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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

Page 2.
getting nowhere

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


page 4 ......

This is my understanding of the background to the development of schizophrenia: its proximate cause, it's treatment, it's Care.

contact me if you want to help me out with my views, email me [ contact me if you want to help me out with my views, email me: at
email me

There is a limited general psychiatry section .... links

The academic papers that explain why and how the illness continues to be, are put together on a companion website.
schizophrenia brain
[ apologies if this link may not work - go to www.brainandschizophrenia.co.uk ]


New

February :-
1. applying importance to what has been perceived.

2. information overload

People with schizophrenia often develop what is labelled a primary delusion.Something that other people perceive as insignificant or banal, is given a high significance, a meaning that is made acceptable,'satisfied', only by developing a narrative explanation [ the delusion ] which would not be given normally.
The above reference studied how applying meaning comes about to what has been perceived.examined how and where the false perceptions created by the hallucinatory drug LSD were received in the brain. They discovered that a particular receptor system , a serotonin target receptor if blocked, prevented the hallucinatory experience. 'Significant ' needed a serotonin involvement
That particular serotonin receptor was necessary for accepting the hallucination as having a significance - a meaning.

If serotonin was needed for generating [ ? 'allowing ' ] new meaning, the dopamine system might regulate the relevance of any stimuli the recipient might 'deem' emotionally important.

January 2017
1.
automated freespeech examination predicts schizophrenia

December 2016


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 and destroyed by immune cells.

December 2016

2.
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 god 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.

When they looked at the teenagers' brain scans, the researchers found activity in two areas of the brain - the hippocampus and the striatum -In everyday life, they're paying attention to their environment in a way that is different from adults."

whereas adults mainly used their striatum. ? Adults are calling upon much already stored experience: adolescent have yet to acquire that for prompt usage
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 (i.e. the ability to hold information like a phone number in mind for a short time while it's in use) and impaired declarative memory -
i.e. - 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 These findings, said Seidman, are in keeping with the experiences of many people with schizophrenia who report sudden 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.
* see below

This is what did happen.

Schizophrenia is a brain illness

The abnormality change is in the hippocampus area of the temporal lobe in the brain, the area that proliferates new cells. [ i.e. neurogenesis ]

glutamate hyperactivity precedes overt schizophrenia It is succeeded by a hippocampal size reduction that persists

Because the hippocampus volume is reduced at the start of the illness it is likely the changes occur at that time
Das et al dental gyrus
This data suggest that the dentate gyrus [ in the hippocampus ] is dysfunctional in schizophrenia, a feature that could contribute to declarative memory impairment in the disorder and possibly to psycho

New cell making in the hippo-campus is reduced in schizophrenia.

Reif et al 2006 [ Reif et al :- Molecular Psychiatry (2006) 11, 514-522 ]
Reif et al is now confirmed by Allen et al 2015
Allen et al 2015

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 [ prospective memory ]

[ If linking to the main Allen et al paper is difficult.. go to this Quote - from Allen et al - .

" 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 " ( i.e. 60% in the current study vs 50% in Reif et al ]

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.
These new hippocampus cells are a necessary part of getting new experience, with current useful information, adopted and then stored in longer term memory.
People who continue with schizophrenia have only half the normal value of new cells to do that job.


For family carers and professional NHS mental health teams,
knowing about hippocampus failure is the key to a proper understanding of the behavioural changes that come in those with schizophrenia

The hippocampus continually provides new neurons on a temporary basis. This the critical function. Their particular job done, they make way for other new cells
It supports memory at work - that is
- the ability to retrieve, hold and use a limited amount of information in our heads for a short amount of time. This is required for meeting the changes in day to day living [ read this topic introduction :- prospective [ memory ]New cells are for making and adding new experiences into store, so that they can be recalled and used when taking future intentions into completion.

Page 2. Appreciating the nature of the disability in this illness ]


Working memory can help us overcome a particular problem or perform a task, like mental arithmetic, or following a set of directions e.g to apply for rehousing or benefits.
However the amount of information we can hold in mind 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. Working memory draws on the relevant contexts into making decisions. This involves retrieval of conjoining relevant memories from longterm store.

memory retrieval

.
"Our fndings highlight the key role of the hippocampus in representing conjunctive [ connected ] information and relate this function to its importance in connecting subnetworks during memory retrieval. We demonstrate that this crucial role of the hippocampus as a connector hub is notably prevalent during memory retrieval, at the same time when conjunctive representations are reactivated"

Briefly, tasks or portions of a task with a working memory requirement are associated with increased hippocampal - median prefrontal Cortex synchrony- the area of the brain giving access to longterm store ofexperience.

Reduced synchrony is accompanied by working memory impairments.
[Axmacher et al ]

The hippocampus matches what is already in the memory store of experience, with what of personal significance is going on outside the brain now. Engaging with what is going on 'outside' needs the ability to both hold onto context, and to be able to change context to react to changing incoming information. This the critical function. As in holding a conversation, making sense of a novel, chasing the answer to a crossword clue. The gate-keeping new cells hold on only to what is new materialpreventing any distraction from unwanted incoming information.

Only what is of value, adding usefulness, is allowed in through the hippocampus connection.
Fewer hippocampal new cells in an individual, matches poor memory activity in that individual.

Confirmed in humans.
[ see Coras ] correspondence is found between the level of human hippocampal neurogenesis cells and the level of effective working memory.
Coras et al studied how stem cells in a memory-related region of the brain, called the hippocampus, proliferate and change into different types of nerve cells.
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. ]



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

why narratives win-our hearts-and minds

brain narrative

hippocampus: joining together and narrative

Gazzaniga studied people who had a surgical division of the corpus callosum - the bridge joining and linking the two halves of the brain. 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 ,set aside: instead goes directly into the striatal memory stream - it shouldn't be there so has a 'fear' value placed on.it , and therefore requires a reset to how those, now fearful, place themselves .... they have to make a new personal narrative that lets them protect their lives.[Schwabe et al:- stress and memory
- leading to the delusional narrative explanation.

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

They suffer from information overload. This happens to students concentrating on a particular subject when they have to cope with ongoing distractions.
Foerde et al
overload 2

When there is information overload some stimuli are not dealt with in 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.[Schwabe et al:- stress and memory ]
That route stamps the abnormal incoming stimuli with emotional value, dealing with this alarming strangeness by developing a coherent but delusional narrative explanation.



This paper suggests 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

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


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

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 further changes from incoming environment stimuli, to update those changes into experience, later to be drawn on in working memory, to proceed with and complete chosen intentions
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 hooking it 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.

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 explanation brain and narrative
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 social 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.
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 at sequence points 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.


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 so as 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 working 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,

HEATHER 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.