Schizotype

[monotonic]

That's interesting. I've had the experience of the game not stopping when I turned it off, but I never thought this was normal. I always associated this with extreme mental stimulation and never had the idea that it may be healthy. If anything it was distracting to me and I wanted it to stop. One example is the N-back game that got so popular for its cognitive enhancement benefits.

"Games" make it easy to reach this state (of course, like a mouse in a maze). It is not so simple to find real-life situations that give the same potential for high mental stimulation, but those situations would undoubtedly be much more growth-inducing.

 

[Psalehesost]

I had been pondering whether schizophrenia was really a part of the autistic spectrum of disorders or vice versa when I first looked into autism in a serious way, but recently I haven't been able to acquire the info that could have shed a light on that idea one way or the other.

I looked into this a bit, because I was curious about cognitive slippage and autistic spectrum conditions; I've had plenty of what I think is cognitive slippage associated with vague "intuition", and have an Asperger diagnosis. The "intuition" appears in decision-making and in considering the attributes of things. I will address this issue in the second part of this post. First, the information I have found:

In this paper (freely accessible), a comparison is made between genetic factors associated with autism and with schizophrenia. They mention four hypotheses - (a) autism is a subset of schizophrenia; (b) they are genetically separate; (c) they are diametric opposites; (d) they partially overlap.

These hypotheses are narrowed down to two, that they partially overlap or, what they conclude is the most likely, that they are diametrically opposed: (My bolding.)

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

They seem to be opposed in terms of brain development and structure, and among genes examined, four also contrast. (Duplication in two is associated with autism, whereas deletion is associated with schizophrenia; and two present the other way around.) But there are also 20 genes that overlap. In addition, whereas 2 genes have positive association with autism but not schizophrenia, 11 have positive association with schizophrenia but not autism.

When it comes to schizotaxia, I guess it's an open question whether the gene or genes responsible for that are among the ones which are opposite, the ones which otherwise differ, or the ones which overlap. And if it would be shared, what effects the differing genes have on compensation/decompensation.

Drawing upon a wider range of searching and reading, there is great individual variation in cognitive strengths and weaknesses in people on the autistic spectrum. The same also goes for idiosyncracies of thought, from obsessive-compulsive traits, to the degree of preoccupation with imagination, to disordered thought including cognitive slippage. There are also some cases of delusion, be they persecutory, grandiose, incolving hallucinations, etc.

It's been proposed that, at least in persecutory delusions, different mechanisms are at play in comparison to schizophrenics: Lack of social understanding combined with having had experiences of hostility, and tending to think of others in relation to the self and one's experiences, causes misattribution of motives and leads to forming a faulty belief system.

More generally, in part it's an open question what causes such problems in some on the autistic spectrum. Even where delusions are present, core characteristics unique to the autistic spectrum remain, both without and following successful treatment for delusions. Genetic factors might be at play; perhaps a person having the genes for the autistic spectrum, along with some selection of the otherwise non-overlapping genes for the schizo-spectrum, makes for manifesting additional schizo-features. And/or, other things may be involved. In any case, some kinds of cognitive slippage, and even more generally, highly idiosyncratic thinking, seem very common, while clinical issues of delusion are very rare.

Now I come to some speculation: To varying extents, people on the autistic spectrum can, as measured by tests, tend to underincorporate stimuli in their cognitive processing. Detail-oriented cognitive processing can also be unusually strong, while missing the "bigger picture" and having poorer comprehension. Then there are the various sensory processing issues - hypersensitivity (sometimes mixed in peculiar ways with hyposensitivity) - and, seemingly, some degree of lack of integration of sensory inputs. Could this relate to the opposite of what the schizotaxic nervous system does - instead of discrimination being inadequate, could it be excessive?

It is known (cited in the gene study at the beginning) that connectivity between different brain areas tends to be poorer than in the average brain in those on the autistic spectrum - more gray tissue, less white; greater tendency towards local processing at the cost of global. There is also, due to genetic factors, an "imbalance towards excitatory glutamatergic cortical neurotransmission." Together with excessive discrimination, if that is the case, could scattered, locally limited information together with ramped-up local processing cause cognitive errors, including some kinds of cognitive slippage, albeit on a wholly different basis?

I'll finish this part by noting my personal - introspective - experience: I've experienced that, on the one hand, I seem to have a sharp, outer "edge" to the intellect - an ability to focus on, follow and process details accurately whether or not I actually understand anything. And, on the other hand, a particularly fuzzy and sweeping intuition. (The result of information linked across the brain being somewhat limited, "coarse-grained", details not being as integrated?) But I seem to lack in what is in-between these two extremes - the processing which I think is generally the basis of insight.

This lack has become clearer over time. Only some years ago, I think it was big enough that there was no possibility of seeing it. In 2010, I had begun to "feel" it, but without understanding it - why it felt like I had no "grasp" on things, including life and all the bigger things to be understood therein in order to have a direction. That has gradually changed - at first such that I developed a poor grasp rather than having none, rather than simply following the current of life - then, now hopefully such that I have a somewhat better grasp and, in setting a direction, do not merely spin around without a clue. On a smaller scale, other changes have also been noticed in this latest stage of change, such as becoming able to understand some things I couldn't before - e.g. some mathematics, where previously all I had were the vaguest ideas and the formulas. And - becoming more self-critical.


Now for the second part, and addressing the cognitive slippage I think I've seen in myself - the problem of the vague "intuition" mentioned at the very beginning. ('The "intuition" appears in decision-making and in considering the attributes of things.' The distinction between the fuzzy intuition mentioned last in the previous section and this, is that this is a particular kind of it which interferes with thought and decision-making.)

In The Swamp, there is an old thread of mine dealing with sensations of "energy" and the judging of the same, which is very much related. It is only a matter of whether there is an explicit labeling of what it is (a private explanation, as I then had in "energy"), or if the "intuition" persists regardless, as it has done even when questioning such old beliefs. (Only, in questioning, it has somewhat lessened in frequency and intensity.)

Basically, what it does is make some things (ideas, plans, possible actions) feel "right" and some feel "wrong". When submerged in such "intuition", there is a lack of critical-mindedness. There is often mild positive or negative feeling connected to these inner sensations, which is what makes them motivating - either pulling me towards, or away from, something. Occasionally, such feeling may be stronger. It may also be absent.

In this recent post, I wrote about an ongoing struggle with all too often not really thinking and instead being pulled around by System 1 impulses. It quotes an earlier post, which makes reference to mental sensations. Together, these posts describe the present state of the struggle with "intuition" and uncritically being influenced by it.

I should add that in the confused thinking that can arise when submerged in this "intuition", all five of Meehl's criteria for cognitive slippage that obyvatel quoted can be fulfilled:

1) Content of construction or hypotheses intrinsically improbable.

2) Systematic failure to consider alternative hypothesis of higher antecedent probability which would explain the same allegedly “corroborating” facts.

3) Confusion between “observation” and “immediate inference” in the verbal description of an allegedly corroborating fact (e.g., patient persistently fails to consider that his perceptions of other people’s thoughts, motives or affects are, strictly speaking, not observations but inferences).

4) Handling of discorroborative data by subsuming them under multiple alternative and ad hoc hypotheses, instead of re-examining the main one.

5) At the time, definite belief, as contrasted with admittedly unreasonable, obsessional concern or preoccupation.

In this case, the automatic "conclusions" of the "intuition" are very often confused for observations. Also, for a very long time the validity of such "intuition" was an unquestioned belief; instances that could be interpreted as supporting it were used to do so, while instances that suggested it might be bunk were explained away by putting them in new, ad-hoc hypotheses. In the moment, while submerged in such "thinking", they were also the only thing considered, and as such believed in.

Being submerged in such "intuition" can further involve conflicting impulses, and as System 2 is meanwhile effectively disabled, the result is then a blank, indecisive mind, vacillating between different "intuitions". Given the sheer regularity of these instances in the past, the only difference from the following description is that the "intuitions" (while in themselves generally vague and unclear) are generally connected to something concrete, which they "represent":

Another example of cognitive slippage [...] getting perplexed and confused and mixed up in his thinking with such a high frequency that it represents a major feature of their personality. This type of confusion does not refer to being conflicted between different options which can be clearly articulated. Cognitive slippage applies when the thoughts and ideas are separately vague, scrambled or unclear. Thought deprivation or the mind going blank quite often would indicate cognitive slippage.

Fortunately, there is change regarding these things. While such "intuition" still occurs regularly, "thinking" built on top of it is now regularly questioned, and when the mind stops in the midst of a conflict of such impulses, questioning it all and breaking out of it restores thought, which can then lead to decisions. The remaining attraction to this "intuition" - what makes it come on so easily unless I focus on ignoring it and applying rational thought - is, I think, that it is both generally mildly pleasant and effortless, which has made it an ingrained automatic habit in the time since it appeared in my late teens. It can also vary widely in the level of intensity and involvement - it can be a more subtle presence in the background of the mind, and either remain so during an activity, or intensify and steal more focus. Intensity seems, on average, to more recently have weakened, though great variation remains.

 

[monotonic]

Psalehesost, your "intuition" sounds exactly like what I describe in the "music as a narrative" thread. After becoming able to remember those periods of thought however they don't seem so mysterious to me anymore. Years ago I would have called it intuition, but I have almost forgotten that the word applies, because I always associated "intuition" with the mysterious. The phenomenon doesn't seem mysterious to me anymore at this point, and seems rather mechanical, just another layer of thought. I also wonder however if the intuitions I'm working with were formed years ago and have now crystallized into predictable thought patterns, and that I simply haven't learned anything new fast enough to experience the mysterious, vague kind of intuition as of late.

But, if cognitive slippage is associated with schizophrenia, and we're both diagnosed autistic (I'm aspergers supposedly) yet have experienced slippage, then what does diametrically opposed really mean? I don't really have the background to understand all this well...

Your connection with intuition passing into slippage is really interesting. It describes the things I've said about my thinking, but more concisely. It seems to have to do with attention; intuitive "immersion" like you say has a strange tendency to lead to into a mental sleep-like state, where the mind keeps going and the original aim is lost. To me, dreams have very much the same feeling as intuitive immersion. At the same time, I've experienced going into a dream-like state, losing outward vision, while sitting at my computer and concentrating very hard on a problem I want to solve with newly acquired understanding. When this first started happening my mind would usually just go blank, because the experience was just so hard to follow in a way conducive to memory. Thus 1: I would have a conclusion without remembering how I came to it, 2: I would lose awareness/attention and I would come back with no answer and having even forgotten the original problem, 3: I would start dreaming and catch myself, or 4: I would realize I needed to breathe or was falling off my chair and then lose the intuitive flow. After getting better, and learning what I described as "interrogating" in the aforementioned thread, I became more able to hold this state and control it, and to tolerate disruptions.

I think we might define the "slippage threshold". I think that bad diet and many other things lower the slippage point, and for some people it gets quite low.

And still there are moments when Intuition seems to be on rocket rails, working quickly and flawlessly to the letter. These periods are very rare in me, and tend to last only a few hours. And then it's a year or so until it happens again. It was much more often when I was young, and I suspect it is highly influenced by learning patterns and whether you ARE learning. It happened to me once while I was practicing 4th way self-awareness techniques while reading.

On a related note, I find this music calms me in a way conducive to intuitive flow.

https://www.youtube.com/watch?v=okz61xnCFJE&list=PLMPMu3oJ9repPsv9OyXQInNV2cEJMkVDl

 

[obyvatel]

Psalehesost, thanks for the paper comparing autistic spectrum and schizophrenia. The statement that autism is related to dysregulated overdevelopment of the social brain while schizophrenia is related to underdevelopment of the social brain was interesting. Other studies have reported that brain circuits related to social behavior are active but out of sync with other related areas in autism spectrum disorders. Sensory overload is also reported to be a component of the autism spectrum. We can contrast and compare these factors with Meehl's hypothesis about the cause of schizotypy - fundamental integrative defect of hypokrisia. While the autistic world is dysregulated, it is perhaps far "richer" in terms of content than the world of the schizotype.

I would speculate here that the distorted world view and the pessimistic outlook about human potential that characterizes the majority of the so-called intellectual circles is influenced by schizotypal thinking. It wouldn't be a surprise if a significant number of "intellectual stalwarts" are later revealed to be carriers of schizotypy. Freud, Maslow, Marx, Dawkins, Ayn Rand as well as many others of the same ilk would perhaps fall into this category. The founders and proponents of many religious cults would perhaps join the club as well. The role played by such people in the ideological arena clears the way for the more predatory essential psychopaths to establish their stranglehold on human society - like Lobaczewski discussed in Ponerology. The scale at which this takes place may however be larger than what he expected.

If the above is not too far off base, then it becomes very important to clearly distinguish between schizotypy and other disorders which have some surface commonality in terms of external manifestations but are very different in their essential nature. And perhaps that is why the waters are quite deliberately muddied in this respect so that it is very difficult to discern the differences.

Cognitive distortion or disordered thought can arise out of a number of different causes. Lack of proper knowledge and training in what Gurdjieff would call "objective reason" - which is universal in a certain sense due to the ponerized environment in which we all grow up - would play a big role as would the emotionally toxic effects of the environment which leads to emotional repression and formation of neurotic defense mechanisms . Unhealthy diet leading to chemical imbalances and exacerbating vulnerabilities due to a variety of inherited conditions of a different nature than schizotypy would be another big one. So it is best not to equate cognitive distortion with schizotypy. Also, schizotypy is not very likely to be self-diagnosable due to its very nature. So, it is best to not spend any energy on thoughts like "am I a schizotype" and focus the efforts on identifying cognitive distortions and eliminating them.

 

[H-KQGE]

Hello Psalehesost & thank you for the information you provided, as well as your energy in the posts from your links. I read them when you first posted but I was reluctant to reply for a few reasons, one being a run of poor health from over over a month or so. There's also my usual self-doubt about what I actually know (always under review) & what I am feeling at any time. I always take great interest when people post things that are difficult to grasp in general; not just technical information that I have little or no experience of, but emotions & thoughts especially. I just want to say a bit based on reading some of your posts, (from your links) these I related to & I felt I should assess myself over a short while; to see if my feelings & thoughts were similar to those the first time around.

Reading how some people's thoughts are formulated normally gets me reflecting on my own, regularly now, with the strong information on similar threads to this where neuroanatomy & neurobiology are concerned. With so much to take in from various disciplines ( & I have no background in any of these, just deep interest) I have to periodically slow down, take a breather, which is why I didn't add to what I had found around the time of my post which you quoted. There was a fair bit of valuable information which I had seen but illness, information overload & living with relatives that are highly pathological, got the better of me.

Where thoughts are concerned I have had to really delve into how I process them, this is only in the last few years of finding Laura's work & the Cass site. I will describe the process as simply as I can. I will read something here for example, & this will trigger thoughts in that direction. Whether it's interesting or not doesn't seem to really matter, it's the ideas that arrive that is the point. Upon arrival (after analysing this a lot) they come as what I can only describe as "packets", something I just assumed that everyone else receives in a similar way.
Then most times I will have an impression of that "packet" (if any of this isn't clear I will suggest a mental picture, in this case anything in packaging like cereal boxes or whatever will do) based on what I had read, & a feeling of comprehension will arise that is tempting to stay with rather than to "open" or investigate. When "opened" I find many more ideas leading off elsewhere ( so for this "packet" example the smaller/other ideas are the "contents") & this is where the trouble begins. I'm assuming that my mind goes into autopilot, & coupled with natural curiosity, I follow those tangents. This is when reading things that aren't terribly interesting, mind. When I am interested ( & have a good understanding) & come across something that piques it, I get a wave or rush of these "packets".

Being aware of this on & off over the last few years with lots of writing exercises & now with the recommended reading material, I have confirmed this pattern & it's problematic for writing. Decision-making ("should I post this? Nah, someone more knowledgeable will have the info & do a better job anyway." These thoughts are frequent) is only hampered by self-doubt & caution.

These "packets" where knowledge/understanding were already there, (as the base) can be recognized in my mind similar to recognizing say, a box of "frosted lucky charms" cereal. I know what it is I understand the marketing ploy, I know that they're not "magically delicious", nor are they good for you. I've taken in most of the info associated with it but I still need to open the box to see if it is what I think or have assumed it is.
In the past I would think of this as intuition & with non-complex information I could get away with it simply because of the knowledge base & some valid assumptions. Not so with complex things, these require all your faculties, but with what is now to me "racing thoughts" (often they race ahead of what's being read or even watched on-screen, or listened to like SOTT radio show) & not intuition, I'm wondering what damage I've not only inherited; but what i've acquired from a pathological family.

It really is a case of half & half between whether I will go with a feeling of understanding something, (knowledge base present, intricacies of new information not - partially glossed over when topic isn't difficult) or going with "opening the packet" & investigating the thoughts/ideas that will invariably follow - leading to more "packets". Which is tiring. There's more to that but basically, that's how my thought process usually goes, though physical daily interactions with people doesn't bring that about.

These hypotheses are narrowed down to two, that they partially overlap or, what they conclude is the most likely, that they are diametrically opposed […] They seem to be opposed in terms of brain development and structure, and among genes examined, four also contrast. (Duplication in two is associated with autism, whereas deletion is associated with schizophrenia; and two present the other way around.) But there are also 20 genes that overlap. In addition, whereas 2 genes have positive association with autism but not schizophrenia, 11 have positive association with schizophrenia but not autism.

When it comes to schizotaxia, I guess it's an open question whether the gene or genes responsible for that are among the ones which are opposite, the ones which otherwise differ, or the ones which overlap. And if it would be shared, what effects the differing genes have on compensation/decompensation.

When I first read PP I had the feeling about schizophrenia (two years ago) being possibly part of something larger, this stemmed from that C's session containing info about shamans. Probably the most intriguing part of that session, once I had had the feeling about schizophrenia as part of something larger, was part of the answer: "genetics associated with schizophrenia can be either a doorway or a barrier. Second, the manifestation of schizophrenia can take non-ordinary pathways. That is to say that diet can activate the pathway without the concomitant benefits.[…]Primitive societies that eat according to the normal diet for human beings do not have "schizophrenics", but they do have shamans who can "see"."

The first bolded part set that feeling (leading to the idea more recently) off - "associated with" - then the fact that the word schizophrenics was used with quotes. Anyway, the autism angle came to me from another thread & the fact that my mother, as the eldest of four sisters, is schizophrenic & my youngest aunt being the first to deteriorate over 20 years ago, is in "better" mental health than her; the autism symptoms (some) seemed to fit her. So I wrote what I did which you quoted. So what I wrote near the start of this post about my thought process (feeling of knowing/"intuitions" formerly, versus investigating individual thoughts/"opening the packet") is actually how I arrived at thoughts of autism & schizophrenia. After reading up on autistic spectrum disorders I had the first part of my thought process kick in (feeling of knowing) which meant that I leant toward option b, (genetically separate) & option d. (partial overlap) I still think that there's more to it though.

Finally...

Drawing upon a wider range of searching and reading, there is great individual variation in cognitive strengths and weaknesses in people on the autistic spectrum. The same also goes for idiosyncracies of thought, from obsessive-compulsive traits, to the degree of preoccupation with imagination, to disordered thought including cognitive slippage. There are also some cases of delusion, be they persecutory, grandiose, incolving hallucinations, etc.

It's been proposed that, at least in persecutory delusions, different mechanisms are at play in comparison to schizophrenics: Lack of social understanding combined with having had experiences of hostility, and tending to think of others in relation to the self and one's experiences, causes misattribution of motives and leads to forming a faulty belief system.

More generally, in part it's an open question what causes such problems in some on the autistic spectrum. Even where delusions are present, core characteristics unique to the autistic spectrum remain, both without and following successful treatment for delusions. Genetic factors might be at play; perhaps a person having the genes for the autistic spectrum, along with some selection of the otherwise non-overlapping genes for the schizo-spectrum, makes for manifesting additional schizo-features. And/or, other things may be involved. In any case, some kinds of cognitive slippage, and even more generally, highly idiosyncratic thinking, seem very common, while clinical issues of delusion are very rare.

All of that is what I've seen in my own limited research (didn't post as I didn't know how to talk about them in a meaningful way, IOW non-rambling) & the bolded parts reminds me of thoughts I had about geniuses, "geeks", "nerds" & whatever else they call these groups of people. I had seen an array of articles in SOTT & some on the forum (I think so, it would've been over a year ago) & elsewhere incorporating the usual, diet & lifestyle, epigenetics & environment etc. The thoughts of this group(s) of people kept returning, the skin problems, the food intolerances (usually lactose) hyperhydrosis, respiratory stuff & more. Then the more I heard about the brains & intellect of these types, the more I thought about the line between genius & "madness" (whatever that phrase is) the lack of social integration, but not necessarily delusions for school "geeks" & the others (your second paragraph bolded) because as far as I know they're always persecuted. Persecutory delusions would apply to some famous "geeks" & boffins in history that have been documented I think. The rich ones & influentials.

The high-end cognitive processing of those on the autistic spectrum (the ones that do better) where they can zero in on details to a great degree, makes me think that "geeks" & "nerds"/"boffins" (& how many adults are "geeky" or "a bit of a nerd?") have these genes, one or the other (schizophrenia/autism) overlapping with the specific brain structure in place & environmental handicaps moving in unison, or out of sync/fluctuating especially if there's an overlap of autism & schizophrenia. Genes getting activated & others suppressed while portions of the brain get scrambled I think.

But again thanks for the info & the links, they seem to have re-energized me for these subjects.

 

[Laura]

Since part of what we are looking at here appears to be a "slippage" in cognitive/synaptic functioning, I was curious when I saw the following article yesterday as to whether what it is describing as "information flow" could be helpful in understanding this.

The key to consciousness: Efficient information flow?

Tia Ghose
LiveScience
Thu, 24 Oct 2013

The moment a person slips from conscious thought into unconsciousness has long been a mystery.

Now researchers have pinpointed exactly what goes on in the brain as people become unconscious after taking anesthesia. It turns out that there probably aren't individual neurons, or brain cells, responsible for consciousness.

"This data shows that consciousness might not be the result of a special group of neurons, but rather might be the result of how neurons communicate with one another," study co-author Martin Monti, a psychology professor at the University of California at Los Angeles, wrote in an email.

When people are conscious, information zips from one place to another along a direct route, much like an express bus, whereas the way information travels in the unconscious brain is more like taking several buses and stopping in North Dakota and Tennessee to get from New York to Los Angeles, Monti said.

Mystery of consciousness

To study consciousness in more depth, Monti and his colleagues used functional magnetic resonance imaging (fMRI) to scan the brains of 12 healthy people ages 18 to 31 while they were given the anesthetic propofol.

As the participants lost consciousness, the fMRI scans showed a change in blood flow patterns across the brain. That brain activity suggested the flow of information in their brains became much more inefficient.

"If you imagine being a bit of information that has to travel from, say, occipital cortex -- at the back of your brain -- to prefrontal cortex -- at the front end of your brain -- you might either get there efficiently, which is to say via only a few synapses, or inefficiently, via several more synapses," Monti said. "When we lose consciousness due to propofol, it appears that suddenly the travel of information becomes more inefficient and less direct."

Many unknowns

The scientists didn't follow the people throughout a long period of sedation, they don't know whether this inefficient information flow persists throughout unconsciousness or just when people first lose consciousness

In fact, other studies of people during sleep show that consciousness seems to be connected to more efficient brain processing, Monti said.

It's also not clear yet whether anesthesia-induced unconsciousness mirrors the state experienced by people who are in a coma or have a severe brain injury.

"In healthy volunteers, what changes is only the way in which information flows within the brain networks," Monti said. "In patients, the network itself has also been severely compromised due to the injury, so in that circumstance, there might be multiple mechanisms at play."

Efficient, organized brain processes are not enough on their own to create a state of consciousness. For instance, many behaviors, such as driving a stick shift, or coordinating the movements of walking, are done without conscious thought. And even patients in a vegetative state have some organized brain function, Monti said.

Ultimately, the team hopes a deeper understanding of the nature of consciousness could help reignite consciousness in patients who have lost it.

The findings were detailed online Oct. 17 in the journal PLOS Computational Biology.

 

[mkrnhr]

FWIW, the original paper is freely accessible here: _http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003271

 

[SeekinTruth]

Since part of what we are looking at here appears to be a "slippage" in cognitive/synaptic functioning, I was curious when I saw the following article yesterday as to whether what it is describing as "information flow" could be helpful in understanding this.

The key to consciousness: Efficient information flow?

Tia Ghose
LiveScience
Thu, 24 Oct 2013

The moment a person slips from conscious thought into unconsciousness has long been a mystery.

Now researchers have pinpointed exactly what goes on in the brain as people become unconscious after taking anesthesia. It turns out that there probably aren't individual neurons, or brain cells, responsible for consciousness.

"This data shows that consciousness might not be the result of a special group of neurons, but rather might be the result of how neurons communicate with one another," study co-author Martin Monti, a psychology professor at the University of California at Los Angeles, wrote in an email.

When people are conscious, information zips from one place to another along a direct route, much like an express bus, whereas the way information travels in the unconscious brain is more like taking several buses and stopping in North Dakota and Tennessee to get from New York to Los Angeles, Monti said.

Mystery of consciousness

To study consciousness in more depth, Monti and his colleagues used functional magnetic resonance imaging (fMRI) to scan the brains of 12 healthy people ages 18 to 31 while they were given the anesthetic propofol.

As the participants lost consciousness, the fMRI scans showed a change in blood flow patterns across the brain. That brain activity suggested the flow of information in their brains became much more inefficient.

"If you imagine being a bit of information that has to travel from, say, occipital cortex -- at the back of your brain -- to prefrontal cortex -- at the front end of your brain -- you might either get there efficiently, which is to say via only a few synapses, or inefficiently, via several more synapses," Monti said. "When we lose consciousness due to propofol, it appears that suddenly the travel of information becomes more inefficient and less direct."

Many unknowns

The scientists didn't follow the people throughout a long period of sedation, they don't know whether this inefficient information flow persists throughout unconsciousness or just when people first lose consciousness

In fact, other studies of people during sleep show that consciousness seems to be connected to more efficient brain processing, Monti said.

It's also not clear yet whether anesthesia-induced unconsciousness mirrors the state experienced by people who are in a coma or have a severe brain injury.

"In healthy volunteers, what changes is only the way in which information flows within the brain networks," Monti said. "In patients, the network itself has also been severely compromised due to the injury, so in that circumstance, there might be multiple mechanisms at play."

Efficient, organized brain processes are not enough on their own to create a state of consciousness. For instance, many behaviors, such as driving a stick shift, or coordinating the movements of walking, are done without conscious thought. And even patients in a vegetative state have some organized brain function, Monti said.

Ultimately, the team hopes a deeper understanding of the nature of consciousness could help reignite consciousness in patients who have lost it.

The findings were detailed online Oct. 17 in the journal PLOS Computational Biology.

Those are very interesting findings. Even beyond this topic, it seems to provide even more evidence that consciousness isn't some "byproduct" of the brain's processes but is above and beyond the physical brain. Like Sheldrake has made the point: consciousness is like the radio or television waves/signals and the box in your house (brain) is just a receiver. When the box malfunctions, there will be problems, but it's with the physical device and its ability to receive the information.

 

[Gaby]

Those are very interesting findings. Even beyond this topic, it seems to provide even more evidence that consciousness isn't some "byproduct" of the brain's processes but is above and beyond the physical brain. Like Sheldrake has made the point: consciousness is like the radio or television waves/signals and the box in your house (brain) is just a receiver. When the box malfunctions, there will be problems, but it's with the physical device and its ability to receive the information.

It is also interesting to note that one of the main keys of the breathing program in EE, is to achieve a more efficient flow of information in the brain. There is more information exchange between the two hemispheres of the brain (left-right integration), which means there is increased coherence and better problem-solving. It also improves balance between parts of the cortex and subcortex which means that higher functions of the cortex can influence primitive influences from the subcortex. There is a synchronization between the input from the body, the thalamus, limbic system and cortex.

Better processing and integration from higher cognitive functions in the brain is one of the goals of stimulating the smart vagus in the polyvagal theory.

 

[Gaby]

Better processing and integration from higher cognitive functions in the brain is one of the goals of stimulating the smart vagus in the polyvagal theory.

Which is an empathetic and pro-social system, I would add to the above.

Here are a couple of studies on schizophrenia which might give more clues as to the abnormalities:

Circular inferences in schizophrenia

_http://brain.oxfordjournals.org/content/136/11/3227.abstract.html?etoc

Oxford Journals
Medicine
Brain
Volume 136, Issue 11
Pp. 3227-3241.

A considerable number of recent experimental and computational studies suggest that subtle impairments of excitatory to inhibitory balance or regulation are involved in many neurological and psychiatric conditions. The current paper aims to relate, specifically and quantitatively, excitatory to inhibitory imbalance with psychotic symptoms in schizophrenia. Considering that the brain constructs hierarchical causal models of the external world, we show that the failure to maintain the excitatory to inhibitory balance results in hallucinations as well as in the formation and subsequent consolidation of delusional beliefs. Indeed, the consequence of excitatory to inhibitory imbalance in a hierarchical neural network is equated to a pathological form of causal inference called ‘circular belief propagation’. In circular belief propagation, bottom-up sensory information and top-down predictions are reverberated, i.e. prior beliefs are misinterpreted as sensory observations and vice versa. As a result, these predictions are counted multiple times. Circular inference explains the emergence of erroneous percepts, the patient’s overconfidence when facing probabilistic choices, the learning of ‘unshakable’ causal relationships between unrelated events and a paradoxical immunity to perceptual illusions, which are all known to be associated with schizophrenia.

Midbrain dopamine function in schizophrenia and depression

_http://brain.oxfordjournals.org/content/136/11/3242.abstract.html?etoc

Elevated in vivo markers of presynaptic striatal dopamine activity have been a consistent finding in schizophrenia, and include a large effect size elevation in dopamine synthesis capacity. However, it is not known if the dopaminergic dysfunction is limited to the striatal terminals of dopamine neurons, or is also evident in the dopamine neuron cell bodies, which mostly originate in the substantia nigra. The aim of our studies was therefore to determine whether dopamine synthesis capacity is altered in the substantia nigra of people with schizophrenia, and how this relates to symptoms. In a post-mortem study, a semi-quantitative analysis of tyrosine hydroxylase staining was conducted in nigral dopaminergic cells from post-mortem tissue from patients with schizophrenia (n = 12), major depressive disorder (n = 13) and matched control subjects (n = 13). In an in vivo imaging study, nigral and striatal dopaminergic function was measured in patients with schizophrenia (n = 29) and matched healthy control subjects (n = 29) using 18F-dihydroxyphenyl-l-alanine (18F-DOPA) positron emission tomography. In the post-mortem study we found that tyrosine hydroxylase staining was significantly increased in nigral dopaminergic neurons in schizophrenia compared with both control subjects (P < 0.001) and major depressive disorder (P < 0.001). There was no significant difference in tyrosine hydroxylase staining between control subjects and patients with major depressive disorder, indicating that the elevation in schizophrenia is not a non-specific indicator of psychiatric illness. In the in vivo imaging study we found that 18F-dihydroxyphenyl-l-alanine uptake was elevated in both the substantia nigra and in the striatum of patients with schizophrenia (effect sizes = 0.85, P = 0.003 and 1.14, P < 0.0001, respectively) and, in the voxel-based analysis, was elevated in the right nigra (P < 0.05 corrected for family wise-error). Furthermore, nigral 18F-dihydroxyphenyl-l-alanine uptake was positively related with the severity of symptoms (r = 0.39, P = 0.035) in patients. However, whereas nigral and striatal 18F-dihydroxyphenyl-l-alanine uptake were positively related in control subjects (r = 0.63, P < 0.001), this was not the case in patients (r = 0.30, P = 0.11). These findings indicate that elevated dopamine synthesis capacity is seen in the nigral origin of dopamine neurons as well as their striatal terminals in schizophrenia, and is linked to symptom severity in patients.

 

[Approaching Infinity]

Since part of what we are looking at here appears to be a "slippage" in cognitive/synaptic functioning, I was curious when I saw the following article yesterday as to whether what it is describing as "information flow" could be helpful in understanding this.

After following up on a reference in the Kellys' book, "Irreducible Mind", I got Uttal's "The New Phrenology." I have only just started it, but the book is a criticism of the idea that different brain regions can be identified with certain cognitive functions (oversimplifying way too much here!), as well as the technology and the interpretation of the data from that technology. Kelly brings up the idea that the brain is primarily a sensorimotor device. Modularity in the brain is typically sensory and motor levels, but in cortical regions, modularity is difficult to find (probably because it's not there). If the mind is somehow distinct from the brain, I think it helps to see the brain primarily as an information-transformer. The brain receives information from the body (and by extension, the world), as well as from the mind. If things go wrong on the body/brain, that will affect what information is presented to the mind (and vice versa), and how that information is interpreted.

 

[H-KQGE]

Adding somewhat to the recent above information but from 2011...

Autism and Schizophrenia

March 15, 2011 | Autism, Schizophrenia
By Yael Dvir, MD and Jean A. Frazier, MD
Linked Articles
Introduction: Schizophrenia Spectrum Disorders
Autism and Schizophrenia
Cognitive Rehabilitation in Schizophrenia
Early Antecedents and Detection of Schizophrenia

Autism and SchizophreniaEmerging study results suggest that there are both clinical and biological links between autism and schizophrenia. The question regarding whether there is phenotypic overlap or comorbidity between autism and schizophrenia dates back to 1943, when Kanner1 first used the term “autism” to describe egocentricity. The distinction between the two disorders remained unclear for nearly 30 years, until DSM-II included children with autism under the diagnostic umbrella of schizophrenia, childhood type. In 1971, Kolvin2 conducted seminal research that highlighted the distinction between autism and schizophrenia, which influenced the decision to include the disorders as 2 separate categories in DSM-III.

The patient’s age at the onset of symptoms and the clinical presentation distinguish autism from early-onset schizophrenia. Also, the disorders are treated differently.2,3 Schizophrenia is thought to develop at a chance rate in individuals with autism. It is noteworthy, however, that children who have childhood-onset schizophrenia (COS) show fairly high premorbid rates of early developmental abnormalities.2,4-7

This article highlights the biological and clinical links between autism and schizophrenia.

Childhood-onset schizophrenia

COS—the onset of psychosis before age 13 years—is considered a rare and severe form of schizophrenia. Systematic studies of COS show high rates of the disorder being either preceded by or comorbid with autistic spectrum disorders (ASD).7

The first to describe the severity and frequency of prepsychotic developmental disorders in COS was Kolvin,2 who noted deficits in communication, motor development, and social relatedness. These deficits were found in 28% to 55% of children with ASD, and these observations have been replicated in multiple studies.6-8

Retrospective studies of children with schizophrenia reveal delays in language acquisition and visual-motor coordination during early childhood before the onset of psychotic symptoms.9 Alaghband-Rad and colleagues10 reviewed the premorbid histories of children with COS and noted language delays and transient motor stereotypies (patterned repetitive movements, postures, and utterances). Their findings suggest early developmental abnormalities of the temporal and frontal lobes as evidenced by prepsychotic language difficulties; the early transient motor stereotypies indicate developmental abnormalities of the basal ganglia.

Shared clinical features

Although the disorders are distinct, they have shared clinical features. Social withdrawal, communication impairment, and poor eye contact seen in ASD are similar to the negative symptoms seen in youths with schizophrenia.11 When higher-functioning individuals with autism are stressed, they become highly anxious and at times may appear thought-disordered and paranoid, particularly when they are asked to shift set (such as being asked to change a topic of conversation or to stop an activity that they are engaged in and begin a new activity).12 A subset of children (28%) in the ongoing NIMH study of COS have been reported to have comorbid COS and ASD.7

A number of researchers use different terms to describe this complex mix of psychiatric comorbidity and developmental psychopathology. At the Yale Child Study Center, a subgroup of children with ASD was labeled as having multiplex developmental disorder.13,14 Researchers in the Netherlands used the term “multiple complex developmental disorders” (MCDD) to describe children who met criteria for ASD and also exhibited affect dysregulation and disordered thinking.15-18 Of significant interest are follow-up studies, which showed that psychosis developed by adulthood in 64% of children with MCDD.16

Similarly, a study by Sprong and colleagues19 that compared youths with MCDD with youths at risk for psychosis found that although the groups clearly had differing early developmental and treatment histories, there were no differences in schizotypal traits, disorganization, and general prodromal symptoms. In that study, 78% of the MCDD group met criteria for at-risk mental state. The authors concluded that children with MCDD are at high risk for psychosis later in life.



What is already known about autism and schizophrenia?

? Although autism has long been recognized as a separate diagnostic entity from schizophrenia, both disorders share clinical features. Childhood-onset schizophrenia (COS), considered a rare and severe form of schizophrenia, frequently presents with premorbid developmental abnormalities. This prepsychotic developmental disorder includes deficits in communication, social relatedness, and motor development, similar to those seen in autism spectrum disorders (ASD).



What new information does this article add?

? This article highlights the biological and clinical links between the two disorders, reviewing shared genetics, brain changes, and similarities and differences in clinical presentations.



What are the implications for psychiatric practice?

? Autism and schizophrenia may present as 2 separate disorders that need to be differentiated, or as comorbid conditions. It is important to remember that some individuals may have both COS and ASD, which has implications when designing appropriate biopsychosocial interventions. Adult psychiatrists may benefit from additional training in the diagnosis of ASD in adults, whereas child psychiatrists may benefit from increased comfort with identifying primary psychotic symptoms in autistic youth.

Case Vignette

George is a 14-year-old boy who first presented to Dr Frazier at age 8 with a diagnosis of ASD. The diagnosis had initially been made when George was 27 months old and had been reconfirmed by numerous well-regarded autism experts over the years. George had received the usual autism-specific services, and although he made gains, he continued to present with atypical behaviors. George was referred to Dr Frazier because of an increase in the intensity and frequency of unusual and disturbing preoccupations that often had a morbid theme. Those who worked with him had difficulty in getting him off of these disturbing topics.

George also had unusual behaviors and mood-regulation difficulties. When he first presented to the clinic, he was disinhibited, emotionally unstable, and talked at length about his “other world.” His thoughts were loosely connected and he spoke about the friends in his other world who were talking to him. Initially, these friends were humming to him or saying hello. Because of a history of at least 1 depressive episode and what appeared to be more of a chronic euphoric state with affective lability, George was given a provisional comorbid diagnosis of bipolar disorder with psychotic features. Over the ensuing years, despite a number of medication trials including atypical antipsychotics and mood stabilizers, he became tortured by more persistent auditory hallucinations. “She” was particularly disturbing to him and he wanted her to go away.

George’s affective instability continued, but his thought disorder and psychosis have been the most enduring symptoms, even in the absence of mood dysregulation. His comorbid diagnosis was changed to schizoaffective disorder and, more recently, to schizophrenia. He is currently taking a typical antipsychotic. His thoughts are more linear, he rarely talks about “she,” and he is much more able to engage in his schoolwork.

Although George’s psychotic symptoms are well controlled by the medication, symptoms of ASD persist, including poor eye contact, ongoing failure to develop appropriate peer relationships, inability to sustain a conversation with others, encompassing preoccupation with restricted patterns of interest, stereotypies, and repetitive motor mannerisms. These symptoms, present since early childhood, predated his symptoms of psychosis and continue to require the support of autism-specific services.

Genetics

Although epidemiological studies of the genetic relationship between autism and schizophrenia are deficient, evidence does exist for shared genetic factors.20 As with the majority of psychiatric disorders and other common conditions, genetic complexity is compounded by phenotypic complexity. Copy number variant and rare allele studies have found a relationship between autism and point and structural mutations in neurologins, neurexins, and related genes.7 There have also been reports that implicate the neurexin family in schizophrenia. Neurologins are a family of postsynaptic proteins that bind transsynaptically to neurexins, which are presynaptic proteins that seem necessary for both excitatory and inhibitory synaptogenesis and synapse maturation. This fits with the neurodevelopmental insult and imbalance in excitatory and inhibitory transmission hypothesis for both autism and schizophrenia.20

Specific deletions associated with schizophrenia include 22q11.2, 1q21.1, and 15q13.3, which have been found to be associated with autism, attention-deficit disorder, and mental retardation.20 In individuals with velocardiofacial syndrome (chromosome 22q11), rates of ASD and psychosis are higher.21 Similarly, 16p11.2 microdeletions or microduplications have been reported in 1% of cases of autism and in 2% of the NIMH COS cohort.22-24 These copy number variants confer a risk for a range of neurodevelopmental phenotypes that include autism and schizophrenia.20 Although there have not been systemic comparisons of genome-wide association studies for autism and schizophrenia, some functional links have been reported at voltage-gated calcium channel genes, which are integral to presynaptic function and plasticity, across phenotypes.20

Brain changes

Both autism and schizophrenia have accelerated trajectories of brain development around the age of symptom onset: those with autism have an acceleration or brain overgrowth during the first 3 years of life, and those with COS have an acceleration of brain development (pruning) during adolescence.7

Cheung and colleagues25 attempted to quantify brain structural similarities and differences in ASD and schizophrenia using a quantified anatomical likelihood estimation approach to synthesize existing brain imaging datasets. Using this model, they extracted 313 foci from 25 voxel-based studies comprising 660 patients (308 ASD, 352 first-episode schizophrenia) and 801 controls. Those with ASD and schizophrenia had lower gray matter volumes within limbic-striato-thalamic neurocircuitry than did controls. Unique features included lower gray matter volume in the amygdala, caudate, and frontal and medial gyrus for schizophrenia, and lower gray matter volume in the putamen for autism. The researchers concluded that in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms.25

Treatments

A variety of psychosocial and educational interventions that support children with COS and children with ASD exist to address core deficits in socialization, communication, and behavior and the associated developmental and medical conditions. A thorough description is beyond the scope of this article, however. Atypical antipsychotics are the mainstay of pharmacotherapy for schizophrenia at any age, and they have also been used to manage certain symptoms, particularly irritability, associated with ASD.26-28

Conclusion

Developmental delays are described premorbidly in samples of children and adults with schizophrenia. More recently, the notion that ASD and schizophrenia can present comorbidly in a subset of patients has received further attention in the literature.7,29 Yet our current diagnostic hierarchy implies that the two conditions are distinct.

The differential diagnosis between these disorders and the comorbid diagnoses of the two conditions is often a bit of a quagmire for clinicians. Our program is frequently asked to rule out ASD, schizotypal personality disorder and/or schizophreniform disorder, and first-episode schizophrenia in youths and young adults. We see children with ASD who have emerging psychotic symptoms. In these children, the hallucinations or delusional preoccupations may initially be attributed to the developmental disorder. Conversely, we also see adolescents or young adults with schizophrenia who have a developmental history consistent with ASD (typically higher functioning) and who continue to have comorbid ASD. Yet some have not previously received a diagnosis of ASD. Appropriate identification of comorbid conditions can enhance intervention efforts (eg, autism-related services for those with comorbid ASD and/or use of antipsychotics in patients who have comorbid ASD and a psychotic disorder).

The key take-away point is that there are some individuals who may have both COS and ASD. Adult psychiatrists and mental health professionals would benefit from further training in the diagnosis of ASD in adults, and child mental health professionals would benefit from training in the diagnosis of schizophrenia spectrum disorders in youths. Given the complex symptom profile in youths with schizophrenia spectrum disorders, there tends to be a delay in diagnosis, even when symptoms are present for years.30 In addition, child mental health professionals would benefit from training in more specific identification of primary psychotic disorders in youths with ASD. Finally, care must be provided in an integrative manner—using a biopsychosocial model—for these multicomplex patients and their families.

Systematic long-term follow-up studies that include individuals with ASD and with COS are indicated to further inform the field regarding similarities and differences between autism and schizophrenia. These studies would benefit from the inclusion of genetics and characterization of family members to get a clearer sense of the genotype-phenotype associations and predictors of outcome.

REFERENCES

References

1. Kanner L. Autistic disturbances of affective contact. Nervous Child. 1943;2:217-250.
2. Kolvin I. Studies in the childhood psychoses. I. Diagnostic criteria and classification. Br J Psychiatry. 1971;118:381-384.
3. Rutter M. Childhood schizophrenia reconsidered. J Autism Child Schizophr. 1972;2:315-337.
4. Volkmar FR, Cohen DJ. Comorbid association of autism and schizophrenia. Am J Psychiatry. 1991;148:1705-1707.
5. Kolvin I, Ounsted C, Humphrey M, McNay A. Studies in the childhood psychoses. II. The phenomenology of childhood psychoses. Br J Psychiatry. 1971;118:385-395.
6. Watkins JM, Asarnow RF, Tanguay PE. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry. 1988;29:865-878.
7. Rapoport J, Chavez A, Greenstein D, et al. Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. J Am Acad Child Adolesc Psychiatry. 2009;48:10-18.
8. Sporn AL, Addington AM, Gogtay N, et al. Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness? Biol Psychiatry. 2004;55:989-994.
9. Asarnow RF, Brown W, Strandburg R. Children with a schizophrenic disorder: neurobehavioral studies. Eur Arch Psychiatry Clin Neurosci. 1995;245:70-79.
10. Alaghband-Rad J, McKenna K, Gordon CT, et al. Childhood-onset schizophrenia: the severity of premorbid course. J Am Acad Child Adolesc Psychiatry. 1995;34:1273-1283.
11. Posey DJ, Kem DL, Swiezy NB, et al. A pilot study of D-cycloserine in subjects with autistic disorder. Am J Psychiatry. 2004;161:2115-2117.
12. Berney TP. Autism—an evolving concept. Br J Psychiatry. 2000;176:20-25.
13. Towbin KE, Dykens EM, Pearson GS, Cohen DJ. Conceptualizing “borderline syndrome of childhood” and “childhood schizophrenia” as a developmental disorder. J Am Acad Child Adolesc Psychiatry. 1993;32:775-782.
14. Klin A, Mayes LC, Volkmar FR, Cohen DJ. Multiplex developmental disorder. J Dev Behav Pediatr. 1995;16(3 suppl):S7-S11.
15. Buitelaar JK, van der Gaag RJ. Diagnostic rules for children with PDD-NOS and multiple complex developmental disorder. J Child Psychol Psychiatry. 1998;39:911-919.
16. Van der Gaag RJ, Buitelaar J, Van den Ban E, et al. A controlled multivariate chart review of multiple complex developmental disorder. J Am Acad Child Adolesc Psychiatry. 1995;34:1096-1106.
17. van der Gaag R, Caplan R, van Engeland H, et al. A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders. J Child Adolesc Psychopharmacol. 2005;15:465-476.
18. de Bruin EI, de Nijs PF, Verheij F, et al. Multiple complex developmental disorder delineated from PDD-NOS. J Autism Dev Disord. 2007;37:1181-1191.
19. Sprong M, Becker HE, Schothorst PF, et al. Pathways to psychosis: a comparison of the pervasive developmental disorder subtype multiple complex developmental disorder and the “at risk mental state.” Schizophr Res. 2008;99:38-47.
20. Carroll LS, Owen MJ. Genetic overlap between autism, schizophrenia and bipolar disorder. Genome Med. 2009;1:102.
21. Vorstman JA, Morcus ME, Duijff SN, et al. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry. 2006;45:1104-1113.
22. Walsh T, McClellan JM, McCarthy SE, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008;320:539-543.
23. Kumar RA, KaraMohamed S, Sudi J, et al. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet. 2008;17:628-638.
24. Shen Y, Dies KA, Holm IA, et al; Autism Consortium Clinical Genetics/DNA Diagnostics Collaboration. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. 2010;125:e727-e735.
25. Cheung C, Yu K, Fung G, et al. Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation. PLoS One. 2010;5:e12233.
26. Madaan V, Dvir Y, Wilson DR. Child and adolescent schizophrenia: pharmacological approaches. Expert Opin Pharmacother. 2008;9:2053-2068.
27. Masi G, Mucci M, Pari C. Children with schizophrenia: clinical picture and pharmacological treatment. CNS Drugs. 2006;20:841-866.
28. McDougle CJ, Stigler KA, Erickson CA, Posey DJ. Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders. J Clin Psychiatry. 2008;69(suppl 4):15-20.
29. Stahlberg O, Soderstrom H, Rastam M, Gillberg C. Bipolar disorder, schizophrenia, and other psychotic disorders in adults with childhood onset AD/HD and/or autism spectrum disorders. J Neural Transm. 2004;111:891-902.
30. Frazier JA, McClellan J, Findling RL, et al. Treatment of early-onset schizophrenia spectrum disorders (TEOSS): demographic and clinical characteristics. J Am Acad Child Adolesc Psychiatry. 2007;46:979-988.
- See more at: http://www.psychiatrictimes.com/autism/autism-and-schizophrenia#sthash.HYAeK00N.dpuf

 

[H-KQGE]

Now over to this piece showing shared genes (& overlaps in neurodevelopment) where ADHD, Intellectual Disability, Dyslexia & Epilepsy (as part of neurological & mental disorders) might fit with regards to truncated proteins.

A research identifies novel autism candidate genes
The research group in which researchers Bru Cormand, Claudio Toma, Amaia Hervás, Conchita Arenas and Alba Tristán collaborate.
The research strengthens the idea that many mental and neurological disorders share some genetic factors.

23/10/2013
Recerca

A scientific study published on the journal Molecular Psychiatry identifies new genes involved in autism, a polygenic disorder that is difficult to diagnose and treat. Researchers who participated in the research are: Bru Cormand, Claudio Toma, Bàrbara Torrico and Alba Tristán, from the Department of Genetics and the Institute of Biomedicine of the UB (IBUB), affiliated centres with the campus of international excellence BKC; Concepció Arenas (Department of Statistics of the UB) and Mònica Bayés, researcher from the National Centre for Genome Analysis (CNAG), located at the Barcelona Science Park (PCB-UB), and the groups led by Amaia Hervás, coordinator of the Child and Adolescence Mental Health Unit at the Mutua de Terrassa University Hospital, and Marta Maristany, from Sant Joan de Déu University Hospital, affiliated centres with the campus of international excellence HUBc.

Looking for new candidate genes

Autism spectrum disorders (ASDs) represent a group of neurodevelopmental disorders which affect one out of 80-100 children. Autism’s aetiology remains mainly unknown but there is strong evidence that genetic factors play a major role. An active international research has been carried out for several years in order to identify candidate genes which explain the origin and development of the disease.

Bru Cormand, head of the Research Group on Neurogenetics at the Department of Genetics of the UB, affirms that “studies made with monozygotic (genetically identical) and dizygotic twins show that genetic factors play a major role in the aetiology of the disease”. Therefore, “if a monozygotic twin has autism, the likelihood that the other twin also has the disease is 60-90%; however, if they are dizygotic twins, the probability is reduced up to 20%”, states the expert. This proves that genetic factors play a major role in the aetiology of the disease, but the association between the disease and one person’s set of mutated genes remains uncompleted.



Inherited mutations in autism: a new perspective

To date, studies on autism genetics were mainly focused on de novo mutations —the ones that appear in a child but they are not present in progenitors— in families with one child affected. However, the work published on Molecular Psychiatry and first signed by the expert Claudio Toma provides an innovative view on the study of ASDs genetics: “It is the first time that mutations transmitted to children by any of the progenitors are studied in a genomic perspective. In total, ten families in which two or three children have autism were analysed”, details Bru Cormand.

The research is based on whole exome sequencing (WES), which is the part of the genome translated into proteins. This innovative and quite recent technique is a really effective strategy to diagnose hereditary diseases. The study, which has identified more than 200 rare variants inherited by children, determines that genes YWHAZ and DRP2, among others, are new candidates in the research on autism genetic basis.

The research shows that most frequent mutations are the ones which give rise to truncated proteins, shorter and non-functional. Some of the genes identified in the study are also mutated in patients of other neurological and mental disorders (epilepsy, attention deficit hyperactivity disorder, intellectual disability, dyslexia, etc.). “For instance, the gene YWHAZ, involved in neuronal migration and plasticity, is associated with other diseases such as schizophrenia”, explains Cormand. “Therefore, findings support —adds the researcher— the idea that genetic factors play a major role in these diseases”. Moreover, according to Claudio Toma, “more inherited truncated mutations mean lower intelligence quotient in an autistic person”.


Autism: a cumulative effect

The research shows that children need to inherit a certain number of variants in order to develop autism. “Inherited genetic factors may have a cumulative effect; therefore, the disease would only appear if a certain number of variants are inherited”, explain researchers. Interaction between different affected genes may also occur; this should be investigated in the future.

To identify the genes associated with autism spectrum disorders is fundamental to find targets to develop effective treatments for patients. It is necessary to promote new projects to define patients’ genetics, identify which are the most important genes and develop new genetic diagnosis tools.

Cormand points out that “genetic profile will not be identical in all patients, but we hope to find a shared part”. The researcher concludes that “there is plenty of work to do in order to attain a genetic diagnosis of the disease; however if genetic basis knowledge goes further, new therapeutic intervention could be fostered and autism will stopped to be only treated by palliative and unspecific strategies”.

This research was supported by La Marató de TV3, the Spanish Ministry of Economy and Competitiveness, the Alicia Koplowitz Foundation and the Centre for Biomedical Network Research on Rare Diseases (CIBERER).

From the image you can see that ASD engulfs all else apart from ADHD. To Psalehesost I have to say that I had a parsing problem with the link you provided. Seeing as some of this is awfully close to what you posted, & I couldn't access the paper, I apologize in advance if it is the same.

 

[Laura]

Here are a couple of studies on schizophrenia which might give more clues as to the abnormalities:

Circular inferences in schizophrenia

_http://brain.oxfordjournals.org/content/136/11/3227.abstract.html?etoc

<snip> Considering that the brain constructs hierarchical causal models of the external world, we show that the failure to maintain the excitatory to inhibitory balance results in hallucinations as well as in the formation and subsequent consolidation of delusional beliefs. Indeed, the consequence of excitatory to inhibitory imbalance in a hierarchical neural network is equated to a pathological form of causal inference called ‘circular belief propagation’. In circular belief propagation, bottom-up sensory information and top-down predictions are reverberated, i.e. prior beliefs are misinterpreted as sensory observations and vice versa. As a result, these predictions are counted multiple times. Circular inference explains the emergence of erroneous percepts, the patient’s overconfidence when facing probabilistic choices, the learning of ‘unshakable’ causal relationships between unrelated events and a paradoxical immunity to perceptual illusions, which are all known to be associated with schizophrenia.

And:

Adding somewhat to the recent above information but from 2011...

Autism and Schizophrenia

<snip>
When higher-functioning individuals with autism are stressed, they become highly anxious and at times may appear thought-disordered and paranoid, particularly when they are asked to shift set (such as being asked to change a topic of conversation or to stop an activity that they are engaged in and begin a new activity). <snip>

I've just recently finished reading Jerome Carcopino's tour de force analysis of Marcus Tullius Cicero and, at the end, I am convinced that the individual that emerges is most certainly a schizoid psychopath. Because the evidence that is presented comes from almost a thousand preserved letters and many volumes of writings that have been preserved, it is a MOST interesting study. Carcopino literally takes you inside the mind and reality of Cicero in a way that is similar to how Cleckley takes you into the world of the garden variety psychopath. Even though Carcopino is not examining his subject with a view to exposing his psychopathology, that is the end result. He is rather taking more of a humanistic approach as Lobaczewski describes being inadequate to truly understand what is being seen, though I doubt Lobaczewski thought that Cicero was such a type and that Caesar was NOT. Because we notice that Lobaczewski mentions Caesar as having epilepsy and I have yet to find any convincing evidence that he did. He only had a couple of "spells" in his later life which appear to me to have been mini-strokes due to extreme and prolonged stress.

Anyway, as I said, in view of the discussion to hand, I think that the case study of Cicero as presented by Carcopino will be furiously interesting to all who are intrigued by this sort of thing. It is a dynamic and engaging work and I guarantee that you will not be bored by some dry, academic writing.

 

[obyvatel]

Schizothymia


Ernst Kretschmer described a schizothymic personality which was once viewed as a milder strain of the schizoidal type. Schizothymic individuals could be hypersensitive and their tendency towards social isolation was a result of defensive withdrawal and sense of vulnerability to intense stimuli. They would have more theoretical than practical abilities. Kretschmer noted the preponderance of schizothymic personality types among philosophers and metaphysicians. “Schizo” is derived from schism or split. Schizothymic psyche can be split into a private mental domain alienated from the body and external reality. The private mental domain is felt as more real and vital than the body and external reality. One possible consequence of schizothymia is an attitude of emotional detachment and intellectual superiority which when amplified could turn into “solipsistic omnipotence” (only one’s own mind is real). Brings to mind the Cartesian “I think therefore I am” mindset.

Dabrowski noted that schizothymic personalities can have tendencies towards internal conflict. Internal conflict is a necessary condition for personality development and includes dissatisfaction and feeling of inferiority within oneself compared to a higher internal standard. This is in contrast with external conflict where feelings of inferiority can be aroused from clashes with the external world. A schizothymic personality undergoing positive disintegration would develop interest in other people, adapt better to external environment, and experience a diminution of the exclusiveness of one’s own norms.

In the absence of positive disintegration and development of personality, a schizothymic personality can possibly solidify the traits of emotional detachment and intellectual egotism. When such people reach high positions in fields like philosophy and metaphysics (as noted by Kretschmer), the result is generation of theories which are alienated from life and reality. I think this is what Gurdjieff referred to in Beelzebub’s Tales as “learned beings of the new formation having hasnamussian (psychopathological) tendencies”.