References : -

1.
Measuring memory impairment in community-based patients with schizophrenia
J. Bruce, MBChB, MRCPsych, S. Frost, MBBS, MRCPsych and D. Mackintosh, MBChB, MRCPsych
B J PSYCHIATRY 2006 189 132-13

1(a)Cognitive function in a catchment - area - based population of patients with schizophrenia
1.b CIARA KELLY, VAL SHARKEY, GARY MORRISON, JUDITH ALLARDYCE, and ROBIN G. McCREADIE The British Journal of Psychiatry 2000 v. 177, p. 348-353.
Nithsdale Schizophrenia Surveys 20

2a.
stem cell proliferation is decreased in schizophrenia, but not in depression
A Reif,, S Fritzen,, M Finger, A Strobel, M Lauer, A SchmittK-P Lesch Molecular Psychiatry (2006) 11, 514-522
Reif et al 2006


2(b)Now !2015 ! Replicated and confirmed !Allen et al


Subsequent studies [ follow below ] give confirmation - as does the inability of continuing sufferers to accumulate maturing experience after the age at which the illness - they stick in the area of interest and at the level of personal domestic and social competence they had before the illness - their friends and family move ahead and away, they are left behind.: they lose natural support and mentoring

3(a)

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.
3b.

2017Changes preceding schizophrenia

Psychiatric Times link: Seidman et al. working memory failure is early warning
seidman plus reference link


idiosyncratic speech precedes schizophrenia

as does the inability of continuing sufferers to accumulate maturing experience after the age at which the illness - they stick in the area of interest and at the level of personal domestic and social competence they had before the illness - their friends and siblings move ahead and away, they are left behind: they lose natural support and mentoring.Their lives are liable to leading to ...... information overload

3c.
Fuerte et al 2006 Information overload leads to some incoming information by-passing hippocampus memory, getting attention
[ is this the mechanism ?tobias best ],
going directly to the striatum [ putamen ] memory system.
Where somewhere, somehow, normally, it would be disposed of by the hippocampal projections as unimportant, not salient, with no consequence.
[This is the question I am struggling to know how/ what it is - in schizophrenia - about an 'ordinary' stimuli that provokes a delusional explanation - why it is singled out as that important, tha it is - wrongly- salient, goes into the longterm store experience
The network state of the perceiver, measured prior to affective experience, meaningfully influences the extent to which affect modulates memory Ref:- salience
Why/how in schizophrenia is some ordinary observed stimulus/information picked on as the impetus for a delusional explanatory narrative ? = the primary delusion of Schneider
One suggestion is that the stage is set for finding a coherent explanation, arising out of what Karl Jaspers describes as
"a general delusional atmosphere with all its vagueness of content"
- the atmosphere created from the uncertainties created when pre psychosis hippocampal proliferation fails gives insufficient control over incoming stimuli/information.

I think now, that when the anxiety caused by hippocampal failure to cope with daily living is sufficient to exhaust available responses, the brain 'decides' .. enough is enough... picks whatever 'catches the eye' - makes an explanatory narrative out of anything before you that gives a sort of stability, bringing a narrative yielding strategies that points to coping 'can do' answers. ???



4.
Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia
JM Gold, Ph.D., Hahn, Ph.D., Zhang, Ph.D. Robinson, , Kappenman, , Beck, , and Luck, Ph.D. Arch Gen Psychiatry. 2010 June ; 67(6): 570-577.
link to the Gold et al paper

5.
Automatization and working memory capacity in schizophrenia
Tamar R. van Raalten , Nick F. Ramsey , J. Martijn Jansma , Gerry Jager a, René S. Kahn / Schizophrenia Research 100 (2008) 161-171
Raalten

5.bThis study now confirmed :-
Koch et al Koch et al
"... First evidence from studies with schizophrenia patients indicates that the potential to profit from short-term practice under stable learning conditions
(ie, when the same stimulus material is repeatedly being processed)s


6.
Brita Elvevaag, Elizabeth A Maylor, Abigail L Gilbert
prospective memory and distraction [ BMC Psychiatry 2003.3.0 research article open access ]
Rehearsing a game chase test, sufferers do as well as controls - but when given a concurrent task, an overload, they fail on it, some even then declaring it was done.


7. Re Glutamate/GABA

Das et al
dental gyrus
This suggests that the dentate gyrus is dysfunctional in schizophrenia, a feature that would 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

6b.Stan et al
glutamate dental gyrus

7.
8.
hippocamapal glutamate

Schobel et al used a neuroimaging study to examine the hippocampus of people who sought psychiatric help for symptoms like mild perceptual hallucinations or delusions that did not reach the threshold of full psychosis.
[ The 'at risk' group which currently has people disputing whether to intervene to prescribe early ]
The study volunteers were imaged twice -at the beginning of the study, and again nearly 2.5 years later, after 40% of the subjects had been diagnosed with a psychotic disorder. [ schizophrenia ]
In the patients who later developed psychosis, increased glutamate activityin the hippocampus [ CA1 ] was associated - preceded - with some hippocampal abnormalities [ shrinkage ]during the prodromal phase, but these abnormalities were much more pronounced following the diagnosis.

In addition, the degree of hippocampal abnormality during the prodromal phase could be used to predict the amount of time before a patient developed psychosis.

Excess glutamine activity precedes, drives hippocampal hypermetabolism; the presence of hypermetabolism matched the shrinkage in hippocampus volume.
Taken together, the findings strongly suggest that increased glutamate activity can be an early warning sign for hippocampal dysfunction that will progress during the transition from prodromal to full-blown psychosis [ schizophrenia ] .

Schobel say it is the glutamate hyperactivity - it is the first measurable finding - that goes 'wrong' first - that drives hippocampal reduction - shrinkage - but surely hippocampal new cell reduction would set off glutamate rise, before any size change in the hippocampus. targeting of the CA1 sub- field of the hippocampus by schizophrenia and related psychotic disorders.
8.

Teng KY et al early lesion: late effect Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.

Animals with a neonatal ventral hippocampal lesion (NVHL) develop abnormal behaviors during or after adolescence,
suggesting that early insults can have delayed consequences.
8b.
Lecourtier
Intact neurobehavioral development but dramatic impairments of procedural-like memory following Neonatal Ventral Hippocampal Lesion [ NVHL ] in rats.
early hippo rat lesion gives late adolescent memory problem



How may hippocampal neurogenesis come about ?

Adolescence is a time when there can be stress - leaving family support. They often leave their environments, leave friendships, leave a routine developed in the protected environment of home.
9.
Stress reduces hippocampal new cell proliferation. Stress reduces hippocampal new cell proliferation.

the hippocampal dentate gyrus is in the uncus area of the temporal lobe - vulnerable to herniation pressure if brain swelling pushes the uncus through the tentorial tenting between the cerebral cortex, the certebellum an the mid brain.
Trauma and anoxia during human birth
Or maybe immune reaction to an infection at some crucial time in pregnancy interfere withthe way to new cell proliferation. No direct evidence but ....

November 2016
10.
ED:- Is this adolescent pruning?
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.



10.

Dopamine Hypothesis
egerton pre episode dopamine increase



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