Category Archives: schizophrenia

A Schizophrenia quiz

I always believe that questions and quizzes are an integral part of learning and retaining new information. So from now on , I’ll be regularly posting some quiz questions on a particular topic on the left had side bar of The Mouse Trap. You have to click on the ‘next question’ button to get at the first question. Then you have to click the buttons on the top of each alternative for the correct answer. The tool keeps track of your number of tries and correct responses and also provides explanations for the correct answers.

I intend to use this tool extensively in the future. do let me know, whether you find the tool useful and would love to see similar quizzes hosted on the Mouse Trap.

I know that many of you read the Mouse trap as part of an RSS blog reader. However, I would request you to visit The Mouse Trap and give this a shot.

Autism, the middle cingulate and reputation management

There was an article on which I had wanted to comment earlier. the study by Chiu et al shows that in autistic individuals the middle cingulate cortex is hypofunctional during the self phase of the iterated Trust game, wherein one has to infer the mind of another, decide whether to trust him or her and accordingly decide what money to give to the trustee and what to keep for oneself.

Recent work using the multiround trust game has identified activations along human
cingulate cortex consistent with agent-specific response patterns generated during interpersonal exchange with another human. These patterns differentiate outcomes following revelation of the partner’s decision (‘‘not self’’ or ‘‘other’’ response) from those following submission of one’s own decision (‘‘self’’ response). Remarkably, the patterns are spatially complementary , and almost no manipulation perturbs them except one: the removal of the interactive partner . Removal of the social partner causes the cingulate response patterns to disappear even though the sensory, motor, and reward elements of the task remain intact. These results from the trust game are consistent with agent specific cingulate responses observed in a range of other experiments. Anterior and posterior cingulate activation occurs in response to the revelation of decisions of others in two-person games like the Ultimatum and Prisoner’s Dilemma games. Furthermore, increased middle cingulate activation is commonly observed in response to one’s own social decisions or emotions.

Chris and Uta Frith do an excellent job of putting these findings in perspective and argue that the autistic is less concerned with reputation management (as it has inability to infer others mind states it does not care hat they think) and suggest a simple experiment that could elucidate the point.

Our speculation is that this process of reputation management is impaired in autistic individuals, because it depends on the ability to read the minds of others. This hypothesis can be tested experimentally. If we are concerned with our reputation then our behavior will be strongly affected by whether or not an audience is present to observe our actions. Consider, for instance, another sharing game known as the dictator game. One player is given $100 and is allowed to share any amount he or she chooses with the other player. In this situation, the rational thing to do would be to give the other player no money at all, because the second player is powerless to respond. Even “dictators” will typically dole out a small proportion of the money, however. When there is an audience for the transaction, dictators give away even more money. Presumably, they do not want to have a reputation for meanness or for acting unfairly. If autistic people are not concerned with their own reputation, then their behaviour should not be affected by the presence of an audience.

I would like to extend their experiment and suggest one for those susceptible to psychosis. I have argued that Autism and Schizophrenia/ psychosis are extreme ends of a continuum and would thus conclude that in the iterated trust game, psychotics/ those susceptible to psychosis would show hyperfunctioning of middle cingulate cortex. I have elsewhere already argued that Psychotics have an enhanced ToM or mind reading ability. I would also hypothesize that psychotics would also show enhanced reputation management and an enhanced donation of money in the trust game when an audience is present as compared to controls or the autistics.

While an experiment is the best to settle such conjectures, it is tempting to see how this adds up and can explain certain symptoms of psychosis/ mania. If one is overly concerned with reputation management one can end up being a spendthrift / show irresponsible financial behavior as one tries to build a hypothetical reputation in the minds of the audience. Taken with the fact that psychosis comes clubbed with a belief in supernatural agents, magical thinking and super agency detection etc, one may not even need an actual audience – a make-believe audience may suffice to make one get overly concerned with reputation management and thus trusting too much the others -even with their money. when reality proves otherwise and people prove to be not worthy of the trust, one may dissociate with reality altogether and become paranoid on the other extreme. We know that the ACC is dysfunctional in schizophrenics, what about the middle cingulate? is it hypoactive during trust games in the self condition? Only a hypothesis, but worth investigating!

Psychosis and Autism as Diametrical Disorders of the Social Brain: converging evidence!!

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.

Auitsm, Valproate and Mania/Psychosis

There is a new open source journal available called Frontiers in Neuroscience , and in the first edition there is an article expounding autism as an Intense world syndrome. It is a very intriguing article that claims amongst other things that autistics have very rich local neural circuitry (perhaps in lieu of sparse global circuitry) and this may be the reason why they have rich modular cognitive abilities like memory etc. I am tempted to contrast this with Schizophrenia/ psychosis where there may be more global processing of information. But before my main thesis an abstract of the paper.

Autism is a devastating neurodevelopmental disorder with a polygenetic predisposition that seems to be triggered by multiple environmental factors during embryonic and/or early postnatal life. While significant advances have been made in identifying the neuronal structures and cells affected, a unifying theory that could explain the manifold autistic symptoms has still not emerged. Based on recent synaptic, cellular, molecular, microcircuit, and behavioral results obtained with the valproic acid (VPA) rat model of autism, we propose here a unifying hypothesis where the core pathology of the autistic brain is hyper-reactivity and hyper-plasticity of local neuronal circuits. Such excessive neuronal processing in circumscribed circuits is suggested to lead to hyper-perception, hyper-attention, and hyper-memory, which may lie at the heart of most autistic symptoms. In this view, the autistic spectrum are disorders of hyper-functionality, which turns debilitating, as opposed to disorders of hypo-functionality, as is often assumed. We discuss how excessive neuronal processing may render the world painfully intense when the neocortex is affected and even aversive when the amygdala is affected, leading to social and environmental withdrawal. Excessive neuronal learning is also hypothesized to rapidly lock down the individual into a small repertoire of secure behavioral routines that are obsessively repeated. We further discuss the key autistic neuropathologies and several of the main theories of autism and re-interpret them in the light of the hypothesized Intense World Syndrome.

The authors use the valproate model of autism for their discussion and it is a well established mouse model of autism. In this model, mother rats are given valproate during pregnancy and the children later had autistic syndromes and were developmentally retarded. There is also some literature documenting a linkage between fetal valproate syndrome and autism.

Rodier et al. have reported that, in a rat model for teratogen exposure, the administration of valproic acid in early development induces morphological brainstem pathology similar to changes sometimes observed in autism. Alterations in the distribution of serotonergic neurons in brain, suggestive of abnormal neuronal differentiation and migration, have also been observed in the animal model. Further work in rats has shown that the prenatal challenge with valproic acid induces behavioral changes, including delayed maturation, decreased social exploration, deficits in sensorimotor gating, and repetitive, stereotyped responses in an open field. In mice, exposure to valproic acid while in utero leads to behavioral retardation and regression during neonatal and juvenile development

Thus from the above discussion it is apparent that exposure to valproic acid has something to do with autism. It is to be noted that valproic acid/ sodium valproate is a well-known anti-convulsant that is also given in bipolar disorder as a mood stabilizer. Now readers of his blog will be familiar with my model of autism , whereby I stress the opposite polarity to schizophrenia/ psychosis. I believe that what we witness in Autism is the converse of what we witness in psychosis. Both are pathological states, but one with too much reality orientation (including not attributing agency to fellow humans/ animals) while other too much fantasy orientation (with tendency towards anthropomorphism). Also while autistics may be the proverbial detail-oriented missing forest for the trees sort of people, schizophrenics are more meaning-and-big-picture-obsessed people with possibly more hyper-active and hyper-plastic global neural circuitry as opposed to what is hypothesized in autistic intense world syndrome.
I also consider bipolar and schizophrenia to be closely related and am not surprised that while lack of valproic acid is used to treat the bipolar psychosis and the bipolar condition; an exposure to the same teratogen during pregnancy ( a critical developmental window ) may have the opposite effect of leading to the opposite disorder like autism. To me this valproic acid linkage proves further that autism and schizophrenia/ psychosis are opposite of each other.

Basal Ganglia: action selection, error prediction and reinforcement learning

The December edition of Dana Foundation’s online brain journal , cerebrum , has a very informative and interesting piece on the role of basal ganglia in response selection, error prediction and reinforcement learning.

The article contains a primer on basic basal ganglia functions and pathways.

The basal ganglia are a collection of interconnected areas deep below the cerebral cortex. They receive information from the frontal cortex about behavior that is being planned for a particular situation. In turn, the basal ganglia affect activity in the frontal cortex through a series of neural projections that ultimately go back up to the same cortical areas from which they received the initial input. This circuit enables the basal ganglia to transform and amplify the pattern of neural firing in the frontal cortex that is associated with adaptive, or appropriate, behaviors, while suppressing those that are less adaptive. The neurotransmitter dopamine plays a critical role in the basal ganglia in determining, as a result of experience, which plans are adaptive and which are not.

Evidence from several lines of research supports this understanding of the role of basal ganglia and dopamine as major players in learning and selecting adaptive behaviors. In rats, the more a behavior is ingrained, the more its neural representations in the basal ganglia are strengthened and honed. Rats depleted of basal ganglia dopamine show profound deficits in acquiring new behaviors that lead to a reward. Experiments pioneered by Wolfram Schultz, M.D., Ph.D., at the University of Cambridge have shown that dopamine neurons fire in bursts when a monkey receives an unexpected juice reward. Conversely, when an expected reward is not delivered, these dopamine cells actually cease firing altogether, that is, their firing rates “dip” below what is normal. These dopamine bursts and dips are thought to drive changes in the strength of synaptic connections—the neural mechanism for learning—in the basal ganglia so that actions are reinforced (in the case of dopamine bursts) or punished (in the case of dopamine dips)

In particular it discusses the role of dopaminergic receptors in the GO and NoGO pathways that are involved in positive and negative reinforcement learning respectively.

Building on a large body of earlier theoretical work, my colleagues and I developed a series of computational models that explore the role of the basal ganglia when people select motor and cognitive actions. We have been focusing on how When the “Go” pathway is active, it facilitates an action directed by the frontal cortex, such as touching your pinkies together. But when the opposing “NoGo” pathway is more active, the action is suppressed. dopamine signals in the basal ganglia, which occur as a result of positive and negative outcomes of decisions (that is, rewards and punishments), drive learning. This learning is made possible by two main types of dopamine receptors, D1 and D2, which are associated with two separate neural pathways through the basal ganglia. When the “Go” pathway is active, it facilitates an action directed by the frontal cortex, such as touching your pinkies together. But when the opposing “NoGo” pathway is more active, the action is suppressed. These Go and NoGo pathways compete with each other when the brain selects among multiple possible actions, so that an adaptive action can be facilitated while at the same time competing actions are suppressed. This functionality can allow you to touch your pinkies together, not perform another potential action (such as scratching an itch on your neck), or to concentrate on a math problem instead of daydreaming.

But how does the Go/NoGo system know which action is most adaptive? One answer, we think (and as you might have guessed), is dopamine. During unexpected rewards, dopamine bursts drive increased activity and changes in synaptic plasticity (learning) in the Go pathway. When a given action is rewarded in a particular environmental context, the associated Go neurons learn to become more active the next time that same context is encountered. This process depends on the D1 dopamine receptor, which is highly concentrated in the Go pathway. Conversely, when desired rewards are not received, the resulting dips in dopamine support increases in synaptic plasticity in the NoGo pathway (a process that depends on dopamine D2 receptors concentrated in that pathway). Consequently, these nonrewarding actions will be more likely to be suppressed in the future.

It then goes on to consider the different types of learner: positive learners that have a more active GO system and negative learners that have a more active NoGO system.

This theoretical framework, which integrates anatomical, physiological, and psychological data into a single coherent model, can go a long way in explaining changes in learning, memory, and decision making as a function of changes in basal ganglia dopamine. In particular, this model makes a key, previously untested, prediction that greater amounts of dopamine (via D1 receptors) support learning from positive feedback, whereas decreases in dopamine (via D2 receptors) support learning from negative feedback.

They then experimentally manipulated the dopamine levels and verified their predictions. The experiment involved a simple game in which two symbols say A and B were paired consistently (along with other symbols say ‘CD’) with subjects required to choose one of them. After each choosing, the subject was given feedback as to whether he had been rewarded or punished. This feedback was not consistently related to the choice : ‘A’ was rewarded with positive feedback 80% of times, while ‘B’ was punished with negative feedback 80 % of the times. Thus though an implicit learning would happen to chose A and reject B, this rule would not be explicitly learned. Now, comes the interesting part, choose A strategy is related to positive learning and Avoid B strategy with negative learning. When these symbols A and B, in test phase were paired with new symbols say E and F respectively, subjects should have implicitly still gone with choose A and Avoid B strategy with equal inclination. Yet, administering dopamine affecting drugs had dramatic effects.

We found a striking effect of the different dopamine medications on this positive versus negative learning bias, consistent with predictions from our computer model of the learning process. While on placebo, participants performed equally well at choose-A and avoid-B test choices. But when their dopamine levels were increased, they were more successful at choosing the most positive symbol A and less successful at avoiding B. Conversely, lowered dopamine levels were associated with the opposite pattern: worse choose-A performance but more-reliable avoid-B choices. Thus the dopamine medications caused participants to learn more or less from positive versus negative outcomes of their decisions

They then go on to apply these results to Parkinson’s patients.In Parkinson’s patients have deficits in basal ganglia dopamine levels – especially in the NoGO pathway. Medication is L-Dopa which is a dopamine precursor and acts by increasing dopamine in the basal ganglia. They hypothesized, that people with untreated Parkinson’s will be negative learners (less dopamine and less the dip), while those on medication would be positive learners 9more dopamine and more the burst).

To test this idea, we presented people with Parkinson’s disease with the same choose-A/avoid-B learning task once while they were on their regular dose of dopamine medication and another time while off it.8 Consistent with what we predicted, we found that, indeed, patients who were off the medication were relatively impaired at learning to choose the most positive stimulus A, but showed intact or even enhanced learning of avoid-B. Dopamine medication reversed this bias, improving choose-A performance but impairing avoid-B. This discovery supports the idea that medication prevents dopamine dips during negative feedback and impairs learning based on negative feedback

This notion might explain why some medicated Parkinson’s patients develop pathological gambling behaviors, which could result from enhanced learning from gains together with an inability to learn from losses.

The above (gambling in those on dopamine) I have touched earlier also, in relation to psychosis and schizophrenia, where dopamine excess is suspected. In those cases, having a consistently high dopamine level may predispose towards positive behavioral learning and positive cognitive learning. The latter may be the underlying manic loop, whereby only positively rewarded cognitions become salient, leading to a rosy picture of universe. Negatively reinforced cognitions are not registered properly and not learned/ remembered.

They then go on to discuss other implications like in ADHD, wherein the total noise in dopamine neurons may be higher, leading to both lowered positive and negative learning (my conjecture, not author’s) and in addiction.

Overall a very fascinating article indeed.

cortex maturation: found the references

In my earlier post on cortex maturation, I was unable to find the references for the claims that in Autism cortex matures earlier during toddler phase and that even in adulthood, it may be thicker.

In a recent PNAS commentary, reagarding the delay rather than deviance theory of ADHD, I came across the appropriate references to back the above observations, as well as the accelerated pruning in child-onset schizophrenia. Passing that along.

An important question is whether the delay of brain maturation is a specific characteristic of ADHD or is shared by other child psychiatric disorders. So far, none of the other major psychiatric disorders have been associated with a maturational delay of brain structure. However, to my knowledge, longitudinal structural studies have been conducted only in patients with ADHD, childhood-onset schizophrenia (COS), and autism, finding maturational deviance rather than delay. Adolescents with COS are characterized by a striking nonlinear, progressive acceleration of the normal gray matter and volume decrease in cortical regions that levels off in adulthood (22). In autism, there is an early left hemispheric overgrowth of gray and white matter at young toddler age with conflicting findings of either arrested growth or remaining brain enlargement in adolescence and adulthood (23). The findings of delayed structural brain maturation seem, thus far, to be specific to ADHD and may be an important neuroanatomic trait. However, further exploration of the developmental trajectories in other child psychiatric disorders is needed to establish the importance of a delay of brain maturation as a specific neuroanatomic marker for ADHD.
(emphasis mine, references below)
22. Greenstein D, Lerch J, Shaw P, Clasen L, Giedd J, Gochman P, Rapoport J, Gogtay N (2006) J Child Psychol Psychiatry 47:1003–1012.
23. Bashat DB, Kronfeld-Duenias V, Zachor DA, Ekstein PM, Hendler T, Tarrasch R, Even A, Levy Y, Sira LB (2007) NeuroImage 37:40–47.

(One of) The gene for PPI discovered

Prepulse inhibition is an enduring phenotype of schizophrenia. In simple words, PPI is the diminished startle response exhibited by an organism, when a weaker stimulus precedes a stronger, normally-startle-response-producing stimulus. It is believed that PPI deficits result from the sensorimotor gating deficits present in Schizophrenia probands. the graphic below shows how the normal prepulse inhibition works. In schizophrenia, this doesn’t quite work and the startle response does not diminish with a prepulse being present.

A recent study by Akiko et al in PLOS biology has found a gene that , when knocked out in mice, led to PPI deficits akin to that seen in Schizophrenia. They also used Quantitative Trait Loci method to find the gene associated with PPI and found FABP7 to fit the bill. I present here, the abstract, author’s summary and conclusion.

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL’s proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming.

A startle response to an unexpected, strong startling stimulus can be suppressed by an immediately preceding low-intensity stimulus, thereby eliciting little behavioral response. This phenomenon, called prepulse inhibition (PPI), has been observed in all mammals tested and is thought to reflect sensory-motor gating functions in organisms. PPI is diminished in human schizophrenia, raising the possibility that PPI might serve as a potential biological marker for the disease. Once the genes regulating PPI in lower animals are identified, it is expected that the human orthologs will be strong candidate genes for schizophrenia. In this study, we first performed a genetic dissection of mouse PPI using quantitative trait loci analysis, which detects chromosomal regions harboring causative genes. Further analyses including those of knockout mice, allowed us to identify one potential causative gene, Fabp7 (fatty acid binding protein 7, brain), a chaperon for the essential fatty acid docosahexaenoic acid. Human studies showed that the FABP7 gene is modestly associated with schizophrenia and that transcript expression levels are up-regulated in schizophrenic brains. From these results, we propose that a FABP7 protein-mediated disturbance of essential lipid metabolism in developing brains may be one risk factor in the development of schizophrenia, with a greater effect in males.

The evidence accumulated in this study consistently supports causation by Fabp7 as the sole gene or one of the multiple genetic substrates underlying the Chromosome-10 QTL of PPI. The gene’s effects may be exerted through differential regulation of transcript levels in B6 and C3 mice at a critical period. Importantly, the FABP7 gene, which is modestly associated with schizophrenia in the current study, has the potential to link together the three compelling etiological hypotheses of schizophrenia, namely the NMDA, developmental, and glial (astrocyte) theories . The gene appears to make a larger contribution to PPI and schizophrenia in males. The remaining newly identified but uncharacterized QTLs in this study should provide a valuable resource for continuing molecular studies into PPI and schizophrenia mechanisms. Finally, there are no established prophylactic interventions for schizophrenia. Our results raise the possibility of cohort studies to examine whether replenishment of DHA in pregnant mothers can be beneficial in reducing the chance of schizophrenia development in their offspring, especially for high-risk families. Such analyses should preferably take into account genotypes that affect function and expression of FABP7 via both direct and indirect mechanisms.

I am excited by this research. The endophenotype-leading-to-genotype sort of research is very promising in that it treats complex disorders like schizophrenia one small step at a time and by identifying genes that may be underlying the schizophrenic condition, give us insights into the mechanisms involved. Anyway, I myself strongly believe that sensory gating theory of schizophrenia is on the right track and studies like these can only lead us closer to solving the mystery. One particular thing to note is that FABP7 has differential sex effects with its effects being more prominent in males and this too fits nicely with the fact that schizophrenia is more common in males and occurs at earlier age.

cortex maturation: lag, span and thickness: ADHD, Schizophrenia, autism , IQ

There is an article making waves regarding the delayed maturation of the cortex of children with ADHD and so I thought I will throw in my two cents and try to simplify things.

First what is cortex maturation- the cortex of normal children first increases in size (as presumably new connections are made) , reaches a peak around 8 years of age and then the cortex thins (as spurious connections are pruned). We normally think of more connections being more beneficial, so it stands to reason why pruning should happen- but more connections do not translate into better connections- we only need to retain the right connections – the spurious connections need to be mercilessly pruned, if we are to function correctly. A theory based on this logic also asserts that we are born synaesthetes, but the spurious connections get pruned under normal development.

Now there are several things that can go wrong with this wiring and pruning process. Too much wiring can leave you with a thicker than normal cortex , too much pruning can leave you with lesser connections than required for normal functioning. Also the achievement of normal thickness, and subsequent thinnness can be developmentally shifted or lag from the normal developmental plan. Finally the thickening and thinnening may be squeezed in time and may happen at a faster rate for some individuals. Conversely, this may be spread over a broader time period and o9ccur at a relatively slower rate for other individuals. Considering the three factors of Size ( peak thichkness/ thinnness achieved), Lag (start and end of thickening and thinning process) and Rate (faster development over small time frame or longer span with slow rate of pruning/ initial connection formation) one gets 6 combinations (if we treat them as independent of each other) . Also considering that Thickening (initial connection formation) and Thinning (subsequent pruning) may also be independent one gets 12 combinations. these are sufficiently complex for me to abstain from making any sweeping generalizations. So I’ll go to data:
1. In ADHD, new research (as also highlighted above) reveals, that the development (thickening and thinning ) of cortex is similar to normal individuals- only it is slightly shifted and starts later. this explains why ADHD disappears after teenage and is a problem only in childhood.

2. Children with higher IQ have faster rate of thickening and thinning of cortex as seen from graphic below.

3. Research from Paul Thomsaon’s lab at UCLA has shown that in schizophrenia the normal pruning process does not stop in teenage as in normal adults, but continues beyond the early teenage resulting in more pruning than is normal.
4. I’ve read claims that in Autism the cortex is thicker and that it matures early. I’m tempted to posit Autism as a reverse trend of schizophrenic maturation, but need more accurate refernces and would be highly obliged if someone points me to appropriate resources.

All this seems very promising and I would be watching ne23s related to these developments more closely in future , considering that some of these are comorbid – like autism and IQ in high functioning ASDers and Creativity and Schizophrenia.

Schizophrenia: sensory gating and extracting meaning from noise

I have blogged extensively in the past regarding schizophrenia and how people that are on that end of the cognitive thinking style are marked by a propensity to abstract meaning from apparent noise and meaningless or coincidental events. This, I have contrasted with Autistic thinking style which does not endow meaning even where it is legitimate.

It is also well known that Schizophrenics have a deficit with sensory gating and thus have loose attention/ loose associations etc. and are generally marked by less focal attention. This may lead to lowered filtering of irrelevant stimuli, which may lead to unusual experiences.

It is my contention that these two aspects may be independent of each other and when they come together may lead to psychosis. The deficits in sensory gating give rise to unusual experiences, while the normal confabulating left-brain mechanisms would try to explain the unusual experiences or noise in terms of a coherent narrative. If the first propensity to endow more meaning to even meaningless stimuli gets conjuncted with sensory gating, one may strew together a narrative that is not in touch with reality and thus lead to full blown psychosis, including delusions and hallucinations.

A recent study has just demonstrated that Schizophrenics have a propensity to derive meaning out of what is auditory noise for other normal people. I think there are two issues involved here- first more words were extracted from the auditory noise signal by the schizophrenics, and second they gave meaning to those words by strewing them together as ‘phrases’. The length of the phrases heard for prodormant schizophrenics, indicated whether they were likely to suffer from schizophrenia in the future, if not on medication. thus both sensory gating deficits and meaning-endowing deficits seem to be at work.

A tendency to extract messages from meaningless noise could be an early sign of schizophrenia, according to a study by Yale School of Medicine researchers.

The study this month in the British Journal of Psychiatry reported on 43 participants diagnosed with “prodromal symptoms”- meaning they exhibited early warning signs of psychosis such as social withdrawal, mild perceptual alterations, or misinterpretation of social cues.

Participants in the study were randomly assigned to take the anti-psychotic medication olanzapine or a placebo, and then symptoms and neuropsychological function were assessed for up to two years.

During the “babble task,” participants listened with headphones to overlapping recordings of six speakers reading neutral texts, which made the words virtually incomprehensible. The participants were asked to repeat any words or phrases that they heard. Only four words-“increase,” “children,” “A-OK,” and “Republican”-were consistently reproduced.

Eighty percent of the participants who “heard” phrases of four or more words in length went on to develop a schizophrenia-related illness during times that they were not taking olanzapine, said the lead author, Ralph Hoffman, M.D., associate professor of psychiatry. In contrast, only six percent of those in the study converted to schizophrenia-related illness if the phrases “heard” were less than three words in length.

“A tendency to extract message-like meaning from meaningless sensory information can, over time, produce a ‘matrix of unreality’ that triggers the initial psychotic phase of schizophrenia-spectrum disorders,” Hoffman said.

To me, this is further support for my hypothesis that Schizophrenic thinking style is marked by extracting too much meaning and it also supports the popular attention-arousal model of schizophrenia that considers the sensory gating deficits leading to hyperarousal and that in turn leading to loose and defocussed attention and this feeding on itself in a downward spiral. you can learn more about the theory by watching this excellent video.

Note related, though relevant to schizophrenia, is a new study that finds that Schizophrenics are more ‘theoretically ‘ rational as compared to normal people.

Schizophrenia fact sheet

This is just an FYI post regarding a great Schizophrenia fact sheet that is available on the net. do have a look and provide more facts as to what we know and what we do not know about this illness.