SchizophreniaWatch

A UK website, principally for carers about and carers for schizophrenia; family, community, and professional service caring, who should - must ! - give voice for the best interests of those cared for they can't, they won't, they don't, voice for themselves
The site is edited by a retired psychiatrist who has looked after someone with the schizophrenia condition, at home, affected by the negative form of schizophrenia, for the last twenty years. [The blue highlit links take you to another page.. ] You return via the back arrow at the top of your screen or from a link at the bottom of a page

contact me if you want to help me out with my views, email about some issue of caring service that is promising, or unsettled and unsettling or text to (44) (0)7547153244
There is a limited general psychiatry section .... links

The academic papers that explains this and why and /how the illness continues to be, are put together on a companion website.
schizophreniabrain


New this month:-December

A research team, from Harvard, Columbia and California universities, set out to test whether adolescents' typical reward-seeking behaviour could also make them better at learning from good or bad outcomes.
They asked 41 teenagers, aged 13 to 17, and 31 adults, aged 20 to 30, to play a game based on pictures while scanning some of each group's brains using MRI.
In the game, the teenagers got more answers correct and memory tests showed they were also better at remembering the detail of why they chose the answers they did.The study said this meant they were better at learning from their experiences - which would equip them well for leaving home and gaining independence as adults. adults mainly used their striatum.


November
1. ED:- Is this adolescent pruning? McCarroll
In the blood, C4 complement binds to microbes to signal that they should be eaten by immune cells.

C4 has a second role in the brain.
C4 binds to neurons at the points where they connect with other neurons, and signals that these synapses, should also be engulfed by immune cells.

2.Larry J. Seidman, PhD, a psychologist at BIDMC and professor of psychology at Harvard Medical School.
"Our group's focus is on identifying early warning signs and then developing interventions to improve a person's chances for not getting it, [ it being schizophrenia} making it milder or delaying it."


Impaired working memory (the ability to hold information like a phone number in mind for a short time while it's in use) and declarative memory -
the ability to recall things learned in the last few minutes) turned out to be the key neurocognitive functions that are impaired in the high-risk, prodromal phase difficulties reading, concentrating or remembering things in the earliest days of the disorder.


*** EditorThat is what would happen if hippocampus new cell proliferation failed to maintain a flow of new cells.*
memory ]
Working memory can help us overcome a particular problem or perform a task, like mental arithmetic, using a phone number or following a set of directions e.g to apply for rehousing or benefits.
However the amount of information we can hold is limited and the information itself is very unstable - a sudden distraction and the information is lost and you have to start again from scratch.
Working memory is essential for learning and development.

The hippocampus matches what was going on before, of personal significance, already in the memory store of experience, with what is going on outside the brain now. The temporary nature of what the the new cells hold prevents any overload of unwanted incoming information.

Only what is of value adding use is allowed in through the hippocampus connection.
Less hippocampal new cells activity = poor recent memory.
A reduction in hippocampal new cell production leads to a corresponding loss of memory performance.
[ see Coras ]



People are uncomfortable and anxious when they do not have a personal narrative that comforts them with a position in their society - an identity -a coherence within the world around them.

[ Gazzaniga studied split brains i.e. the right and laft brain cannot communicate with each other, normally.
Gazzaniga developed what he calls the interpreter theory to explain why people — including split-brain patients — have a unified sense of self and mental life3. It grew out of tasks in which he asked a split-brain person to explain in words, which uses the left hemisphere, an action that had been directed to and carried out only by the right one. “The left hemisphere made up a post hoc answer that fit the situation.” In one of Gazzaniga's favourite examples, he flashed the word 'smile' to a patient's right hemisphere and the word 'face' to the left hemisphere, and asked the patient to draw what he'd seen. “His right hand drew a smiling face,” Gazzaniga recalled. “'Why did you do that?' I asked. He said, 'What do you want, a sad face? Who wants a sad face around?'.” The left-brain interpreter, Gazzaniga says, is what everyone uses to seek explanations for events, triage the barrage of incoming information and construct narratives that help to make sense of the world.

For schizophrenia, the only narrative available to them when their hippocampus new cell proliferation is reduced, is that they are continually confused, and made anxious - by information overload - some incoming information stimuli from the environment - that the hippocampus mmory stream would ignore = gets into the striatal memory stream - shouldn't be there so has a 'fear' value put on it - leading to the delusional explanation.

How would that come about?
Because those with schizophrenia are trying to deal wih all the incoming stimuli from their environment with HALF ONLY, of the proliferation that their normal peers require to cope with all the changes that happen within day -to- day living.

They suffer from information overload,

When there is information overload some stimuli are not dealt with by the hippocampus memory route but escape that scrutiny, going directly into the striatal memory route. It should not be there.[ Disruption of hippocampal function can enhance striatum-dependent learning. ]
That route stamps the abnormal incoming stimuli with emotional value, dealing with this alarming strangeness by developing a coherent but delusional narrative explanation.Foerde et al


Page 2. helping with the illness ]

The Cause of continuing Schizophrenia.

Family carers, and professional carers, must get to know all about the hippocampus area of the brain. My apologies for the many repetitions in what follows but overread is better than otherwise

Because. at illness onset, the volume of the hippocampus in schizophrenia is reduced, - the change in the schizophrenic brain most likely happens at the start of the illness

Das et al dental gyrus
These data suggest that the dentate gyrus [ of the hippocampus ] is dysfunctional in schizophrenia, a feature that could contribute to declarative memory impairment in the disorder and possibly to psychosis, a conclusion consistent with the considerable molecular pathology in the dentate gyrus in schizophrenia".

two studies show changes preceding schizophrenia
1.Schobel et al
1.hippocamapal glutamate
2.[ ... Archives General Psychiatry 2011 May;68(5):489-95. ... Mechelli at al.
Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study.

Individuals at high risk for psychosis [ schizophrenia ] show alterations in regional gray matter volume regardless of whether they subsequently develop the disorder.

In the Ultra High Risk population, reduced left parahippocampal volume was specifically associated with the later onset of psychosis.

Alterations in this region may, thus, be the start of schizophrenia]


The hippocampus area of the brain in continuing schizophrenia is producing only half the number of new cells that the normal hippocampus proliferates.

[ The consequence :-

Coras et al:- Brain 2010:see 133; 3359 ....
A correspondence is found between the level of human hippocampal neurogenesis cells and the level of effective working memory.
The researchers studied how stem cells in a memory-related region of the brain, called the hippocampus, proliferate and change into different types of nerve cells.
Scientists have been unsure of the significance of that process in humans.

Over the past two decades, several studies have shown that new nerve cells are generated in the hippocampus.
In animal studies, disrupting nerve cell generation resulted in the loss of memory function, whilst increasing the production of new nerve cells led to improved memory.

To investigate whether the same is true in humans, the UF researchers, in collaboration with colleagues in Germany, studied 23 patients who had epilepsy and varying degrees of associated memory loss.
They analyzed stem cells from brain tissue removed during epilepsy surgery, and evaluated the patients' pre-surgery memory function.
In patients with low memory test scores, stem cells could not generate new nerve cells in laboratory cultures, but in patients with normal memory scores, stem cells were able to proliferate.

That showed, for the first time in human tissue a clear correlation between patient's memory and the ability of their stem cells to generate new nerve cells. ]


The hippocampus in schizophrenia is proliferating half only of the amount of new cells that their normal peers require to cope with the problems of daily living

Reif et al 2006 Allen et al
In two Studies in catchment area samples, of all those with continuing schizophrenia, 80% show poor memory management [ Al-usri et al 2006}
The hippocampus uses new cells to see to it that, of the multitude of information stimuli coming in from outside perception, only that which is new and of value for the person's usefully stored experience, are moved into consolidation with longterm memory.
Continual new cells in the hippocampus hold new information, with its context, for a time, after which they are replaced by other new cells, ready to take in any furtherchanges from incoming environment stimuli, to update those changes into working experience
The hippocampus is part of the working memory process that makes available what it is from stored experience that gives the context, for dealing with whatever is currently going on in their lives.


The hippocampus plays an important role in learning and memory processes.
It is the region where incoming sensory information converges with stored memories. Interaction of these two currents is an essential principle of organised thinking.
Encoding allows the perceived item of interest or usefulness to be formulated in a way that can subsequently be placed with experience previously stored, whilst available to be called upon to give the context in completing the sequence of any intended action now or in the future All sensory information passes through a trisynaptic pathway formed by the entorhinal cortex, dentate gyrus (DG), CA3 and CA1 regions. CA1 region provides a comparison of patterns or predictions formed in CA3 region with "sensory reality" i.e. with the inputs from the entorhinal cortex .
Working memory stores information for immediate use or manipulation which is aided through hookingit onto previously archived items already present.
Memories are a combination of old and new information, so the nature of any particular memory depends as much on the old information already in our memories as it does on the new information coming in through our senses. In other words, how we remember something depends on how we think about it at the time.

Because of the replication by Allen et al, in 2015 of the finding by Reif et al in 2006( vide infra ), ,
it is now a fact - that those with continuing schizophrenia have to try to manage normal day to day living , to complete the sequence of their intentions,
with HALF only, of the hippocampal new cell proliferation that theirnormal peer groups requireto be able so to do.


The brain loses the ability to tune out information that isn't useful or relevant. They become overwhelmed by the inflow of stimuli from the environment.
They are walking down the street trying to have a conversation and their brain is being flooded with the sound of the door slamming, the airplane going overhead,;says Vinogradov, of the San Francisco VA hospital
. The brain is starting to process all of that information as if it has meaning, that it is something the brain needs to pay attention to and needs to do something about.

Maybe, the theory goes, that's what gives rise to hallucinations and delusions.
The mind seeks a narrative explanatio for the extra data coming in.If you pay attention to everything,says UCSF Sohal, you might start paying attention to and believe in coincidences.You might get paranoid. Or you might pay even more attention to your own thoughts and start thinking, "These are other peoples thoughts".
In schizophrenia, the selection of what to attend to, and to organise it into retrievable useable experience , has to be done with half only of the hippocampusnew cells that are ordinarily made available.
The continual updating and storing of useful experience does not happen. They cannot move on in their lives as they should, stuckwith only the experience stored before the illness arrives.
When schizophrenia arrives during adolescence and early adulthood, they have not the level of stored experience to cope with a daily world that brings new matters to be dealt with in daily living.
Those with their illness arriving in later life, are already better equipped in matured experience to cope better.
Q.
What has happened to bring about schizophrenia? A.
The crucial failure.

The disabling brain change is a failure to sustain new cell formation[ <[I>neurogenesis] in thehippocampus area of the brain.
This is the change in the brain that leads into continuing schizophrenia
Reif et al 2006 - Reif et al 2006the most important finding
Replicated and now - 9 years late -Confirmed ! !It must now be accepted. by Allen et al :- - if linking is difficult - this is the Quote
We find a decrease in cell proliferation in the anterior hippocampus of people with schizophrenia, confirming the results of previous studies that have suggested a deficit in hippocampal cell proliferation and of neurogenesis in schizophrenia [ Reif et al ] in an independent cohort. Our results are consistent with those of Reif; however, we found a slightly larger decrease in Ki67 expression, 60% in the current study vs. 50% in Reif et al. ]


In those with schizophrenia, there is a stem cell failure of new cell proliferation in the hippocampus of the brain . Normally the hippocampus new cells function as ' a gatekeeper' to take from incoming environment observations - whats new, whats going on outside around me - only what is a useful addition to stored away skill and experience. The new cells hold on to it temporarilyuntil it is consolidated with what is already stored longterm. The new material may be advantageous, or 'seen' a possible 'threat' that will need future attention and so has to be stored as experience
What is taken in from 'outside' comes with its useful context.
Once consolidated in the brain long term memory the temporary new information fades away leaving succeeding new cells to continue the updating.
Once the information is updated, the hippocampus will later take part in retrieving from store whatever context information is to be carried 'in mind' so as to deal with what ever crops up in daily living , putting together in sequence the relevant contexts to whatever is happening.
Sufferers from schizophrenia have to try to manage daily life problems, and these life coping decisions with half onlyof the amount of new hippocampal cells that those without illness NEED to have available so as to be able deal and move on in their lives.
Without enough hippocampal new cell provision they cannot disentangle all the incoming environmental stimuli. They will experience incoming stimulus information overload from their environment.
Foerde et al
[ Here, we present results from functional neuroimaging showing that the presence of a demanding secondary task during learning modulates the degree to which subjects solve a problem using either declarative memory or habit learning. Dual-task conditions did not reduce accuracy but reduced the amount of declarative learning about the task. Medial temporal lobe activity was correlated with task performance and declarative knowledge after learning under single-task conditions, whereas performance was correlated with striatal activity after dual-task learning conditions. ]
People with schizophrenia are less able 'to see to it' that the 'useful' goes to the flexible hippocampal consolidation stream, the chaff 'noise' excluded.
The chaff goes tothe striatum memory route.The brain is starting to process all of that information as if it has meaning, and is something the brain needs to pay attention to and needs to do something about.
Maybe, the theory goes, that's what gives rise to hallucinations and delusions.
The mind seeks explanations for the extra data coming in.

If you pay attention to everything,says UCSFSohal, you might start paying attention to coincidences, and you might get paranoid. Or you might pay even more attention to your own thoughts and start thinking, 'These are other peoples thoughts.

With half only of the new cells in the normal hippocampus, some non salient incoming sensory material will bypass the hippocampal stream, instead getting into the striatal procedural stream , to be wrongly consolidated as salient material , which will not make sense, will carry anxiety.
fear consolidation..... So it is likely go to consolidation in REM sleep, to be made 'sense' of, as a delusional system, relatively inflexible, taking over under circumstances of any future stress or unresolved anxiety.
Information gets into the wrong memory stream, and is less flexibly available


Calling up from memory store what is required to be able to react with the background experience to things that need attention, get insufficient context to any intention that is to be executed.
They do not move on in their lives, stuck at the level of ability and useful experience that they have at the age the illness arrived.
Information that passes the hippocampal new cell sorting 'office', will be consolidated in another memory stream tthrought the different route which deals with automated network storage , into an autonomous delusional explanation.


Those who go on to continuing schizophrenia do so because the hippocampus region in their brain - the gate-keeper of convergence between the inside and the outside world - has to manage this with half only of the new cell provision to the hippocampal functioning that heathy people need to be available to be able to cope with all the changes in day to day living - sorting out the wheat - necessary, from the chaff - ignorePeople with continuing schizophrenia suffer from incoming information overload [ as with normal people ....foerde] with poor background context

That is why reducing the information load in a daily life, providing a routine, in a reduced setting helps, where regularity and repetition, with plenty of uninterrupted time and less going on around them, is a relieving care situation. The hippocampal gate-keeping function - keeping out irrelevant information whilst allowing in useful experience - can't cope with only half the usual hippocampal new cell provision - its anxiously unsettling - letting some incoming stimuli to go directly, 'uncensored ' ,
into the striatal memory net work - normally used for procedural learning - habits - grammar bicycle riding: relative to the hippocampal stream where stored material can be consciouly sought, the striatal route is less flexible, less conscious, less accessible, uses a different net work to consolidate what it has taken in, and where dopamine imprints value on what is passing through.
Stand out material that gets into storage this way is abnormal, carries anxiety with it, yet has to be dealt with , given an account in some way - so becomes consolidated as an explanatory delusional system, normally segregated , but returned to whenever stress/anxiety returns dreaming, cortisol and anxiety



Less intact 'working memory' means that, at the age the illness arrives, they do not , cannot, move on in their lives.
The earlier the illness arrives the less accumulated store of experienced information is there to cope with what crops up during the day .
Schizophrenia arriving later will have already acquired a store of living experience, will cope better., even though retaining delusional influence.

An active working memory is what keeps you up to date: keeps you going. Without new cell proliferation in the hippocampus workimg memory is not sustained.


When and how does the brain change happen. ? perinatal damage

Maybe pruning failure
Nature. 2016 Feb 11;530(7589):177-83. doi: 10.1038/nature16549. Epub 2016 Jan 27. Schizophrenia risk from complex variation of complement component 4. Sekar A,

fHEATHER DE RIVERA :- Compared to the brains of healthy individuals, those of people with schizophrenia have higher expression of a gene called C4, [ a part of Complement structures in immunity responses ] according to a paper published in Nature C4 today (January 27). The gene encodes an immune protein that moonlights in the brain as an eradicator of unwanted neural connections (synapses). The findings, which suggest increased synaptic pruning is a feature of the disease, are a direct extension of genome-wide association studies (GWASs) that pointed to the major histocompatibility (MHC) locus as a key region associated with schizophrenia risk.