Further notes i made on the brain & Schizophrenia/Mental Illness ;)))

There is also ongoing cortical pruning that produces through childhood and is
more or less complete by adult....... Essentially the brain is organized to
filter and unify sensory information so that a coherent response can be made,
ensuring survival (pp.17)..The prefrontal cortex appears to be associated with
emotional aspects of behaviour and the inhibition of inappropriate behaviour.
The prefrontal cortex also plays an important role in shaping the temporal flow
of information..Thus, the prefrontal cortex not only holds information on-line
in working memory but also shapes the temporal sequence of response.



The temporal lobe also includes the hippocampus and amygdale...The amygdale is
closely connected with other cortical regions, particularly the obitofrontal
cortex. It facilitates emotional memories and fear conditioning...Both the
hippocampus and amygdale are older parts of the brain, seen in all mammals.
These brain regions have three layers, in contrast to the six layers seen in
other parts of the cortex involved in processing multiple sensations, referred
to as heteromodal cortex. A structure closely related but generally considered
to be separate from the four main lobes of the hemisphere is the insula, which
lies between the stiatum and the temporal lobe along the lateral fissure. The
insula is closely connected to parts of the brain that monitor "internal states"
of the body. It is also important in speech articulation and pain perception and
is often activated when subjects are asked to produce well-learned category
knowledge (Martin et. Al., 1996) - (p.20).



Interesting comment - Schizophrenic patients often show a variety of social and
intellectual deficits in childhood prior to the onset of the
disorder....Scholastically non significantly below average in primary grades,
but drop significantly between the ages of 13 and 16 (puberty where the child
attempts to gain self control - power struggle stage) - but is it as suggested "
perhaps as a precursor to the cognitive impairment seen early in the illness" -
or merely the result of a reluctance to struggle in power struggles?
...."Interestingly, the strongest predictors for the development of
schizophrenia were deficits in social and intellectual functioning and in
organizational skills (Davidson et al., 199a). (p.31). See suggested
deficits before the onset of psychotic symptoms i.e. children manifested
atypical emotional expressions and movements (already withdrawn?) - see p.30-1.
Genetic studies have failed to show a genetic link to schizophrenia.."making the
task finding the gene more difficult is the fact that carriers of genes involved
in schizophrenia do not necessarily express the disease, but have (what is
perceived to be) abnormal behaviours or psychobiological markers related to
schizophrenia, such as abnormal eye tracking (eye tracking?) (p.37)
....Genetic linkage- Early studies failed to find direct links to D2 receptor
abnormalities (p.46).



The post-mortem studies would seem to suggest that there are glutamatergic
abnormalities in schizophrenia, but paradoxically both increases and decreases
can be seen Most of the evidence for increased glutamatergic receptors comes
from the anterior cingulated and prefrontal/orbitofrontal regions, whereas
deficits are seen in most glutamatergic receptor types in the hippocampal and
temporal regions. This pattern would seem to argue against a generalized loss of
glutamatergic synapses but could be in keeping with abnormal glutamatergic
activity and/or a loss of synapses in specific neuronal circuits. (p.50).



One could say that the findings from neuropsychological studies are both
encouraging and discouraging. Discouraging because no finding differentiates all
patients from controls, and what findings there are do not seem to be specific
to schizophrenia. There are abnormalities in a number of brain regions - the
frontal, temporal and basal ganlia regions being more common than others" and
many " of the abnormalities found are related to known functions of these areas
- executive function, verbal fluency, memory, and encoding, among others", but
"none of these regions could account for these abnormalities in isolation. They
are linked in functional neuronal circuits that appear to be damaged in some
way, but what and where is the damage? .. Neuropsychological tests do not allow
us to look into the brain, but brain imaging techniques do (p.74).



The findings of brain imaging tests - the model is consistent with the effects
of stress in schizophrenic patients. Either increased or decreased dopamine
could depress emotional processing centres. However, the prediction is
counterintuitive......Diminished drive representation in the amygdale may be one
of the causes of close connections between these brain regions. Deficits in
attention and the PET studies showing aberrant emotional processing in
schizophrenic patients fit well with the model. However, there is little
evidence directly implicating either the orbital prefrontal cortex or the
amygdale beyond this , and it would be difficult for this model to account for
changes in other parts of the brain such as the cerebellum (p.140).



Patients discharged home to emotionally over involved and critical families are
more likely to relapse. Stress must therefore play a role in the illness. While
several investigators have explored how this might be manifested in
abnormalities in the response to stress in schizophrenic patients (Deutch, 1993;
Laruelle, 200; Moghaddam 2002,) the most comprehensive model has been proposed
by Lieberman et al (1997).



Lieberman et al (1997) point out that psychostimulants can produce psychotic
symptoms in healthy individuals and at low doses exacerbate psychotic symptoms
in schizophrenic patients. Stimulant abusers after recovery from
stimulant-induced psychosis exhibit a lower threshold for the induction of
psychotic symptoms when re-exposed to stimulants. This observation suggests that
schizophrenic patients may develop sensitization to dopamine in much the same
way that stimulant abusers or rats develop it when repeatedly exposed to
amphetamine (pp.150-1).



Manic-depressive psychoses from dementia praecox - patients with mood disorders
have different symptoms..suffer from overwhelming depression lasting months or
years, interspersed with periods of extreme mood elevation and euphoria..they
patients sometimes have psychotic symptoms, the symptoms are usually
mood-congruent and patients recover to a large degree between
episodes...Mood-disorder patients can have enlarged ventricles but do not
usually demonstrate generalized loss of grey matter (p.152).



The understanding of neuronal circuitry of mood disorders is no further along
than that of schizophrenics, but even at this level of knowledge there are
important differences. The orbitofrontal and subgenual prefrontal cortices as
well as the amygdale are most likely to be involved...these are the parts of the
brain involved in emotional processing. There is some overlap with schizophrenia
in the dorsolateral prefrontal cortex and hippocampus, but structures such as
the nucleus accumbens and thalamus are less likely to be involved, perhaps
suggesting that mood disorders are less likely to be associated with anomalies
of perceptual and cognitive integration. This is consistent with the clinical
picture of mood disorders, which is rarely associated with disturbances in the
sense of self or perceptual disturbances (p.154).



Schizophrenics have dopaminegic hyperresponsivity (E. also look at dopamine in
relation to love, flight and fight, natural responses). Schizophrenic patients
have difficulty monitoring and willing action and are vulnerable to stress and
although the patterns may vary from patient to patient, we have a fairly good
ides of what parts of the brain are affected. Not all would agree that there are
progressive changes in schizophrenia, but the data for progressive volumetric
loss in a substantial number of patients is convincing.



Schizophrenia begins begins long before the onset of the characteristic
symptoms. An early neurodevelopmental origin seems the most likely from evidence
of abnormal cell migration in post-mortem studies, the association with
obstetric and perinatal complications or stress and the many behavioural and
soft neurological signs that patients show before the onset of the illness.
However, there is no clear understanding of which structures might be affected
(p.156). .......



All of the drugs we use to treat schizophrenia affect D2 receptors and
dopaminergic agonists can produce hallucinations and delusions like those seen
in schizophrenic patients (p.157).......



Dopamine is involved in the stress response and we do know that schizophrenic
patients tend to relapse under stress (p.157). In the dopamine sensitization
model, deficits in multiple control dopamine mechanisms involving the prefrontal
cortex and temporal lobe structures could lead to dopamine abnormalities,
whereas the imbalanced-brain model is not very sprcific about the way in which
dopamine hyperresponsivity or hyperarousal come about. Schizophrenia follows a
variable course characterized by exacerbations of hallucinations, delusions, or
thought disorder interspersed with periods of relative remission often
associated with some degree of flattened affect and lack of motivation. Although
none of the models fully account for these longitudinal changes, the dopamine
sensitization and im-balanced-brain models at least integrate the effects of
stress on dopamine that could explain some of the variability.....Increased
dopamine activity leads to hallucinations and delusions.....It is likely that
dopamine mediates the salience of environmental events and internal
representations. It has been proposed that delusions may result from the
aberrant assignment of salience to experiencial events, whereas hallucinations
may arise from the aberrant salience of internal representations (Kapur, 2003)
(p.159).



Kind Regards

Elaine












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