Schizophrenia - Essay Discussing the Aspects of it's Pathophysiology, Therapy, Psychosocial and Public Health Issues in Relation to a Clinical Case of Paranoid Schizophrenia

Schizophrenia is a severely debilitating mental health illness which is relatively common in the UK with a prevalence of 7.2/1000. This essay will discuss aspects of its pathophysiology, therapy, psychosocial and public health issues, in relation to a clinical case of paranoid schizophrenia. The focus is the treatment.

A. Case History
A.i. Psychiatric history
Presenting complaint and history of presenting complaint: EM is a 57 year old Spanish male who has a 24 year history of chronic paranoid schizophrenia. He was informally admitted by the crisis resolution team, who were notified of his condition by his visiting son. He was found rapidly pacing his flat in a distressed manner and shaking intermittently due to “painful electric shocks”. He was also experiencing severe headaches and abdominal pain, and was anxious regarding men “spying” on him and “taking pictures”. His pains and anxieties agitated him and caused onset insomnia. He was diagnosed with a relapse of paranoid schizophrenia, believed to be precipitated by a recent change in medication. His condition continued to deteriorate after admission and he becamenon-compliant, so was detained under the Mental Health Act (1983), section 2 (admission to hospital for up to 28 days for assessment and treatment).

Past psychiatric history: In 1986 EM was referred to a psychiatrist, by his GP, who diagnosed him with paranoid schizophrenia. He suffered from delusions of persecution which responded well to treatment. He has been admitted into the psychiatric ward approximately ten times due to acute exacerbations, episodes of post psychotic depression and once due to an attempted suicide where he tried asphyxiation using his car exhaust and overdosed on a variety of pills. His last relapse was 6 years ago; it was brought on by non-compliance with medication and he was admitted under section 2.

Past medical history: EM suffers from type 2 diabetes and hypercholesterolaemia.

Medication: He is currently taking 200 mg Amisulpride twice daily (anti-psychotic), Metformin 500mg quarter daily (anti-diabetic) and Ezetimibe 10mg once daily (anti-hyperlipidaemic).

Family history: EM’s auntie also suffers from paranoid schizophrenia. His father died in 1986 from bowel cancer, and his mother died in 1997 due to a stroke.

Personal history: He is the fifth child of ten and had a normal birth and subsequent development. He lived on a farm with his family in Spain, and they were “very poor but happy”. He had a good relationship with all members of his family, especially his father.

He finished school at 16 and began work; he then left Spain at 19 to live and work in London as a waiter. He got married at 28 and had two children; he then bought a house in the New Forest area where he got a job as a factory worker. His wife divorced him in 1997 due to “unreasonable behaviour” and kept the house and children. EM had a very close relationship with both of his sons and they still visit him on a regular basis.

Social history: EM lost his factory job due to tendonitis preventing him from operating the machinery, and has since done some private Spanish tuition lessons but finds it hard to cope with the stresses of work so has stopped. He receives income support, disability living allowance and housing benefits.

He stopped smoking only a few months before admission but has a 50 pack year history. He is adamant that he rarely ever drank alcohol and has only ever tried cannabis on one occasion in his youth.

Premorbid personality: “A very positive person” who was happily married and had many friends.

Risk assessment: He poses moderate risk to himself due to a history of self neglect, social isolation and three suicide attempts in one day. He has suicidal thoughts but no intentions or plans.

A.ii. Mental state examination (fig 1)

Appearance and behaviour: Mr EM is a tall, stocky man who was dressed casually and appeared well kempt. He was generally calm, only becoming agitated when discussing his delusions, yet was cooperative and maintained good eye contact.

Affect: His affect was objectively euthymic and subjectively 4 out of 10. He showed signs of affective flattening/restrictiveness*

Speech: His speech was of a normal volume, rate and tone.

Thoughts: There were no abnormalities in the form of his thoughts. The content included persecutory delusions, that a group of people are out to get him, seem to underlie all others. He believes the group could be the conservative party as he watched them complain about him on the news, a delusion of reference. He believes they had a chip implanted in his tooth when he went to the dentist for a filling, a delusional perception. Through this chip they cause him the physical pains which are somatic delusions. He believes through this chip they can also stop his thoughts (thought block), made him dream about killing people (thought insertion) and can read his mind (delusions of mind being read).

Perceptions: EM did not experience any hallucinations.

Cognition: EM scored full marks on the mini MSE.

Insight: EM’s insight is moderate, as he realises some of his somatic delusions may be due to “some sort of mental illness”, but still believes firmly in his persecutory delusions.

B. Pathophysiology
Schizophrenia is described as “a disintegration of the process of thinking, of contact with reality and of emotional responsiveness”. Its diagnosis, according to ICD-10, is based on self-reported symptoms, characteristic of schizophrenia, which persist for at least one month. These symptoms can be positive (delusions, hallucinations, thought disorder, catatonic symptoms) or negative (apathy, avolition, alogia, affective incongruity/blunting). EM was diagnosed with paranoid schizophrenia because he displays two characteristic features: paranoid projections (preoccupation with persecutory delusions, delusions of reference and delusions of control) and hostile belligerence (suspicion of people, blaming others for problems and complaining).

B.i. Aetiology
Schizophrenia is believed to be caused by a combination of biological, psychological and social risk factors which interact, producing psychosis when a threshold is crossed. The causal model can be used to divide the aetiological factors into those which predisposed, precipitated and perpetuate EM’s schizophrenia (fig 2). The precipitating and perpetuating factors in EM’s illness are considered in section D as primarily they have a psychosocial basis.

Predisposing factors
The lifetime risk of schizophrenia is approximately 1% in the general population, whereas the concordance rate in monozygotic twins, who are genetically identical, is 40-50%. This highlights the genetic basis, but also shows schizophrenia is not 100% genetic, and so is influenced by the environment. EM’s auntie, a second degree relative, also suffered from paranoid schizophrenia, so the relative risk of EM developing schizophrenia was already 3-6 times higher than the general population. The fact they share the same subtype could be further evidence of a genetic basis as paranoid ideation has been found to run in families. However this also has an environmental aspect as the thought process of the parents influences that of the child. Neurotransmitter theories
Several theories which provide some insight into the pathophysiology of schizophrenia arose from pharmacology. The dopamine hypothesis is the most prominent theory and postulates that delusions are caused by hyperactive dopamine neurotransmission in the mesolimbic tract (fig 4). It developed from a finding in 1951 that chlorpromazine, a dopamine receptor (principally the D2 receptor) antagonist which was being used as a sedative, was able to reduce schizophrenic symptoms rather than just cause sedation. Further support for this hypothesis came from the finding that amphetamines, which cause a massive release of dopamine centrally, produce a psychosis involving visual hallucinations and paranoid ideation. Serotonin hyperactivity is also thought to be involved, this arose from the finding that the hallucinogen, LSD, is a serotonin agonist.

B.iv. Neuropsychiatric models
The salience model explains the relationship between the dopamine hypothesis and the delusions which EM suffers from. This model was derived from the normal role of dopamine in reinforcing behaviour via reward mechanisms and increasing the signal-to-noise ratio, which increases the salience of stimuli associated with reward. The hyperactivity of dopamine is thought to cause an abnormal attachment of salience to external stimuli and internal representations; delusions are then developed by the patient in order to explain the abnormal salience experience.

Another approach is to explain delusions via the anatomical changes that occur. Generally in schizophrenia there is reduced brain weight, reduced brain size (particularly in the frontal and temporal cortices), ventricular enlargement and the loss of cerebral asymmetry. Delusions have been attributed to changes in the entorhinal cortex, a memory centre found in the temporal lobe, which is smaller than in normal subjects yet larger than in deficit schizophrenia. It is thought that an abnormally small parahippocampal gyrus, which plays a role in encoding memories and retrieving them, feeds corrupted information into the entorhinal cortex which holds onto it as a sensory template. The entorhinal cortex then brings up old irrelevant memories, which the hippocampus will retrieve. The amygdala will then add emotional salience to these memories, causing them to become crystallised as delusions.

C. Treatment
C.i. Pharmacological interventions
Antipsychotics are the primary intervention for schizophrenia and are divided into two groups: typical (first generation) and atypical (second generation). The principal difference between them is that atypical antipsychotics are developed with different pharmacological profiles to reduce the incidence of extrapyramidal side effects (EPS). The mainstay of EM’s treatment so far has been antipsychotic drugs, therefore they will be discussed in relatively more depth. The nice guidelines explain that treating patients with antipsychotics should be considered as an “explicit individual therapeutic trial” in order to find the drug best suited to the patient. This approach was taken with EM and the three drugs relevant to his most recent admission are discussed.

Zuclopenthixol Decanoate (ZD) (typical antipsychotic):
Up until three months before admission, EM was having 200mg depot injections of ZD every three weeks for almost six years. Depot injections are large doses of an antipsychotic drug, which have been modified for slow release and were prescribed for EM to prevent non-compliance. The half life of ZD is approximately fourteen days, so the length of time it would take to be eliminated from the system may explain why EM only relapsed three months later. The principle mechanism of ZD is antagonism of the D1 and D2 receptors. The antagonism of the D2 receptors will reduce dopaminergic activity in the mesolimbic system and this, as indicated in the dopamine hypothesis, will alleviate positive symptoms (EM’s delusions). There is some evidence that antagonism of D1 receptors may contribute to antipsychotic activity, but it may be that reducing D1 activity increases negative symptoms, especially disordered cognitive function.

The community mental health nurse’s (CMHN) notes, made during visits to administer depot injections, testify to ZD’s effectiveness. Generally EM’s mental health was good throughout the six year period, he still had some paranoid delusions, only they did not distress him and he was able to do some work as a Spanish tutor. However antipsychotics do not totally prevent the symptoms, they merely dampen down motivational salience through their reduction of dopamine; hence the patient will no longer be concerned with their delusions but they may still exist.

EM experienced extrapyramidal side effects (EPSs) as he complained of tremor in his arms and a restlessness which caused onset insomnia, likely to be akathasia. EPSs occurs due to the antagonism of D2 receptors in the nigrostriatal tract (fig 4) and are a common problem in atypical antipsychotics as while the therapeutic effects begin at 65% D2 receptor occupancy, EPS begins at 78%. The CMHN noted his face had become mask like and his voice flattened, suggesting emotional blunting due to the bloackade of D2 receptors in the mesocortical tract (fig 4). EM described feeling sleepy all the time, indicating sedation due to the histamine receptor bloackade, which was one of his main annoyances with the drug.

ZD is a relatively cheap drug, the net price of 200mg of Clopixol costs £2.21, and considering this will last for three weeks this is only a cost of 11p per day, however the cost of the CMHN visits should also be taken into account.

Aripiprazole (atypical antipsychotic)
Due to the side effects EM experienced with ZD, his medication was changed to oral Aripiprazole (15mg once daily)which has lower EPs and sedation. Aripiprazole functions as a dopamine partial agonist as it stimulates postsynaptic D2 receptors, enhancing dopamine transmission, and presynaptic autoreceptors, reducing dopamine synthesis and release. This mechanism is supposed to decrease dopaminergic transmission in hyperdopaminergic areas to reduce positive symptoms, and the opposite in hypodopaminergic areas. It was ineffective in controlling EM’s symptoms as he suffered a relapse while taking it and despite increasing the doage after admission his mental health continued to deteriorate. Switching antipsychotics drugs can be difficult and risky, especially since it was from a dopamine antagonist to partial agonist, and sedating to non-sedating. In his recent relapse his delusions were the same as previous with a few additions, supporting the theory that the patients delusion were not eradicated, they simply remained dormant, and stopping medication will allow the resurgence of a heightened dopaminergic state, allowing the dormant symptoms to be reinvigorated with salience.

The net price of a 15mg 28 tablet pack of Ablify tablets will cost £97.67, a cost of £3.97 per day, significantly higher than the cost ZD and most othet typical antipsychotics.

Amisulpride (atypical antipsychotic)
Aripiprazole was replaced by amisulpride, a dopamine antagonist which has a high affinity and selectivity for the D2 and D3 receptors. It uses the same principle, reduction of dopaminergic activity to reduce positive symptoms, but has a higher selectivity for the mesolimbic system due to its selectivity for D3 receptors which are more prevalent in this region. This widens the therapeutic index so that the risk of EPS is reduced. Approximately one week after beginning amisulpride, EM’s delusions began to subside and he became calmer and more compliant. The only side effect he has experienced so far is the sedation due to histamine antagonism.

The net price of a 200mg 60 tablet pack of amisulprides is £55.87, so 400mg a day costs £1.86, so a good intermediate between ZD and aripiprazole in terms of its cost effectiveness.

C.ii. Psychosocial/ service level interventions
Psychosocial interventions for schizophrenia have developed over the past three decades due to the evidence of psychosocial processes involved in psychosis (see section D).

Music therapy
EM took part in active music therapy and felt it helped improve his mood as he enjoyed banging the drums to relieve his anger. It aims to produce an atmosphere where the patient can express and process strong emotions and help build a relationship with the therapist that would be limited by regular means of self expression. It has been shown to improve global state, metal state and social functioning, and is especially beneficial in reducing negative symptoms, such as the affective flattening EM displayed. EM has had no other psychological therapies as his psychosis responds well to medication. The coat of arts therapies ic approximately £100-£135 per person.

The crisis resolution and home treatment team (CRHTT)
The CRHTT was developed in order to treat acute episodes of mental health illnesses within the community, during and outside of office hours. The reson the do this in the community?They were visiting EM to monitor his mental health during the change in medication and quickly sent a member of the team to assess EM when alerted to the change in his mental health. However they felt EM could not be managed in the community and had to be admitted for proper supervision. The CRHTT are also likely to play a role in his aftercare by monitoring him for some weeks after he is sent home, to check his mental health is continuing to improve with amisulpride and to monitor side effects of the drug. This is a service level intervention which has clear benefit to his psychosocial wellbeing since being admitted to a mental health unit can be a stressful experience.

D. Psychosocial issues and public health
This section will address the different psychosocial aspects which should be taken into consideration in EM’s case and the cost effectiveness of treating schizophrenia.

D.i. Cost effectiveness
Schizophrenia accounts for 3% of the total expenditure by the NHS, so it is important to consider the cost effectiveness of interventions. Amisulpride and aripiprazole are more expensive than the typical antipsychotic, ZD. For Amisulpride this is justified ats it has been found to be more efficacious and provide a better quality of life then typical antipsychotics, however aripiprazole has neither of these benefits, yet is more expensive making its cost effectiveness questionable. 52% of the NHS expenditure on schizophrenia is accounted for by hospitalisation, CRHTT reduces these costs in the short term so is considered cost effective by NICE. Art therapies are considered cost effective as the benefit in quality of life continue for up to six months after treatment and is the only intervention found to have a large effect on negative symptoms.

D.ii. Psychosocial issues
The psychosocial aspects of schizophrenia closely interact with the biological factors as displayed in the causal model.

Precipitating factors
EM believes his first psychotic episode was brought on by stress due to problems at work and at home. Stressful life events are a precipitating factor in 60% of patients, and are thought to cause psychosis through stress intolerance and the neurobiological effects of the stress cascade. Stress induces the release of cortisol via the hypothalamic-pituitary-adrenal (HPA) axis, and chronic stress resulting in persistently high levels of glucocorticoids that can cause changes in the brain which contribute to the psychopathology in schizophrenia (fig 3). There is also a possibility that stress can trigger psychosis by augmenting dopamine activity, the significance of which is highlighted below in the dopamine hypothesis.

EM is a first generation immigrant to the UK, a factor associated with a 3% lifetime risk of developing schizophrenia and has been linked to persecutory delusions.* This could be linked to factors which many immigrants may experience, such as low socio-economic status, poor education, victimisation and feeling powerless, which can lead to feelings of control and mistrust that may contribute to paranoid thinking.

Perpetuating factors
Stress was an important precipitating factor for EM, it has also played a role in some of his relapses. Stress is a good example of the interactions in the biopsychoscoial model, as sociological aspects cause psychological stress which manifests biologically through the HPA axis causing the release of cortisol. The stress vulnerability model explains the relationship between the two (fig).

and even recollection of these events can lead to relapse. EM relapsed on the anniversary of his father’s death, and the anniversary of his mother’s death was a fortnight later, so it could be the recollection of these events played a part in triggering his relapse.

EM’s non compliance with his medication has occurred for 2 reasons, a lack of insight and the intolerability of the side effects, although his most recent relapse was due to a change in medication this was also due to the side effects. Both of these factors have a psychosocial basis. Quality of life, impact of stress on psychology.

The community mental health team (CMHT)
The CMHT is a multidisciplinary team that are important in recognising the need for psychosocial interventions. While giving his depot injections, the CMHN would assess his mental health and general wellbeing. The CMHN also helped EM begin private Spanish tuition, which helped him fill his time and improve his mood. The CMHN can refer to other members of the team, such as social workers, occupational therapists and psychologists, to provide psychosocial aid when necessary, helping EM to manage his life in order to stabilise his psychological wellbeing.

For EM, every day has become a struggle against schizophrenia. As research into the aetiology, pathophysiology and treatment advances, it is hoped that in future his burden may be lightened.