Schizophrenia

• Overview:

  • Long term mental health problem which affects thinking, perception and affect
  • Affects about 1 in 100 people
  • Affects men and women equally - onset tends to be slightly earlier in men
  • Usually diagnosed between the ages of 15 and 35
  • High incidence in urban areas and among migrants
• Aetiology:

  • Precise cause is unknown
  • Believed to be a consequence of a combination of psychological, environments, biological and genetic factors
  • Thought that some people may have a susceptibility to schizophrenia and that emotional life experiences can act as a trigger for developing the illness
• Pathophysiology - neurodevelopmental hypothesis:

  • People who have experienced hypoxic brain injury at birth or exposed to viral infections in utero are at a greater risk of developing schizophrenia
  • Those with temporal lobe epilepsy or who smoke cannabis while their brain is still developing are also at a higher risk
  • Suggests that brain development is implicated in the pathophysiology of schizophrenia
  • Imaging has shown changes in the brains of people with schizophrenia - enlarged ventricles, small amounts of grey matter loss and smaller, lighter brains
• Pathophysiology - neurotransmitter hypothesis:

  • Excess of dopamine and overactivity in the mesocorticolimbic system believed to cause the positive symptoms - hence why dopamine antagonists are used to treat
  • Less dopamine activity in the mesocortical tracts, causing the negative symptoms of schizophrenia - explains why dopamine antagonists are more successful at treating positive symptoms
  • Psychotic symptoms are seen with overtreatment of levodopa, amphetamines and cocaine - increase dopamine release
  • Other neurotransmitters - increase in serotonin activity, decrease in glutamate activity
• Risk factors:

  • Genetics - strong genetic link - 40% chance of developing schizophrenia if both parents affected. Also increased risk when father aged over 55
  • Pregnancy - malnutrition and viral infections increase risk. Pre-eclampsia and emergency caesarean
  • Drug abuse - using cannabis, particularly as a teenager increases risk. Many other drugs can cause psychotic symptoms
  • Social - more prevalent in urban areas and lower socioeconomic classes (but may be a consequence of living with schizophrenia). Stressful life experiences increase risk - seen in migrants and victims of sexual abuse
• In the United Kingdom, Afro-Caribbean men are more affected than other ethnicities.
• Symptom specifier:

  • Subtypes of schizophrenia from ICD-10 were removed and replaced with symptom specifier
  • Records information about the presence or absence of symptoms, their time course and response to treatment
  • 5 categories - positive, negative, depressive, manic, psychomotor, and cognitive deficits
  • Symptoms are assessed from 0 (absent) to 4 (severe)
• A prodrome phase often precedes the full symptoms of psychosis, patients may experience subtle symptoms:

  • Poor memory
  • Reduced concentration
  • Mood swings
  • Suspicion of others
  • Loss of appetite
  • Social withdrawal
• Psychosis is the central feature of schizophrenia. The key features of psychosis, called positive symptoms, are:

  • Delusions (beliefs that are strongly held and clearly untrue)
  • Hallucinations (perceiving things that are not real)
  • Thought disorder (disorganised thoughts causing abnormal speech and behaviour)
  • Lack of insight is also an important feature - not aware that delusions and hallucinations are not real
• Psychosis is the central feature of schizophrenia. The key features of psychosis, called positive symptoms, are:

  • Delusions (beliefs that are strongly held and clearly untrue)
  • Hallucinations (perceiving things that are not real)
  • Thought disorder (disorganised thoughts causing abnormal speech and behaviour)
  • Lack of insight is also an important feature - not aware that delusions and hallucinations are not real
• Positive symptoms:

  • Thought echo - hearing own thoughts out loud
  • Thought insertion or withdrawal
  • Thought broadcasting
  • Third person hallucinations - hear voices talking about them e.g. "he is an evil person"
  • Delusional perception - a true perception, to which a patient attributes a false meaning e.g. a traffic light turning red means aliens are coming
  • Passivity - thoughts or actions are controlled by external agent
  • Lack of insight
  • Formal thought disorder
• Schneider's first rank symptoms:

  • If present, strongly suggestive of schizophrenia:
  • Auditory hallucinations - thought echo, third person
  • Thought withdrawal, insertion and interruption
  • Thought broadcasting
  • Somatic hallucinations - perception of being touched
  • Delusional perception
  • Passivity - feelings or actions influenced by external agents
• Negative symptoms:

  • Blunted affect
  • Apathy/avolition
  • Social isolation
  • Poverty of speech (alogia)
  • Self-neglect
• Depressive symptoms:

  • Feelings of sadness
  • Feelings of emptiness
  • Anhedonia - inability to feel pleasure in activities
• Manic mood symptoms:

  • Euphoria
  • Expansiveness - extreme expression of emotion
  • Subjective experience of increased energy
• Psychomotor disturbance symptoms:

  • Catatonic restlessness - lack of movement and communication but also agitation, confusion and restlessness
  • Posturing
  • Stupor - only vigorous and repeated stimuli will arouse the person
  • Mutism
• Patterns of schizophrenia:

  • The active phase of symptoms may be:
  • Continuous
  • Episodic (relapsing and remitting)
  • A single episode only
• Categorisation of a presenting episode:

  • First episode
  • One of multiple episodes
  • Part of a continuous course
  • Unspecified
• Lab investigations to rule out other causes (if indicated)

  • Baseline bloods
  • Urine culture - infection causing delirium
  • Urine drug screen
  • HIV testing
  • Syphilis serology
  • Serum lipids - before starting antipsychotics
• A CT head can be done if an underlying organic cause of psychosis is suspected
• For a diagnosis, there must be some level of disturbance for at least 6 months. This 6 month period must include at least 1 month of active phase symptoms (or less if treatment successful) - persistent delusions, persistent hallucinations, disorganised thinking, and experiences of influence, passivity or control
• ICD-11 criteria:

  • At least 2 symptoms to be present for most of the time for at least 1 month - positive, negative, depressive, manic, psychomotor, or cognitive symptoms
  • AND of the two symptoms, one core symptom must be present:
  • Persistent delusions
  • Persistent hallucinations
  • Disorganised thinking
  • Experiences of influence, passivity or control
  • AND symptoms not a manifestation of another medical condition
• A specialist psychiatry service will manage patients with schizophrenia:

  • Early intervention in psychosis services are available for the first episodes of psychosis
  • Crisis resolution and home treatment teams provide urgent support for patients in a crisis
  • Acute hospital admission (under the Mental Health Act when required)
  • Community mental health team for ongoing monitoring and management
• Patients with schizophrenia will usually have a care programme approach (CPA).

  There are four stages to a CPA:

  • Assessing health and social needs
  • Creating a care plan
  • Appointing a key worker to be the first point of contact
  • Reviewing treatment
• Antipsychotics:

  • The medication to treat schizophrenia are D2 (dopamine) receptor antagonists
  • They can be divided into first generation (typical) and second generation (atypical) antipsychotics
• First generation antipsychotics:

  • Typical group are older and thought to primarily exert their effects by blocking D2 receptors
  • Examples - haloperidol, chlorpromazine, flupentixol decanoate (depot)
  • More likely to cause EPSEs
• Atypical (second generation) antipsychotics:

  • More selective in their dopamine blockade and also block serotonin 5-HT2 receptors
  • Act on negative symptoms as well as positive unlike typical
  • Less likely to cause EPSEe and usually cause milder hyperprolactinaemia
  • Olanzapine
  • Clozapine
  • Aripiprazole - partial dopamine agonist so less likely to cause EPSEs
  • Quetiapine
  • Risperidone
• Depot antipsychotics are given as an intramuscular injection every 2 weeks – 3 months. This can be helpful where adherence may be an issue. Examples include:

  • Aripiprazole
  • Flupentixol
  • Paliperidone
  • Risperidone
• Clozapine:

  • Used for treatment resistant schizophrenia - when 2 other antipsychotics have been ineffective
  • Only given orally
  • Very effective but significant side effects
  • Agranulocytosis - regular FBC needed
  • Myocarditis or cardiomyopathy
  • Constipation
  • Seizures
  • Excessive salivation
• Monitoring requirements before starting and during antipsychotic treatment include:

  • Weight and waist circumference
  • Blood pressure and pulse rate
  • Bloods, including HbA1c, lipid profile and prolactin
  • ECG
• Side effects of antipsychotic drugs:

  • Weight gain and increased risk of metabolic syndrome
  • Increased risk of T2DM
  • Prolonged QT interval
  • Hyperprolactinaemia - sexual dysfunction, increased risk of osteoporosis, amenorrhoea in women, galactorrhoea, gynaecomastia and hypogonadism in men
  • Anticholinergic - tachycardia, blurred vision, dry mouth, constipation, urinary retention
  • Neurological - seizures, neuroleptic malignant syndrome
  • Extrapyramidal side effects
• Other treatments:

  • Psychological - CBT, family therapy
  • ECT can be used for very severe or treatment resistant presentations
• Complications of schizophrenia:

  • Cardiovascular disease - increased risk of premature death, and patients are more likely to smoke
  • Suicide - lifetime risk 5%
  • Cancer - delayed diagnosis and late presentation
  • Substance abuse - present in up to 1/3
  • Social isolation
• Overall, the life expectancy of patients with schizophrenia is reduced by approximately 15 -25 years.
• There is no first-line antipsychotic drug suitable for all people with psychosis, and (except for clozapine) little meaningful difference in efficacy. Choice, therefore, depends on the person's personal choice, medication history, degree of sedation required, risk of particular adverse effects, and the degree of negative symptoms (second-generation more likely to help negative symptoms)