Psychosis

1. Definitions
2. Organic Causes of Psychosis
3. Schizophrenia
   
   • Risk Factors
   • Symptoms
   • Pathophysiology of Schizophrenia
   • Drug Treatment of Schizophrenia
4. Drug-Induced Psychosis
5. Affective Psychosis
6. Postpartum Psychosis
7. Quiz

• Psychosis can be broadly defined as a family of symptoms in which the patient’s experience is outside the normal experience of reality. This includes delusions and hallucinations. Patients may also lack insight, meaning the patient will not entertain the idea that these beliefs are false.
• Psychosis can have organic (physical) causes: delirium (acute confusion), post-ictal (after a seizure), encephalitis (brain inflammation), or drug intoxication (being under the acute effects of a drug).
• Psychosis can also have a functional cause i.e. there is no underlying physical cause.
• An example of a psychotic disorder is schizophrenia, a condition in which patients interpret reality abnormally. Some symptoms of schizophrenia are known as Schneider’s First Rank Symptoms. These are delusional perception (a normal perception that suddenly takes on a false, personal meaning), third-person auditory hallucinations (voices talking about the patient), somatic hallucinations (bodily sensations felt to be imposed by an outside force), thought interference (thoughts felt to be inserted, taken out or broadcast) and passivity phenomena (actions or feelings felt to be controlled by an outside force). Symptoms of schizophrenia are also grouped as positive (such as hallucinations and delusions) and negative (such as withdrawal from others and flat emotion).
• There are multiple hypotheses for the pathophysiology of schizophrenia including dopamine and autoimmune.
• Drug treatment of schizophrenia uses antipsychotics (medicines that reduce psychotic symptoms), usually alongside psychological treatment. Both first-generation and second-generation antipsychotics block dopamine D2 receptors. One hypothesis is that second-generation drugs bind less tightly (a lower affinity) and so cause fewer movement side effects.
• Drug-induced psychosis involves hallucinations or delusions caused by substance exposure or withdrawal. The symptoms go beyond what intoxication alone would explain and are not part of delirium. They usually go away (remit) within a month of stopping the substance.
• Affective psychosis describes psychotic symptoms occurring in a mood disorder. The psychotic symptoms may match the patient’s mood (mood-congruent) or not (mood-incongruent).
• Postpartum psychosis usually begins suddenly in the first two weeks after birth, although later presentations occur. It is a medical emergency.

Definitions

Psychosis is a collection of symptoms characterised by the patient having experiences outside the normal experience of reality. This includes delusions and hallucinations. Psychosis is not a diagnosis in itself.

A hallucination is a sensory perception without an external stimulus. It can involve any sense (sight, hearing, smell, taste or touch). Hallucinations can be normal, for example, hypnagogic hallucinations (those that occur just before falling asleep).

Delusions are fixed, firmly held beliefs that are usually false. They are outside the patient’s cultural norms and unshakable (i.e. they cannot be reasoned away, even with evidence). It is important that these beliefs are outside of cultural norms - some might classify religious beliefs as delusional, but as these are within the cultural norms of the patient, they are normally not considered as such.

Insight is the degree to which a patient is aware of their condition and its relation to their symptoms. In psychotic disorders, a lack of insight is common.

Organic Causes of Psychosis

Psychosis can occur due to organic, physical causes. It is therefore important when a patient presents to healthcare services to investigate and treat these physical causes first.

• Delirium - an acute confusional state which may include psychotic symptoms. Can be caused by many things, including infection, constipation, hypoxia (low oxygen levels), and electrolyte disturbances (abnormal blood levels of salts such as sodium).
• Delirium Tremens - delirium (acute confusion) caused by withdrawal of alcohol in a person who is dependent on it. It can include tremor, hallucinations and seizures.
• Post-ictal Psychosis - occurs following a seizure.
• Encephalitis - inflammation of the brain tissue. It can be caused by an infection or by the immune system mistakenly attacking the brain (see anti-NMDA encephalitis below).
• Drug Intoxication - being under the acute effects of a drug or alcohol. Multiple prescription and illicit drugs can induce psychosis. Psychosis that goes beyond the usual effects of intoxication is covered under drug-induced psychosis below.

Schizophrenia

Schizophrenia is a condition in which patients interpret reality abnormally. It may result in hallucinations, delusions, disordered thinking and abnormal behaviours that impair daily functioning.

Risk Factors

Like all psychiatric disorders, risk factors for schizophrenia can be categorised into predisposing, precipitating and perpetuating factors.

Predisposing

Predisposing factors are factors that the patient cannot change and that accumulate to increase the likelihood of schizophrenia. They include:

• Genetics - family history
• Childhood abuse
• History of substance misuse
• Age: onset peaks around 20 to 25 years in males and 25 to 30 years in females

Precipitating

Precipitating factors are factors that exist in the patient’s life that, combined with predisposing factors, encourage the presentation of schizophrenia at that point. Examples include:

• Use of cannabis or psychostimulants (stimulant drugs such as cocaine or amphetamines)
• Adverse life events such as the death of a parent

Perpetuating

Perpetuating factors are factors that encourage the persistence of the symptoms of schizophrenia once it is already established. They are often seen as barriers to successful treatment. Examples include:

• Continued substance misuse
• Poor social support
• Poor adherence to medication

Symptoms

Symptoms of schizophrenia are usually classified as positive or negative. Positive symptoms are any change in behaviour or thoughts, such as hallucinations or delusions. Negative symptoms are where people withdraw from the world around them, take no interest in everyday social interactions and often appear emotionless and flat.

Dr Kurt Schneider proposed in 1939 that a set of symptoms were of first-rank importance in diagnosing schizophrenia. They are known as Schneider’s First Rank Symptoms. They can be seen in schizophrenia but are not specific to it and may occur in other psychotic illnesses. DSM-5 (the American Psychiatric Association’s diagnostic manual) no longer gives them special status, and ICD-11 (the World Health Organization’s classification of diseases) gives them less emphasis.

• Delusional Perception - a normal perception that suddenly takes on a false, personal meaning, for example seeing a red car and suddenly knowing that it means they are being watched
• Third-Person Auditory Hallucinations - hallucinations that are heard in the third person, often in the form of running commentary, for example “he’s brushing his teeth, now he is turning on the tap”
• Physical (Somatic) Hallucinations - bodily sensations that the patient feels are being imposed by an outside force, for example feeling that a machine is moving or heating their organs. This is also called somatic passivity
• Thought Interference
  
  • Thought Broadcast - thoughts are being made known to others, e.g. being played on the radio
  • Thought Withdrawal - thoughts are being taken out of the brain
  • Thought Insertion - thoughts that are not the patient’s own are being implanted into their mind by an outside force
• Passivity Phenomenon - actions or feelings are being caused by an external force, e.g. “the police have been moving my leg”

Pathophysiology of Schizophrenia

The exact pathophysiology of schizophrenia (how the illness develops and which changes in the body underlie it) is not known. Several abnormalities are thought to contribute.

Dopamine Hypothesis

The mesolimbic pathway uses dopaminergic neurones (neurones that release dopamine) to connect the midbrain (the top part of the brainstem) to the limbic system (a network of brain areas involved in emotion and memory). It manages reward and pleasure. The mesolimbic pathway is thought to be overactive in schizophrenia.

The mesocortical pathway uses dopaminergic neurones (neurones that release dopamine) to connect the midbrain (the top part of the brainstem) to the frontal cortex and the cingulate gyrus (a fold of cortex involved in emotion and attention). It manages cognition (thinking and reasoning) and emotional response. The mesocortical pathway is thought to be underactive in schizophrenia.

Autoimmune Hypothesis

A condition called Anti-NMDA encephalitis (anti-N-methyl-D-aspartate receptor encephalitis) can also present similarly to schizophrenia. In this condition the body produces antibodies against its own NMDA receptors. These receptors normally respond to glutamate, an excitatory neurotransmitter (a chemical messenger that makes neurones more likely to fire). The antibodies cause the receptors to be taken into the neurone (internalised), so there are fewer receptors on the cell surface and less NMDA receptor signalling. This is thought to cause symptoms like those of schizophrenia. The brain also becomes inflamed (encephalitis).

Because it can look like schizophrenia, Anti-NMDA encephalitis has sometimes been mistaken for it. It is a separate condition that can be treated with immunotherapy (treatment that suppresses or adjusts the immune system, such as steroids). Most patients respond to immunotherapy. In a large observational cohort study (a study that follows a group of patients over time), 81% of the patients followed up at 24 months (203 of 252) had a good outcome. NICE advises that the assessment of a person with psychosis includes a physical examination to identify physical illness (including organic brain disorders).

Drug Treatment of Schizophrenia

Antipsychotics (medicines that reduce psychotic symptoms) are the main drug treatment for schizophrenia. For a first episode of psychosis, NICE recommends oral antipsychotic medication together with psychological interventions (family intervention and individual cognitive behavioural therapy). The patient and the healthcare professional choose the drug together. Before treatment starts, baseline checks include weight, waist circumference, pulse, blood pressure, blood glucose or HbA1c (a measure of average blood glucose), blood lipids and prolactin (a hormone that some antipsychotics raise).

Typical (first-generation) antipsychotics were the first antipsychotics developed. They block dopamine D2 receptors in the dopaminergic pathways (the pathways that use dopamine) of the brain, which reduces psychotic symptoms. Dopamine is also needed in other pathways, so blocking it there can cause side effects. These side effects are especially noticeable when the nigrostriatal pathway (the dopamine pathway that helps control movement) is blocked. This causes symptoms of Parkinsonism - slowed movements, tremors and muscle rigidity. Other movement side effects include acute dystonia (painful muscle spasm), akathisia (restlessness) and tardive dyskinesia (involuntary movements that can develop with long-term use).

Atypical (second-generation) antipsychotics also act on D2 receptors. One hypothesis is that they have a lower affinity (they bind less tightly) and come off the receptor faster (fast dissociation). This may make them less likely to cause movement side effects. They can cause other side effects, such as weight gain and diabetes. Individual antipsychotics differ substantially in their side effects, so the choice of drug is made for each patient.

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