paradigm and it is important to explain that a bit here:

The purpose of the CT is to quantify decision-making characteristics based on the individuals’ sequential response patterns, which result from repeated selections of different alternatives associated with an uncertain outcome. Each subject received computerized instructions. The subject’s task is to predict on which side a stimulus (a car on the screen) will appear and select a response (to match up one of 2 figures shown on the screen) accordingly. The outcome is shown for 250 milliseconds after the subject has selected as response. A new trial begins immediately after the car has been displayed. The subject is not given any information about the sequence of the stimulus presentations, i.e., whether the stimulus is presented randomly or in any kind of order. Unbeknownst to the subjects, the location of the car shown is based on the subject’s response, i.e., the subject “correctly” predicts the location of the car in 64 trials. The basic measurements consist of the subject’s response, the presentation of the car and the latency of the response selection process, i.e., the time from the beginning of the trial to the pressing of the button. For the behavioral analysis, we used nonlinear methods— described elsewhere in detail (Paulus et al., 2001)—to obtain the following key measures:

Dysregulation: Dysregulation quantifies the range of response sequence entropies during the course of an experiment.A high dysregulation value indicates that the response sequences occurring during the experiment are characterized by botho¨perseverative tendencies“ and highly unpredictable or dynamically ”chaotic” strategies.

Metric entropy: Entropy measures the “sequential order” within sequences of responses. Whereas low entropy indicates that the response sequences are highly predictable, high entropy implies highly unpredictable response sequences. Thus, predictability is a collateral measure for the degree to which sequences of responses are based on a consistent internal strategy. However,this measure does not take into account the dependence of the response sequence on external stimuli, which is measured by the cross-mutual information (see below).

Mutual information: Mutual information quantifies the degree to which the previous response predicted the current response and provides a measure of the immediate influence of the past response on the decision in the current trial.

Cross-mutual information: Cross-mutual information quantifies the degree to which the previous location of the stimulus (presentation of the car on the LEFT or RIGHT hand side) is able to predict the current response. As opposed to entropy and mutual information, this measure quantifies the influence of external stimuli on the response sequences.

Switching probability: the probability of using the simple strategy RIGHT – LEFT.

Reaction time: the time between stimulus and response.

What they observed is summarized below:

As shown above in the results section, first-episode patients performing this decision-making test, irrespective of whether they were unmedicated or recently medicated, can be observed to have (a) more dysregulated behavior, (b) a reduced metric entropy, and (c) a tendency towards increased mutual information. As a specific response behavior (d), the patients used the switching strategy more intensely (switching between pushing the right and the left button). This study has supported our main hypothesis that decision-making dysfunctions are already present in first-episode schizophrenia (or SZ) patients.

I believe the results need some explanation, and I will stick my neck out here. More dysregulated behavior in my view, is due to the schizophrenic either trying too hard to remain consistent (when in self-aware frame of mind) or trying to be unpredictable (when in other-aware and being-watched frame of mind). The reduced metric entropy can be explained similarly . Tendency towards increased mutual information is quite informative in my view. It seems that the schizophenreic is working on the basis of an internal model and is ignoring external feedback: thus his reliance on previous response.I propose that an opposite pattern would be observed in Autistics with Autistics showing no or less mutual information, as they have poor self-models; but greater cross-mutual information , as they would base their decisions more on external stimuli or feedback.

Some other predictions, keeping in mind the autism is opposite of Schizophrenia theory are:

  • 1) Autistcis should show lesser dysregulation and more rational behavior than even controls.
  • 2) autistcis should show greater cross-mutual information than controls.
  • 3) Autistcis may or may not show lesser mutual information.
  • 4) Autistcis should use less switching strategy than controls.

All these are testable predictions and I hope someone out there tests these and lets me know!
B. De Martino, N. A. Harrison, S. Knafo, G. Bird, R. J. Dolan (2008). Explaining Enhanced Logical Consistency during Decision Making in Autism Journal of Neuroscience, 28 (42), 10746-10750 DOI: 10.1523/JNEUROSCI.2895-08.2008
Cattapan-Ludewig Katja; Ludewig Stephan; Messerli Nadine; Vollenweider Franz X; Seitz Antonia; Feldon Joram; Paulus Martin P (2008). Decision-Making Dysregulation in First-Episode
Schizophrenia The Journal of nervous and mental disease, 196 (2), 157-160

Better late than never: Mainstream media rises to Autism and Schizophrenia polarity

Readers of this blog will be familiar with two of my passionate theory building exercises- the first concerned with the eight stage developmental/ evolutionary stage theories and the second being the Autism and Schizophrenia /Psychosis as opposite poles on a continuum theory. While the first premise of stage theories was recently attached by Micaheal Shermer in Mainstream media of Scientific American; the other theory seems to have caught the fancy of Mainstream Media. Two days ago there were two articles by people I admire a lot, in magazines I admire a lot, that elucidated the Autism and Schizophrenia as opposite poles theory. The first was an article by Benedict Carrey in NYT and the second was an article by Carl Zimmer in Discover magazine. The two synchronous reporting are a result of a Baddock and Crespi article in Nature , this august. But the mainstream media, as always, is late to the party when compared with the blogosphere. 

I have been proposing and promoting the Autism and Schizophrenia as opposite poles argument since the inception of this blog, but the ideas crystallized about two year back based on work of Nettle. Since then I have found evidence from different quarters including Chris Frith and Baddock and Crespi. I covered the Baddock and Crespi original article (not the Nature opinion piece) about a year back, though it didn’t find many takers at that time. I am glad that the same is finding acceptance now and is going mainstream. The Discover magazine article is really good and gives you some analysis of how gene imprinting works and how that may be instrumental in differential outcomes in the two cases of Autism and Schizophrenia and I recommend reading it as well as the NYT arcticle. If you want to read more about this theory, of course the first recommendation from me would be to read all the Mouse Trap articles labeled Autism or Schizophrenia or Psychosis. If you are more scientifically inclined, go read the original Baddock and Crespi paper amongst others. If you would just like to see the buzz in blogosphere and for some more context see the Mind Hacks article (that correctly mentions Chris Frith as a pioneer, but sadly does not mention efforts of Nettle in the same Autism-Schizophrenia model development) or see the Peter Cramer blog at In Practice from which I originally came to know of this mainstream media acceptance.

I hope that one day the eight stage model will also find the same sort of media acceptance and will lead to more stimulating work.

Autism and Schizophrenia: a minicolumnar deficit?

It has been my long standing thesis that Autism and Schizophrenia are opposite poles on a continuum; and the most recent evidence I would like to allude to is the mini columnar structure and abnormalities associetd with it in both the diseases. 

Let me at the outset, say that I am not an expert on mini-columns and hardly understand them, so would be glad if somebody corrected me or pointed out errors in the analysis.
First let me report on Schizophrenia from an abstract of a paper titled Mean cell spacing abnormalities in the neocortex of patients with schizophrenia by M Casanova et al

It has been postulated that the prefrontal cortices of schizophrenic patients have significant alterations in their interneuronal (neuropil) space. The present study re-examines this finding based on measurements of mean cell spacing within the cell minicolumn. The population studied consisted of 13 male schizophrenic patients (DSM-IV criteria) and 13 age-matched controls. Photomicrographs of Brodmann’s areas 9, 4 (M1), 3b (S1), and 17 (V1) were analyzed with computerized image analysis to measure parameters of minicolumnar morphometry, i.e., columnarity index (CI), minicolumnar width (CW), dispersion of minicolumnar width (VCW), and mean interneuronal distance (MCS). The results indicate alterations in the mean cell spacing of schizophrenic patients according to both the lamina and cortical area examined. The lack of variation in the columnarity index argues in favor of a defect postdating the formation of the cell minicolumn.

To simplify the terms, I assume that CI relates to number of minicolumns in the neocortical broadmann area under consideration; CW is generally refered to as the width of the minicolumns i.e how big a particular minicolumn is , VCW I presume is related to how widely are the minicolumns themselves spaced from each other ie. the distance between two mini-columns and the last MCS is related to how densely neurons are packed within a mini-column.
Now for Schizophrenia, what I could find on the net, seems to suggest that they have reduced MCS as compared to controls i.e the neurons of schizophrenics are more densely packed within a mini-column as compared to controls .  Also, it was found that the density was greatest in core region and lesser so in the outer neuropil region of the mini-column.
An  opposite pattern is observed in Autism. Here is the abstract of article titled: Disruption in the inhibitory architecture of the cell minicolumn: implications for Autisim. by M Casanova et al again: 

The modular arrangement of the neocortex is based on the cell minicolumn: a self-contained ecosystem of neurons and their afferent, efferent, and interneuronal connections. The authors’ preliminary studies indicate that minicolumns in the brains of autistic patients are narrower, with an altered internal organization. More specifically, their minicolumns reveal less peripheral neuropil space and increased spacing among their constituent cells. The peripheral neuropil space of the minicolumn is the conduit, among other things, for inhibitory local circuit projections. A defect in these GABAergic fibers may correlate with the increased prevalence of seizures among autistic patients. This article expands on our initial findings by arguing for the specificity of GABAergic inhibition in the neocortex as being focused around its mini- and macrocolumnar organization. The authors conclude that GABAergic interneurons are vital to proper minicolumnar differentiation and signal processing (e.g., filtering capacity of the neocortex), thus providing a putative correlate to autistic symptomatology.

Now the above clearly shows that the Autistics have an increased interneuronal space in mini-columns as opposed to normals and thus have lesser density of neurons within a minicolumn. However, they have more number of minicolumns to make up for this so that overall the number of neurons in the Broadmann area remains the same or the overall neuronal density does not differ. 
We can extend the results in other directions and hypothesize that 
1) Autistics will have increased no. of mini-columns, narrower mini-columns, narrowly spaced minicolumns and decreased neuronal density within a mini0-column as compared to controls.
2) Scchizophrenics will have lesser no. of minicolumns, wider mini-columns, widely spaced minicolumns and increased neuronal density within a mini-column as compared to controls.
Some of the above hypothesis is already supported and the rest may be in press/ under lab trials. 
What this means for in cognitive terms and how this translates to autistic and schizophrenic behaviour is another issue that I may address later (once I understand more of this minicolumn stuff!!)
D Buxhoeveden (2000). Reduced interneuronal space in schizophrenia Biological Psychiatry, 47 (7), 681-682 DOI: 10.1016/S0006-3223(99)00275-9

M CASANOVA, L DEZEEUW, A SWITALA, P KRECZMANSKI, H KORR, N ULFIG, H HEINSEN, H STEINBUSCH, C SCHMITZ (2005). Mean cell spacing abnormalities in the neocortex of patients with schizophrenia Psychiatry Research, 133 (1), 1-12 DOI: 10.1016/j.psychres.2004.11.004

Manuel F. Casanova, Daniel Buxhoeveden, Juan Gomez (2003). Disruption in the Inhibitory Architecture of the Cell Minicolumn: Implications for Autisim The Neuroscientist, 9 (6), 496-507 DOI: 10.1177/1073858403253552

Exploration/ Exploitation == Maximisers/ Satisficers?

There is an interesting research coverage at We are Only Human blog regarding whether people may have two different cognitive styles- one based on exploration of novel ideas and the other based on exploitation or focus on a particular familiar idea. The study employs evolutionary concepts and theorizes that these different cognitive styles may be a reflection of the different foraging styles that might have been selected for and relevant in EEA.

Specifically, while foraging for food in a habitat where the food supply and resources are unpredictable , one is faced with a choice when one has discovered a food source: whether to exploit this food source (a jungle area having sparse edible leaves) or to move ahead in search of a potentially better food source (a jungle area having abundant edible and nutritious fruits) . Both strategies , that of exploring or exploiting can be advantageous and may have been selected for. It is also possible that humans can use either of the strategies based on the environment- (food source distribution) , but may be inclined towards one strategy or the other. The authors of the study surmised that both the strategies have been selected for and we have the potential to use either of the strategy. Moreover, the same foraging strategy we use or are primed of, would also be visible in the cognitive strategy we use.

They used an ingenious technique to prime the subjects with either of the foraging strategies (go read the excellent We are only human blog post) and found that humans were flexible in the use of the appropriate strategy, given the appropriate context, and that the foraging strategy primed the corresponding cognitive strategy. To boot, those primed with an exploratory foraging strategy would be more prone to using exploratory cognitive strategies when confronted with a cognitive task and vice versa. They also found systematic differences between individuals cognitive and foraging styles- some were more exploratory than the others.

This reminds me of the Maximizers/ Satisficers distinction in decision-making style that Barry Scwatrz has introduced and brought to public attention. Basically a Maximizer , when faced with a decision and choice, would go on computing the utility of different choices and try to choose the option that maximizes his utility and is the ‘best’. A Satisficer, on the other hand would also explore options, but stop his exploration, when he finds an option that is ‘good enough’. I wonder, if just like the exploratory/ Exploitative cognitive and foraging styles, this is just another dimension of the same underlying phenomenon- whether to explore more – or to exploit what is available. To take an example, for marriage, a satisficing strategy may work best – as told in “The Little Prince” one should stop searching for more flowers if one has already had the fortune of possessing a flower.

“People where you live,” the little prince said, “grow five thousand roses in one garden… yet they don’t find what they’re looking for…”

“They don’t find it,” I answered.

“And yet what they’re looking for could be found in a single rose, or a little water…”

An interesting experiment would be to see, if the foraging style, the cognitive style, and the decisions style are all correlated within individuals and if priming one can influence the outcome of the other style.

If so, could there be an underlying neural phenomenon , common to all?

Wray, the author of We are only human blog makes a bold conjecture and relates this to the finding that dopamine levels.

Exploratory and inattentive foraging—actual or abstract—appears linked to decreases in the brain chemical dopamine.

He even relates this to cognitive disorders like Autism and ADHD.

By analogy, in conditions where baseline dopamine is more, like in bipolar and psychosis, one may be more inclined to a more staisficing/ ‘I’m feeling Lucky’ strategy in which the very first option is acceptable. This may explain the ‘jumping-to-conclusions’ bias in schizophrenia/ psychosis.

To make things more explicit, though the leading dopamine theory in vogue now is of ‘error-prediction’ , a competing, and to me more reasonable, view of dopamine function is incentive salience i.e. what ‘value’/ importance does the stimuli have for the person in question. The importance can be both positive and negative and thus we have found that dopamine is involved in both dread and desire. The dominant reward prediction theory faces many challenges, the least of which is response of dopamine neurons to novel events. A dopamine burst is also associated with ‘novel’ events and thus dopamine is somehow involved in/ triggered by Novelty. Baseline dopamine may constrain the dopamine surge felt on a novel event. Thus, in schizophrenia/ psychosis , with baseline dopamine high, a dopamine burst on novelty detection may be high enough so that it is meaningful and may not lead to more exploratory behavior. While in the disorders where baseline dopamine is low, one may require a more profound dopamine burst before the stimuli becoming meaningful and thus may go on seeking novel stimulus till one finds one ‘big enough to trigger salience’.

We may extend the salience argument to other domains than incentive. If the chief function of dopamine is to mark salience, then it may also be instrumental in memory and attention. Only what is Salient gets attention, and only what is salient gets into Working Memory. Thus,a high dopamine level may predispose to treating almost everything as salient, leading to delusions of reference (everything is meaningfully related to self etc) etc. Working Memory may be taxed due to everything trying to get in- and thus poor WM in people with schizophrenia. Also, every trivial thing may grab attention- leading to poor sensory gating and conditions like lack of pre-pulse inhibition. On the flip side, while making sense of ones experience, one may accept the first possible explanation and do not search further – thus leading to persistence of delusions.

An opposite scenario would be when one keeps exploring the environment and nothing seems novel due to low dopamine levels. This would be the classical Autistic repetitive and stereotype behaviors. There would be sensory over stimulation, as nothing is salient and one needs to explore more and more. On the other hand, WM capabilities may be good/ savant like, as not every piece of information grabs attention. Everything should seem insignificant and the only way to arrive at decision / choose action would be via exhaustive enumeration and logical evaluations of all options. even after obvious explanations for phenomenon, one may keep looking for a better explanation. No wonder , as per my theory, more scientists would be autistic.

Perhaps, I am stretching things too far, but to me the dopamine connection to Salience/ Meaning/ Importance is sort of worth exploring and I will write more about that in future. For now, let us be willing to associate Salience not just with stimuli related to motivation, but also with stimuli relevant in sensation, perception,learning and memory. If so the common underlying mechanism responsible for differentiating us as a exploratory and expolitatory forager (food) may also be related to our different cognitive styles, our different decision-making styles and our different baseline dopamine levels.

Dopamine though is most strongly related to food and sex. I could even stretch this argument and say this may be related to r and K reproductive styles (note these styles are species specific, but I believe individuals in a specie may also vary on the reproductive strategy along this dimension). Thus, while explorers may have r type of reproductive style, the exploiters may have a K reproductive style.

At one extreme are r-strategies, emphasizing gamete production, mating behavior, and high reproductive rates, and at the other extreme are K-strategies, emphasizing high levels of parental care, resource acquisition, kin provisioning, and social complexity.

If K-strategy is what humans have chosen, maybe exploitation in all areas (cognitive, decision-making, foraging) is more relevant and in tune with our nature. Maybe that’s why I’ll always be on the side of Psychosis than Autism!! Though, to put things in perspective, maybe humans have evolved to use both strategies as the situations demands , and the best thing would be to use the strategy situation-specific and not lean towards either extremes.

CNVs and Autism/ Schizophrenia

I had been meaning to comment on a recent paper that found that rare and de novo Copy Number Variants (CNVs) were more common in schizophrenics as compared to controls.

Copy number Variants is a type of variation in the genome of two individuals. Whole genes or big chunks of DNA may get deleted or duplicated in individuals leading to CNVs. It is important to stress that each individual has two copies of a gene. Now it might happen that the whole gene from one of the parents gets deleted leaving the individual with only one functional gene. It may also happen that one of the DNA strands, instead of having a single gene sequence, has multiple such sequences leading to duplication. These sort of duplications and deletions can also have deleterious effects. this type of variation between genomes of individuals is as opposed to the Single Nucleotide Polyphormism (SNPs) in which normally only a single base changes and this may or may not lead to change in amino acid being transcribed. The two variants of genes that differ by such a single base change are referred to alleles and we have dominant or recessive genetic disorders based on whether both genes have to be of the same deviant mutation to confer susceptibility to disease.

CNVs on the other hand present a different model of disease. One can have one or more types of CNVs (deletions, duplications, multiple duplications etc) associated with the same genetic code sequence and this in my view would lead to spectrum like diseases where one may find variations along a continuum on a particular trait- based on how many copies of the genetic sequence one has. One would remember that I adhere to a spectrum based view of schizophrenia/psychosis and also a spectrum based view of Autism. Moreover I believe that Schizophrenia and Autism are the opposite ends of the spectrum, whose middle is normalcy and that the appropriate traits may have to do with social brain, creativity etc.

now as it happen 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.

One of the readers of this blog, ‘concerned heart’, in a comment on an earlier post ,though has taken the new finding to imply that autism and Schizophrenia (especially childhood onset schizophrenia) is one and the same. Nothing could be farther from the truth. They are the same spectrum conditions and both are due to deficits in the same brain circuit/ mind module. Yet the deficits in one are the reverse of that found in the other and they are opposite ends of the spectrum. The mere fact that both involve CNVs and that too near the same chromosomal region, is not sufficient to warrant that they are the same. It would be akin to saying that because both sickle cell anemia and Huntington disease are due to SNPs , they are the same disorder. Nothing could be farther from the truth. I’m stretching the analogy too far, but this is just to stress that the role of CNVs in both the diseases do not imply that both diseases are same. However, some overlap , or even the same gene, could be involved in both Autism and Schizophrenia as they indeed are opposite ends of a spectrum. It may be like a gene for height (although life is not so simple that there is only one gene for height) —one sort of disruption of the gene may lead to dwarfism ; while the other may lead to an unusually high height.

However, I do not claim to fully understand the significance of CNVs or how they can have deleterious effects; but it is heartening to note that CNV mechanism may be a viable alternative to multiple genes coming together additively to bring about complex effects. If I understand correctly rare de novo CNV is equivalent to shearing of a single gene and could lead to deleterious effects on the scale of complex symptomatology like that of autism or schizophrenia. I’ll be watching this CNV business quite keenly, but meanwhile I stand by my position that this in no way proves that Autism and schizophrenia are the same condition.If at all it juts bolsters the argument that they are opposite disorders of the same gene/ loci/ trait/ brain system.

Autism and Schizophrenia: Chris Frith on my side

I was reading the excellent new book by Chris Frith titled ” Making up the mind: how the brain creates our mental world” and was delighted to discover that Chris Frith, a leading world authority on Schizophrenia (and whose wife Uta Firth is a world authority on Autism) also contrasts Autism and Schizophrenia along the social, mind-reading dimension.

To quote from his book:

We understand that people’s behavior is controlled by beliefs even if these beliefs are false. And we soon learn that we can control people’s behavior by giving them false beliefs. This is the dark side of communication.

Without this awareness that behavior can be controlled by beliefs, even when these are false, deliberate deception and lying are impossible. In autism this awareness seems to be lacking, and people with autism can be incapable of deception. At first thought the inability of the autistic person to lie seems to be a charming and desirable trait. But this trait is part of a wider failure to communicate, which also makes people with autism seem rude and difficult. It can often make them lonely and friendless. In practice, friendly interactions are maintained by frequent little deceptions and circumlocutions that sometimes hide our true feelings.

At the other extreme from autism lies the person with paranoid schizophrenia who is aware of intentions that are invisible to rest of us. For the person with paranoia every statement can be a deception or a hidden message that has to be interpreted. Hostile statements can be interpreted as friendly. Friendly statements can be interpreted as hostile.

One person heard voices saying “Kill yourself ” and “He’s a fool.” He described these voices as two benevolent spirits who wanted him to go to a better world. Another person heard voices saying “Be careful” and “Try harder.” These were “powerful witches who used to be my neighbours . . . punishing me.”

This hyperawareness of the intentions and feelings of other people can be so intense as to be overwhelming.

The walk of a stranger in the street could be a “sign” to me that I must interpret. Every face in the windows of a passing street car would be engraved on my mind, all of them concentrating on me and trying to pass me some kind of message. . . . The significance of the real or imagined feelings of people was very painful. To feel that a stranger passing on the street knows your innermost soul is disconcerting. I was sure that the girl in the office on my right was jealous of me. I felt that the girl in the office on my left wanted to be my friend but I made her feel depressed. . . . The intensity with which I felt [these impressions] made the air fairly crackle when the typists in question came into my office. Work in a situation like that is too difficult to be endured at all. I withdrew farther and farther.

In such a state the possibility of meeting other minds has been temporarily lost. This vivid experience of the minds of others no longer corresponds to reality. Like the person with autism, the person with paranoia is alone.

It is important to pause here and note that there are two issue involved in the concept of the social brain. In words of Frith himself:

Perhaps the most important attribute of the social brain is that it allows us to make predictions about people’s actions on the basis of their mental states. This assumption that behaviour is caused by mental states has been called taking an ‘intentional stance’ (Dennett 1987) or ‘having a theory of mind’ (Premack & Woodruff 1978). The largely automatic process by which we ‘read’ the mental states of others is called mentalizing.

Thus, the deficits (and the excesses) in Autism (and schizophrenia) with relation to the social mind may arise from deficits in both of the processes involved. I have argued earlier that Schizophrenics/ Psychotics have too much of an intentional stance and have an animistic bias, while the reverse is true of Autistics. Similarly others , based on Mirror Neuron deficits have argued that the capacity to mentalize or infer mental states of other is impaired in Autism. The capacity to infer mental state sof others may be enhanced in schizophrenics/ psychotics (thus making them better artists/ writers).

To me having the Friths on my side is very important. Chris Frith is a very engaging author and I highly recommend his book Making up the Mind to all the readers of this blog. He doesn’t tackle the question of consciousness; but on the other hand shows brilliantly – how, effortlessly and unconsciously, our brain helps us navigate the physical as well as the social world.

God is just a type I error!

Yes, believe me God is an error and that too a type I error. But before we appreciate the subtleties of that argument, we have to first learn a bit about error management theory ( not to be confused with the TMT or terror management theory about which too I have blogged previously). EMT in simple terms is an evolutionary theory that posits that we do not minimize the number of errors that are possible when we are faced with ambiguous situations and corresponding ambiguous decisions to make; but that we minimize the total costs associated with making the errors. To simplify, whenever we make a decision about reality that is based on our inferences then we can make two types of errors : in type I errors we assume/ infer something to be real, while the phenomenon is itself unreal (this is a false positive);l while in type II errors we assume/infer something to be unreal while the phenomenon is real.

To take by the way of an example , if we are in a jungle and hear a sound in a bush ; then if the sound was from a lion and we inferred that it was not from a lion we make a type II error; if the sound was not from a lion, but we infer that it was from a lion we make a type I error. Obviously in this case it is best to make a type I error as a type II error can mean death. Evolution would thus select for a behavior that is biased towards the flase positive inferences in this case.

I’ll now let Haselton define the theory and give examples:

Error management theory proposes that the direction of a bias in social judgment is tied to how costly different kinds of errors are. For example, consider how smoke alarms are designed. Failures to detect fires (false negative errors) are extremely costly, whereas false alarms (false positives) are usually just inconvenient. So, when engineers make smoke alarms, they tend design them to be biased away from the more costly false negative error by setting a low threshold for fire detection. As a consequence, smoke alarms will tend to be systematically biased toward false positive errors (false alarms). A low threshold for fire detection will cause smoke alarms to make more errors overall, but it will minimize the cost of errors when they inevitably occur (i.e., the errors will tend to be false alarms rather than missed fires).

Error management theory proposes that the same principle of design applies to the evolution of judgment mechanisms in the human mind. Ancestrally, in many areas of social judgment, the costs of false positive and false negative errors differed. When the costs of false negatives are greater, error management theory predicts a bias toward false positives (as in the smoke alarm example); when the costs of false positives are greater, error management theory predicts a bias toward false negatives.

One example of a false-positive bias is in men’s estimations of women’s sexual interest. For an ancestral man, failing to detect sexual interest in a woman resulted in a missed reproductive opportunity, which was highly costly to his reproductive success. The opposite error (believing that a woman was interested when she was not) was perhaps a bit embarrassing, but probably was less costly overall. Thus, error management theory predicts that natural selection designed a bias in men toward slightly overestimating a woman’s sexual interest in order to reduce the likelihood of a missed sexual opportunity; this leads modern men to “overpercieve” women’s sexual interest.

Satoshi Kanazawa, who has applied the error management theory to the above men-think-women-are-attracted-to-them behavior has a two part post over at his psychology today blog that is worth reading in entirety. There he argues that we believe in god, because of an inbuilt bias to detect agency. He says that detecting agency when none is there can only lead to paranoia in the worst case, while not detecting agency when there was one could lead to death. He has a beautiful figure illustrating the same and I post it here.

Different theorists call this innate human tendency to commit false-positive errors rather than false-negative errors (and as a consequence be a bit paranoid) “animistic bias” or “the agency-detector mechanism.” These theorists argue that the evolutionary origins of religious beliefs in supernatural forces may have come from such an innate cognitive bias to commit false-positive errors rather than false-negative errors, and thus overinfer personal, intentional, and animate forces behind otherwise perfectly natural phenomena.

You see a bush on fire. It could have been caused by an impersonal, inanimate, and unintentional force (lightning striking the bush and setting it on fire), or it could have been caused by a personal, animate, and intentional force (God trying to communicate with you). The “animistic bias” or “agency-detector mechanism” predisposes you to opt for the latter explanation rather than the former. It predisposes you to see the hands of God at work behind natural, physical phenomena whose exact causes are unknown.

In this view, religiosity (the human capacity for belief in supernatural beings) is not an evolved tendency per se; after all, religion in itself is not adaptive. It is instead a byproduct of animistic bias or the agency-detector mechanism, the tendency to be paranoid, which is adaptive because it can save your life. Humans did not evolve to be religious; they evolved to be paranoid. And humans are religious because they are paranoid

It is interesting to note that Kanazawa mentions the research of Nettle as I am myself a big fan of his work, but never knew that he had contributed to the EMT too. I myself have speculated on the close association of religiosity with psychosis and the Kanzawa post just bolsters the arguments there.

To sum up, it is perhaps better to be paranoid and suffer from the God delusion! You would at least survive to pass your genes along!!

Brain Feminization of males with schizophrenia?

I don’t really know what to make of Mendrek’s results as discussed in this article that claim to have discovered “masculinization” of females and “feminization” of males with schizophrenia (at least at the neuroanatomical level).

The study, that used emotive film clips and fMRI to find the pattern of activation on watching emotional stimulation in a schizophrenic population, did not have any normal controls. Thus, while the fact that their results showed greater activation in Males as compared to females may be true, they do not tell us how this is related to the activation in normal population? Are schizophrenic in general more emotional than baseline normal people or less emotional is not clear. It is presumed that the baseline normal activity falls midway from what was observed in males and females and thus males more feminized while females more masculanized.

I also do not know how to integrate this finding with my framework that sees Autism and Schizophrenia/ psychosis as opposite ends of spectrum. If we juts limit our discussion to Males, then everything seems fine. Autism is the ‘extreme male brain’ theory while schizophrenia in males is ‘feminization’ of Masculine brain. but what when we extend the ambit to cover females. should one posit that schizophrenia is characterized by movement away from gender based brain development; while Autism is characterized by movement towards gender specific brain development. In this case one would conclude that female autistics were an extreme female brain. I don’t like this argument as there seems scarce evidence for that. I would instead argue that even females in Schizophrenia are more feminized and this may have to do with the imprinting genes that we have discussed earlier. If the evidence was there that both males and females are more feminized in schizophrenia, life would be simple. Let me know what you think in comments and of any evidence you may be aware of.