Ram Sharma: an Indian business man, leaving his business, to run a national programme for his country
Where a method of help exists that brings benefit, there is a service NEED for it.
A NEED is defined as the ability to benefit from a particular kind of intervention.
If a method of care help exists that brings benefit to disability , either for amelioration, or prevention of disability, any individual in the particular disability is in NEED of that intervention.
The fact that a person in the care situation has acquiesced, has so far gone on without the need, does not overrule the NEED.
Because a benefit is not offered, that is not to say it is not available.
Because a benefit is not offered, that is not to say that the care situation cannot, and does not, NEED it.
A NEED unmet is a Service deficiency
NHS staff have a Form they have a duty to fill out that informs management when their Service is deficient, missing a service that can be made available, is required, that is not being delivered.
Their patients have
The abnormality in schizophrenia
Working memory capacity is the maximum number of items that we can transiently store in working memory. It is a good predictor of our general cognitive abilities.
Working Memory Capacity is what makes available sufficient experience from store at the right time, in the right place, on the right occasion, to complete any sequence in behaviour management that takes to completion what you want to do.Working memory capacity [ WMC ] , at a level that is necessary for the requirements of ordinary daily living, is insufficient in continuing schizophrenia, to meet ordinary living demands.
The effect of reduction in capacity [ WMC ] is worst the earlier the illness strikes, because thenceforward not much is added to whatever experience they have stored before that time.
The Evidence for the Abnormality
New cell formation [ neurogenesis ] in the hippocampus area of the brain, is the key to memory management. It is used for the selection of material - seen - heard - felt - that it is important to store away for what may be useful later.
It is wanted for suppressing those things perceived that are not to be let in.
It is part of the network for retrieving from any past experience what is needed now.The evidence that reduced hippocampal neurogenesis is implicated in the reduced Working Memory Capacity in schizophrenia comes from two sources.
1.
In field surveys[ Kelly et al ; Al-Usri et al ]
They found general memory failure in people with continuing schizophrenia in the community ...
2.
academic research in the 'laboratory;
[ References Academic references: links to online papers. ]Academic study [ Siebzehnrubl ] confirms in humans - what was well studied and accepted in rodents - neurogenesis in the hippocampus correlates with memory status.
If new cell formation in the hippocampal area of the brain is reduced, there is poor memory. Intact neurogeneis means intact memory.Another academic study [ Reif ] in banked postmortem material from people with continuing schizophrenia found reduced neurogenesis in their hippocampus.
If this is a general finding in schizophrenia memory disability will be a general problem in the illness
Confirmation that hippocampus new cell formation in schizophrenia is reduced and affects performance comes 'laboratory' studies.
Testing in the laboratory for registering information [ Gold ] finds reduced memory capacity - less information is taken in and held onto - in schizophrenia subjects compared with a control sample in people unaffected.
" Patients show clear reductions in the number of items that can be stored in WM [ Ed Working Memory ] but no evidence that their [ those that are stored ] WM representations are less precise or less stable than those of healthy individuals "This study [ Raalten ] agrees that capacity is less, less able to deal with more complicated matters.
But a simplified well rehearsed test could be stored away freeing up working memory . But this does not allow effective storing of information when something else has to be attended to at the same time - the more usual situation. There is not enough holding information capacity for that.
The Remedy for the DisabilityThe remedy takes account of the Raalten study [ ... rehearsal at a simplified level to start with enables a sufferer to take on more and more .... Raalten ] Although subjects failed on the more distracting situations, they succeeded when helped by starting at a simplified level, rehearsing that till established , adding to it in the same simplified steps. The problem for a service is to pitch the entry difficulty at a level and at an attraction that eases and captures engagement.
A simplified introduction will be something like this description of a cognitive remediation programme, [ Cognitive therapy ]eventually leading to a programme of activities within the week, in settings with appropriate allowance of time to rehearse , introduced and accompanied into the setting by familiar mentors, by family or by community support workers with the backing authority of the Mental Health Trust Team, a daily and weekly routine can be arrived at and stored away, as something to be attended to in the coming days and week.Clearly if you have lost working memory capacity at seventeen, a loss that continues, that is a different matter from if the loss kicks in at thirty-five.
When the illness arrives in adolescence and early adulthood there is incomplete experience.
Reduced working memory capacity will prevent them ever achieving an ongoing daily and weekly routine for themselves that is sustaining, as such a routine at work is normal for others.
Those where the illness is late arriving have already built up skills and routines in personal, domestic, relationship and work situations.The shortfall in working memory disrupts prospective memory - the memory store dealing with the consequences as an intention goes forward - means that a helpful routine cannot be put in place by those with continuing schizophrenia - by themselves. Seeing a future goal, holding on to it, and meeting its associated requirements is not possible with the capacity in working memory capacity so reduced.
The routine once well established has built a matching coherent internal system to go to , an expectation pointing towards a definite future in the real world, rather than falling back when in 'default' consciousness, [ doing nothing and going into 'mind wandering' ] , into the illness, driven by the preserved, seemingly coherent, system of misbeliefs.
These weekly activities give regular 'breaks in the week' for the community and family carers reducing the opportunity for the inevitable, inescapable high emotional expressions persisting in any one place, that can precipitate breakdown.Regular outside activities in the week, obtained by preparatory mentoring, appropriate for the level of personal skills, personal experience, personal interests will maintain a routine that helps both sufferers and family carers to achieve some life of their own.
Whatever is required to provide this: cajoling, persuading, professional relationship presuming consent, coercing: the best interests of the patient require this engagement.Their family carers need these breaks.
If not achieved, it means there remains a service deficiency, a clinical need unmet, to be registered on the Service Deficiency Form by Staff, with the Mental Health Trust doing the service delivery.
References : -
Clinical Surveys
1.
Measuring memory impairment in community-based patients with schizophrenia
Al-usri, J. Bruce, MBChB, MRCPsych, S. Frost, MBBS, MRCPsych and D. Mackintosh, MBChB, MRCPsych
B J PSYCHIATRY 2006 189 132-132.
Cognitive function in a catchment - area - based population of patients with schizophrenia
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
Academic Research3.
Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies
F.Siebzehnrubl and Ingmar Blumcke Epilepsia, 49(Suppl. 5):5565, 2008
hippocampal neurogenesis
Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans
Roland Coras,,* Florian A. Siebzehnrubl,,* Elisabeth Pauli,,* Hagen B. Huttner, Njunting,et al
Brain 2010: 133; 33593372
4. 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, 514522
Reif et al 2006the most important finding - never reproduced [ subsequent links give confirmation, ] as does the inability of sufferers to accumulate maturing experience after the illness- they stick in the area of interest and level of personal domestic and social competence they had before the illness- their friends and family move ahead and away, they are left behind.
3.
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): 570577.
link to the Gold et al paper
4.
Automatization and working memory capacity in schizophrenia
Tamar R. van Raalten , Nick F. Ramsey , J. Martijn Jansma , Gerry Jager a, Renι S. Kahn / Schizophrenia Research 100 (2008) 161171
RaaltenThis study now confirmed :-
4a.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
4b.
Brita Elvevaag, Elizabeth A Maylor, Abigail L Gilbert
Habitual prospective memory in schizophrenia
[ BMC Psychiatry 2003.3.0 research article open access ]5.
targeting of the CA1 sub- field of the hippocampus by schizophrenia and related psychotic disorders.
Scott A. Schobel; Nicole M. Lewandowski; Cheryl M. Corcoran; Holly Moore;
September Archives of General Psychiatry, 2009
hippocampal change preceding and bringing on schizophreniasome confirmation in this paper ...
5a.Mecheli et al
Archives General Psychiatry 2011 May;68(5):489-95.
Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study.
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A correspondence is found between the level of hippocampal neurogenesis cells and the level of effective working memory.
Siebzehnrubl et al [ Epilepsia 49 (suppl 5) 55-65 2008 ]
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.
2.
Reif et al 2006
This study is on post-mortem material held ' in stock ' much earlier.
The hippocampal area in tissue from schizophrenia is compared with that from mood disordered people and normal controls.Quote " Does the finding of decreased Adult Neurogenesis [ AN ] in Schizophrenia make sense?
Sz is known to go along with several cognitive deficits, which is stable over time, that is, trait rather than state dependent.
The prime role of hippocampus is rather memory formation than affect regulation.
Thus, diminished Adult neurogenesis, which has been suggested to result in impaired memory formation, will contribute to the cognitive impairment seen in Sz; improvement of cognitive functioning in Sz by clozapine might be due to the increase of AN seen in animal studies.
As learning, exercise, and enriched environment all increase AN as well, this directly points toward non-pharmacological treatment of schizophrenics. The preliminary finding of reduced AN in Sz provided in the present study is thus worth being pursued further."3.
Gold paper :- link Gold et al paper
Sufferers from persistent steadied schizophrenia on standard medication were asked to recognise and place colour worded items, declaring them at one second and four seconds after exposure
What was examined was the number of items :-
accurately stored
retained to be able to show them at 4 secs.
Schizophrenia subjects were as accurate as controls, but, they did not hold on to the items at 4 secs.
The situation at delay showed no deterioration of capacity nor of precision.
They held what was stored. They did not store all at first point.
The problem is in the use of the initial storage capacity.
They recognise the placement and the number at 1 second .
They fail to show them at 4secs.The failure is in the capacity to accept, so that they cannot keep them where they could be drawn on later.
' Visual WM representations are neither less precise nor more prone to decay in schizophrenia.Instead, patients exhibit a reduction in the number of items they can concurrently maintain in WM '.
... quote ... " Patients show clear reductions in the number of items that can be stored in WM [ Ed Working Memory ] but no evidence that their WM representations are less precise or less stable than those of healthy individuals "4.
[ Raalten... but if not, link to a bigger journalist summary ] points to a remedy.
van Raalten and colleagues found that, although the patients' learning ability was impaired when frequent information updating was required,
their capability to profit from practice under stable learning conditions was unimpaired.
" When encouraged and accompanied, given the opportunity to practice,
Sufferers do store what they have memorised: equally as well as for 'control subjects', by 'chunking'.
So, that is,
This 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) is largely preserved.
Here, patients showed significant performance improvements and significantly reduced WM activity with increasingly successful processing.5.
This study points to hippocampal change preceding and bringing on schizophrenia [ Schobel et al:- In the September Archives of General Psychiatry, 2009 ] was on 18 'prodroma subjects who met clinical criteria for being at ultra high risk of developing psychosis.
These subjects presented symptoms that did not quite rise to the level seen in psychosis.
For example, prodromal subjects might profess unusual ideas that seem less compelling than delusions.During the two years of follow-up, seven of the prodromal subjects became psychotic.
Of the three dysfunctional areas seen in subjects with more established disease, only the CA1 subfield in the hippocampus appeared awry in these subjects.
Notably, high activity in this area predicted the eventual emergence of psychosis.
In fact, it did so with a positive predictive value of 71 percent and a negative predictive value of 82 percent.
Now confirmation from a multi site study .
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 crucial to the expression of illness.
Tamminga : hippocampus/schizophrenia review
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.7.
Nature August 2011 Volume: 476, Pages: 458461 Jason S. Snyder et al
Snyder
Never mind the puff for depressive ilness - the mice equivalent doesn't stand up......... ' The hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis'
A possible future remedy ? A bit technical !!
Pieper[They have patents for all the molecules that may have been productive- july 2011 ]
Cell 142 39-51 July 2010
new on protogenes
*** New !!! add this to the above protogenic repair
Ramamoorthi K, Fropf R, Belfort GM, Fitzmaurice HL, McKinney RM, Neve RL, Otto T, Lin Y. Npas4 regulates a transcriptional program in CA3 required for contextual memory formation. Science. 2011 Dec 23; 334(6063):1669-75.
More productive studying ?
There are developments now in new techniques to study the level of neurogenesis activity in the living ....
Manganas:- Science 318 980-985 2007
" In our work, we identified a spectroscopic biomarker of NPCs,
developed a methodology to detect this biomarker in the live brain,
and demonstrated the use of the biomarker for identifying NPCs [ Neural Precursor Cells = maturing to stem cells ] in the live human brain.The NPC biomarker could be readily detected in vitro with 1H-NMR,
but its detection at low concentrations in the live brain with 1H-MRS
required the development of more refined methodology.Our SVD-based signal processing proved to be superior to the traditionally used Fourier transform
and can now be applied in a variety of imaging settings where low levels of a particular metabolite preclude its reliable detection in vivo.Our results suggest that the NPC biomarker, represented by a 1.28-ppm spectral peak, is a complex mixture of saturated and/or monounsaturated fatty acids and related compounds.
The functional relevance of these molecules for the control of proliferation and differentiation of NPCs remains to be elucidated.
Finally, our data on humans provide in vivo imaging evidence for NPCs in the human hippocampus.
These findings support the numerous data demonstrating continuous neurogenesis in the dentate gyrus .
We also demonstrated that in humans the presence of the NPC biomarker in the hippocampus dramatically decreases with age.
Although a decrease in neurogenesis has been reported in aging mammals,
these are the first data from the living human brain that indicate a decrease in NPCs during brain development from childhood to adulthood.
A shame the study did not record results in the age range 17- 24
- reckoned to be the highest level for adult neurogenesis ,and a critical age for starting schizophrenia.
The normal age range for this period will be necessary for any before/after neurogenesis change in schizophrenia.
More generally, this biomarker can be applied to track and analyze endogenous or transplanted NPCs,
to monitor neurogenesis in a wide range of human neurological and psychiatric disorders,
and to evaluate the efficiency of therapeutic interventions. "
Ana C. Pereira et al PNAS March 27, 2007 vol. 104 no. 13 5643
With continued debate over the functional significance of adult neurogenesis,
identifying an in vivo correlate of neurogenesis has become an important goal.Here we rely on the coupling between neurogenesis and angiogenesis
and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis.First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice.
Among all hippocampal subregions, exercise was found to have
a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis.
Moreover, exercise-induced increases in dentate gyrus CBV
were found to correlate with postmortem measurements of neurogenesis.Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans.
As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function.Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis
and that exercise differentially targets the dentate gyrus,
a hippocampal subregion important for memory and implicated in cognitive aging..