Schizophrenia

Schizophrenia is a psychotic disorder marked by positive symptoms like hallucinations and delusions, as well as negative symptoms such as reduced speech, flat affect, and anhedonia.

Pathophysiology

1. Comes from the Greek words schizo which means split and phren which means mind.
2. The dopamine hypothesis is a key proposition to the underlying pathogenesis of schizophrenia. It essentially states that an abnormality in dopamine transmission results in the symptoms seen in schizophrenia.
3. There are two key neural pathways, the mesolimbic and mesocortical pathway that are thought to be involved in schizophrenia. It is thought a hyperactivity of dopamine in the mesolimbic pathway results in positive symptoms seen in schizophrenia, whilst the underactivity of dopamine in the mesocortical pathway results in the negative symptoms of schizophrenia.  
4. Antipsychotics mainly work by blocking D2 receptors (one of the 5 types of dopamine receptor), which is seen to help reduce the symptoms of schizophrenia.
5. Other neurotransmitters have also been implicated including glutamate, GABA, and serotonin.
6. Structural brain changes have also been seen in patients with schizophrenia such as:
   • Reduced gray matter: Potentially due to neuronal loss
   • Reduced white matter: Potentially due to alterations in myelination
   • Increased CSF: Possibly related to brain atrophy

Risk Factors

• Low birth weight
• Maternal stress/infection
• Winter births
• Birthing trauma
• Childhood trauma
• Afro-Caribbean heritage
• Cannabis use
• Family history
• Urban living

Clinical Features

These are split into the positive and negative symptoms.

Positive

• Hallucinations: Often auditory and can often be a running commentary, conversing voices, or discussion of the patient in the third person
• Delusions: Firm and fixed beliefs that are not based on specific grounds
  • Passivity: Patient believes they are being controlled by something else
  • Persecutory: False and irrational belief that someone is actively trying to harm or persecute the individual
• Thought abnormalities:
  • Thought insertion/withdrawal: Delusion where the patient believes thoughts are being put into, or removed, from their brain
  • Thought broadcasting: The feeling that their thoughts can be heard by others
  • Thought echo: Experience of hearing own thoughts spoken back to patient a few seconds after having had a thought
  • Thought blocking: Suddenly losing place in speech – patients will abruptly stop talking
• Neologisms: Formation of new words
• Loosening of associations: Speech will not be sequential or related in nature

Negative

• Blunted affect
• Apathy
• Anhedonia
• Alogia (poverty of speech): Brief responses to questions

Schneider’s First Rank Symptoms

These are symptoms noted by the psychiatrist Kurt Schneider as possibly diagnostic of schizophrenia. They do occur in other conditions, but specifically these symptoms should raise suspicion of schizophrenia:

• Auditory and/or somatic hallucinations
• Thought possession abnormalities: Withdrawal, insertion, broadcasting, interruption
• Delusional perception: This is when inappropriate meaning is given to a normal and present perception. For example, seeing a flower (which is real) and taking this to mean aliens are about to arrive.
• Passivity: Feeling as though one is being controlled

Differential Diagnosis

• Illicit substances e.g. amphetamine psychosis
• Bipolar affective disorder/mania
• Schizotypal disorder: Flat emotions, lacking relationships outside of immediate family, social anxiety, unusual/eccentric thinking. There can be transient psychosis in schizotypal disorder, but this is usually brief and not as severe as what is seen in schizophrenia. Patients will also usually have insight.
• Organic brain disease: Wilson’s disease, encephalitis etc

Investigations

Bedside

• ECG: To exclude abnormalities particularly prior to treatment
• Urine toxicology screen

Bloods

• FBC, U&E, LFT: Baseline, particularly prior to starting antipsychotics
• Thyroid function test: Abnormal thyroid function can cause psychotic symptoms
• Dexamethasone suppression test: Cushing’s may present with psychosis although rarely
• Blood glucose and lipid screen: Pre-treatment due to the risk of a metabolic syndrome with atypical antipsychotics

Imaging

• CT/MRI Head: To look for structural abnormalities or other organic disease such as encephalitis that may be causing psychosis

Management

Psychosocial Interventions

• CBT
• Art therapies
• Family intervention

Antipsychotic Drugs

Antipsychotics are the mainstay of treatment in schizophrenia. They can be split into two major classes – typical, and atypical drugs. They can be given orally, or as long-acting depot injections, the latter of which can help prevent non-compliance and reduce hospitalisations.

Atypical

Associated with weight gain and metabolic syndrome (dyslipidaemia, blood sugar abnormalities)

• Olanzapine
• Risperidone
• Aripiprazole
• Quetiapine
• Clozapine: Generally used when treatment failure has occurred with 2 other antipsychotics. Need to monitor extremely carefully due to the risk of agranulocytosis – should not be given to patients who cannot regularly attend follow-up for repeat bloods.

Typical

These are more likely to cause extra-pyramidal side effects.

• Haloperidol: Can cause QT prolongation and arryhtmias
• Chlorpromazine
• Prochlorperazine
• Levomepromazine

Antipsychotic Side Effects

• Extra-pyramidal side effects: Arise as a consequence of blocking of D2 receptors. They are more common in typical drugs, and atypical drugs carry a lower risk of these.
  • Tardive dyskinesia: Involuntary/repetitive movements of the body such as sticking out the tongue or grimacing
  • Akathisia: Feeling restless resulting in repetitive movements such as shifting, swinging of the legs, pacing etc
  • Acute dystonia: Often painful, results in constant muscle contraction
  • Parkinsonism: Shuffling gait, bradykinesia, tremor
• Amenorrhoea/galactorrhoea/gynaecomastia: Due to inhibition of dopamine, resulting in an increase of prolactin (in normal physiology, secretion of dopamine results in inhibition of prolactin secretion)
• Sedation: Due to the antihistaminergic effects of these drugs
• Anticholinergic effects: Dry mouth, constipation, urinary retention
• Postural hypotension: Secondary to alpha-adrenal receptors

Neuroleptic Malignant Syndrome

A rare but life-threatening condition mostly seen with both typical and atypical antipsychotics, although the risk is higher with typical drugs. It is thought to occur due to the sudden blockage of dopamine activity in the brain.

• Fever
• Confusion
• Muscle rigidity
• Hyperthermia
• Tachycardia
• Sweating
• Elevated CK
• Impaired renal function

Management involves stopping the drug and supportive treatment such as cooling and hydration. In some cases, dopamine agonists are considered such as bromocriptine.

References

https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1188603/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032934/

https://www.nice.org.uk/guidance/cg178/chapter/Recommendations#first-episode-psychosis-2

https://pubmed.ncbi.nlm.nih.gov/1359485/#:~:text=Extrapyramidal%20symptoms%20are%20caused%20by,pathologies%20of%20the%20extrapyramidal%20system

https://www.ncbi.nlm.nih.gov/books/NBK519503/

https://www.ncbi.nlm.nih.gov/books/NBK482282/

https://www.bap.org.uk/pdfs/BAP_Guidelines-Schizophrenia2.pdf