The of schizophrenia has remained leading into early

 

The world shuns those who are labelled
abnormal. Once an individual is diagnosed with any kind of psychological state,
their life and their loved one’s lives are forever changed. somebody that has
schizophrenic disorder suffers in several areas of their life; but, the medical
and psychological communities are fighting for the understanding and freedom
for all that are concerned. The subsequent essay is a brief over read of the Psychotic disorder schizophrenic
disorder, the way the disorder affects people who suffer, and therefore the
research that continues to fight for a cure.

Schizophrenia
is classed as a multidimensional disease with symptoms and impairments that
transcend psychopathy (lunacy). A core feature of schizophrenic
disorder is psychological feature disfunction and it’s
evident at the onset of the disease and persists through the course of the
disease. cognitive functioning ranges from moderately to severely impaired
patients with schizophrenic disorder. The profile of impairment in
schizophrenic disorder involves several of the foremost essential phases of
cognition in humans: memory, attention, reasoning, and speed process. The
extensiveness of this impairment has headed some to conclude that it’s a
disease with a worldwide profile of neuropsychological impairment.

The
whole idea of Hebephrenia, Catatonia and Paranoia into a one disorder known
as ‘Dementia praecox’ was put together by a German Psychiatrist Emil Kraepelin in 1896. Kraepelin believed
that this was a progressive disorder which began at young age and early
adulthood, It showed symptoms of delusions, hallucinations, disorderly thought,
loss of concern in the outside world and loss of emotional reactions.

In
comparison, in 1911 Eugan Bleuler a Swiss psychiatrist, proposed that there was
not a single illness ‘dementia praecox’ but rather a ‘group of schizophrenias’
meaning ‘split mind’ and he also classified the symptoms as primary and
secondary for this disorder. Primary symptoms which he suggested was
ambivalence, autism, loss of interest in the outside world, loss of emotional
responses and altered associations. He felt the secondary symptoms were
delusions and hallucinations which were not specific to schizophrenia.

In
1950, Kurt Schneider also a German psychiatrist made a substantial succeeding
attempt to clarify the clinical meaning of Schizophrenia. He considered certain
symptoms as particularly indicative of the disorder with examples as certain
types of hearing hallucinations and characterised these as ‘first rank
examples’. This idea of schizophrenia has remained leading into early 21st
century. Today the world sides with Bleuler’s affirmation that the disorder
doesn’t always lead to progressively weak functioning, but Kraepelin’s
definition of symptoms and causes is still leaned on.

Schizophrenia is
a disorder which affects the brain and it reflects negatively in the way a
person thinks, acts and sees the world. People with schizophrenia have a
different perception of reality. They often hear voices and see things which do
not exist. They also speak very strange and confusing ways and often think that
others are trying to hurt them or could feel that they are being watched
constantly. With a very unclear line between imaginary
and reality, schizophrenia makes it challenging/frightening to negotiate the
happenings of everyday life. People may withdraw from the outside world or act
out in confusion & panic.

Large
percentage of schizophrenia cases appear in the late teens or early adulthood.
Seldom schizophrenia can even affect young children and teenagers. Although the
signs are slightly different. Generally, the earlier schizophrenia develops the
more severe it is. It also shows to be more severe in men as compared to women.
Schizophrenia can consist of positive or
negative symptoms. The symptoms are classified into 5 categories:

1.     
Delusions:
is a belief held with conviction, even though it is based on a mistaken,
strange and unrealistic view. It could affect the way an individual behaves.
Delusions begin suddenly and could progress over time. People who experience
this often find different meanings in everyday events, an example of this would
be that they might believe people on TV are communicating messages to them
alone or think that there is some hidden in the colours of cars passing on the
street.

2.     
Hallucinations:
Hallucinations are where someone sees, hears,
smells, tastes or feels things that don’t exist outside their mind.
Hallucinations are very real to the individual who is experiencing them, even
though people around them can’t hear the voices or experience the
sensations.

3.     
Confused
speech: People experiencing the condition frequently find
it hard keeping track of their thoughts and conversations. Some people
find it difficult to concentrate and can drift from one plan to another. They may
even have trouble reading there newspaper or watching the TV .

4.     
Disorganized
behaviour: A person’s behaviour may become more
disorganised and unpredictable, and their appearance or dress may seem unusual
to others. People with schizophrenia disorder could behave inappropriately or
become extremely agitated. Some people describe their thoughts as being
controlled by someone else, that their thoughts are not their own, or that
thoughts have been planted in their mind by someone else.

5.     
Negative
symptoms: usually seem many years before someone experiences
their first acute schizophrenic episode. These initial negative symptoms are
typically stated as the prodromal period of schizophrenic psychosis. Symptoms
throughout the prodromal period sometimes seem gradually and slowly worsen.
They include the person changing into more socially withdrawn and progressively
not caring regarding his or her appearance and personal hygiene. Generally, It
may be tough to tell whether or not the symptoms are a part of the development
of schizophrenic disorder or caused by something else.

However, the signs and symptoms depend on
person to person, both in severity and form. Not every person will show all the
symptoms and possibly the symptoms could also change over time.

The
main causes of schizophrenia are not known, but research shows that
schizophrenia usually results from multiple communications between genetic,
environmental, physical and psychological factors can make a person more likely
to develop the condition. A strong component of schizophrenia is its genetic
aspect. There is a 10% change of individual developing the condition if they
have first degree relatives having the disorder. Furthermore, who are
genetically predisposed to schizophrenia will not always develop the disease.
Research on twins suggests that a person’s vulnerability to schizophrenia is a
result of inherited genes then environmental facts act on this to trigger the
disorder. As for the environmental factors involved, a study is directing to
stress either during pregnancy or a later stage of growth. Increased stress is
believed to initiate the condition by increasing the body’s production of the
hormone cortisol.

The
effects can be extremely hard on both the person with the disorder and for
those people who are around them when the signs and symptoms of schizophrenia
are ignored or not treated well.

Schizophrenia is usually treated with an individually
tailored combination of therapy and medication. There are medications knows as
‘antipsychotics’ which can help in reducing the magnitude of psychotic symptoms.
They work by blocking the effect of dopamine chemical on the brain. Antipsychotics can reduce the feelings of anxiety or
aggression within a few hours of use, but may take several days or weeks
to reduce other symptoms, such as hallucinations or delusional thoughts. These
medications are wifely prescribed solely or with combination of other
psychiatric medications. Examples of such
antipsychotics are Chlorpromazine (Largactil
or Thorazine), Olanzapine (Zyperexa), Risperidone (Risperdal), Ziprasidone
(Geodon) and Aripiprazole (Abilify). These are examples of newer versions which
are often referred as second-generation antipsychotics which can work quickly
in comparison to other medication. You may only
need antipsychotics until your acute schizophrenic episode has passed.

Furthermore,
besides the medication, psychological interventions are also important in
treating schizophrenia. These interventions include family psycho-education,
assertive community treatment, substance abuse treatment, social skills
training, supported employment, cognitive behavioural therapy and weight
management. These interventions are important to avoid the risk of patient
defaulting medication especially because of the side effects.

The most dominant idea in the past
and currently is that the dopamine system significantly accounted for the
symptoms present in the patients by the activation of dopamine receptors.
Therefore, the biological approach to treating the symptoms consisted of drug
therapy using the drug that targets to block those dopamine receptors.

However, drug therapy using these
typical antipsychotics is seen as effective in treating the positive symptoms
(any change in behaviour or thoughts, such as hallucinations or delusions),
while having a limited effect on the negative symptoms (a withdrawal or lack of
function that you would not usually expect to see in a healthy person; for
example, people with schizophrenia often appear emotionless and flat) (Chavez
et a..2009). some antipsychotics cause side effects such as tardive dyskinesia,
extrapyramidal symptoms, rigidity and restless. These occur because of blocking
the D2 receptors (Remington, 2003; Horachek et al., 2006). Though, atypical
antipsychotic drugs given in clinically effective quantities do not bring about
these clinical side effects (Leucht et al., 1999; Seeman, 2002) as they are
thought not to act directly on the dopamine receptors in the striatum.

Research has shown that atypical
are better for negative and symptoms, cognitive dysfunction and aggression
(Remington, 2003). The reason behind this is that clozapine and amisylpride
have lower affinities for D2 receptors and only bind loosely to the receptor
which is rapidly released (Horachek et al., 2006; Seeman, 2002), the typical
antipsychotics such as chlorpromazine and haloperidol.

Additionally,
it’s well-known that clinically effective dosages of antipsychotic agent occupy
between 60 to 80 % of brain D2 receptors in patient. However, Clozapine and
Quetiapine solely occupy between 0 and 50% of brain dopamine D2 receptors
(Seeman, 2002). Research currently recommend that because of the atypical
antipsychotics occupying many different types of receptors, symptoms caused by
schizophrenia could be a lot more advanced than an overactive dopamine system
which D2 receptors aren’t the most important antipsychotic drug target in
schizophrenia. However, it may be argued that Clozapine and Quetiapine work
better with fewer side effects because they quickly dissociate from the
dopamine D2 receptors than typical antipsychotics. Recently it’s been advised
that Clozapine could exert an additional direct interaction with NMDA receptors
than different antipsychotic drugs (Chavez et al., 2009; Krystal et al., 1994).
Furthermore, studies have shown that clozapine acts as partial agonists at the
glycine modulating site of the NMDA receptor, at low concentration and it’ll
increase neuronal depolarization and at high concentrations, it inhibits
depolarization that explains why clozapine works better than typical
antipsychotics.

Current
antipsychotic drugs affect glutamatergic activity as well, such as enhancing
release of glutamate in the striatum, changing glutamate receptor density and
directly interacting with NMDA receptors. Most of these effects vary between
the drugs. New clinical trials have been conducted in which NMDA receptors
activity is improved by drugs acting at glycine modulatory site of NMDA
receptors have decreased in negative symptoms and improvement in patient’s
cognitive function (Goff and Coyle, 2001).

Some
research has shown that effects of certain atypical antipsychotics on the NMDA
receptors could tell between these drugs from typical antipsychotics are the
reason they work better on schizophrenic patients in treating them. It is found
that haloperidol which possibly could be a typical antipsychotic did not act
with NMDA receptors at clinically relevant concentrations, though that
clozapine did displace the ligand from NMDA receptors at therapeutic levels.
This shows that modulation at the NMDA receptors could also be a far better
therapeutic target.

Glutamatergic
neurons are a major pathway linking the limbic system, cortex and thalamus.
These regions have been drawn in schizophrenia. Therefore, the idea that
glutamate system is a great way to treat schizophrenia. Schizophrenia is a
result of diminished activation of NMDA receptors in the brain than overactive
dopamine system. This Pharmacological evidence was supported by phencyclidine
(PCP), ketamine and other NMDA R antagonists blocks the NMDA receptors so in
healthy volunteers produce symptoms and cognitive impairments close to
schizophrenia (Krystal et al., 1994; Hashimoto et al., 2003), and it increases
dopamine release in the mesolimbic system (Goff and Coyle, 2001). NMDA receptor
antagonist induced psychosis models: Cognitive deficits and negative symptoms
better than dopamine model (Krystal et al., 1994; Hashimoto et al., 2003), so
the action of NMDA is a hopeful treatment when it comes to schizophrenia. In therapeutic trials, drugs
that indirectly improve NMDA receptors have been shown to reduce negative
symptoms and instead improve cognitive functioning in patients. Moreover, in
clinical trials in which the drugs that enhance NMDA receptors activity have
shown to improve symptoms in schizophrenic patients (Goff and Coyle, 2001).
Experiments have been carried out on partial agonist such as glycine, D-serine
and sarcosine (Kantrowitz and Javitt, 2010).

Also
in the case of haloperidol, synaptic plasticity has been well documented in the
striatum, where the highest concertation of D2 receptors is present (Horachek
et al, 2006). Although still some studies show that by blocking D2 receptors in
the stratum does not reduce the symptoms of working memory impairments. Hence,
it has been advised that direct modulation of hyperactive NMDA receptors by drugs
like Acamprosate
can allow us to target microcircuits within
the mesocratic,
which are not accessible to conventional D2 based treatments to help
schizophrenia (paz et al, 2008).

As
PCP encourages a lot of symptoms in humans akin to those seen in the condition,
it has been used to attempt to produce a pharmacological rodent model of
schizophrenia. Acute PCP management makes hyperlocomotion, social withdrawal
and impairment of both PPI and cognition in rodents.

Since it’s
not possible to perform controlled chronic PCP studies in humans, it has been
reported that recreational abuse of PCP produces symptoms that persist beyond the
end of treatment (Rainey and Crowder, 1975).

Additionally,
early PET scans show that PCP abuse was accompanied by deficits in the temporal
and frontal lobes, which matches the changes seen in schizophrenic patients
(Hertzman). This has been on the basis of evaluating of the effects of chronic
PCP in rodents, most commonly using twice daily administration for 7 days
followed by a 7-day washout period before the start of an experiment described
as subchronic.

Minocycline is
another drug which have been tested in order to see if it has any possible
effects in treating symptoms of schizophrenia. although the exact mechanism of
action of minocycline remains vague, the recent research conducted with
minocycline suggest that it doesn’t modulate the glutamatergic system. In animal studies, minocycline reversed several
NMDA – R transmission.

 

Some recent
work with an ampakine also show that positive modulation of the AMPA receptors
may also provide another glutamatergic approach to treat cognitive deficits in
schizophrenia (Goff and Coyle, 2001).

Even though
the conclusions are preliminary, it is suggested that dysfunction of
glutamatergic neurotransmission plays a significant part in treating the,
especially  the negative symptoms and
cognitive impairments and it is a promising target for drug development (Goff
and Coyle, 2001). Researchers have considered developing drugs that restore the
hyper glutamatergic state by regulating the abnormal NMDA function without
changing the balance of synaptic and extrasynaptic glutamatergic transmission
has been found to be useful for schizophrenic patients.