Psychotic Disorders - Lieberman & First (2018) - Article

A psychotic disorder refers to a condition where psychotic symptoms meet the criteria for a disease. Psychoses can be characterized in three groups:

1. Idiopathic psychoses. Causes a rapid decline in functional capacity. It is an abrupt onset of symptoms.
2. Psychoses due to medical condition. For example, neurodegenerative disorders.
3. Toxic psychoses. Due to substance abuse.

These three classifications are not fixed, they reflect the current lack of knowledge on psychotic disorders and their causes.

What are the differences between type I and type II psychosis?

The most frequent period in life where psychotic symptoms appear is in the third phase of life. However, this varies depending on the underlying disorder. Delusions often appear in middle ages, psychosis caused by drug abuse or medicine can occur at any age. Type II psychoses include toxic and psychoses due to a medical condition.  Idiopathic disorders, and more specifically schizophrenia or depression have an unpredictable course of their illness. The number of psychosis differs from one patient to another. In general, psychotic persons are at high risk for suicide attempts, substance abuse, homelessness and violence.

What are causes of the development of psychoses?

Many disorders are caused by an alteration of neurotransmission in the pathways of glutamate and dopamine in the brain. These are situated in the hippocampus, midbrain, corpus striatum and prefrontal cortex. Excess synaptic levels of glutamate and dopamine cause increased stimulation which can result in psychotic symptoms. In molecules, the disruption is a deficiency of the y-aminobutyric acid (GABA) inhibition neurons and N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs). The neural balance of dopamine cannot be regulated and results in an increased level of glutamate.  

Research is done by examining the neural consequences of taking cannabinoids (especially cannabinoid-I receptors). They guide the traffic of glutamate and dopamine. Synthetic drugs work in a similar manner releasing dopamine and serotonin in the brain. These drugs can induce psychotic symptoms. Psychedelic drugs stimulate the 5-HT_2A which implicates that 5-HT_2A  and serotonin are in the pathophysiology of psychosis. However, psychological drugs induce qualitatively different psychosis than idiopathic disorders.

What are genetic factors in psychosis?

Idiopathic psychotic disorders are heritable. The specific genes responsible for this heritability is not clear. Two hypotheses are defined:

1. The common disease-common allele hypothesis where prevalent genes with low penetrance act through other genes to confer a risk of developing a psychotic disease. However common genetic variants with low penetrance are not biologically plausible. However, there is some evidence the major histocompatibility complex (MHC) can de-regulate the development of neural connections in presynaptic terminals. This way is can influence the form and function of neural circuits.
2. The common disease-rare allele hypothesis where rare mutations of (novo mutations) that occur in a small proportion but are highly penetrant cause the psychotic disease. Rare genetic variants with high penetrance are mostly associated with psychotic disorder. The 22q11.2 deletion syndrome (also known as DiGeorge syndrome) is associated with schizophrenia. Similar copy-variations are associated with psychotic disorders.

What are neurodevelopmental factors in psychosis?

Maternal infections of nutritional deficiencies in the prenatal period are associated with the development of psychoses. Autoimmune and inflammatory disease can stimulate or block the glutamate system because of antibody regulation. Systemic autoimmune disorders are related to autoimmune diseases with nerve system manifestations such as SLE. Paraneoplastic and nonparaneoplastic autoimmune syndromes cause antibodies to be directed against the glutamate NR1 unit of NMDAR.

How is the diagnosis of a psychosic disorder?

Psychotic disorders are diagnosed clinically, based on observed behaviour, subjective reports and the history of the patient. Also, diagnostic tests such as EEG, genotype and toxicology are examined. Some of these tests reveal differences between psychotic and non-psychotic patients none have proved to be reliable in diagnosing individual cases of psychosis. There are three important diagnostic tests to expose the biological basis of psychosis.

1. Neuroimaging (MRI or PET) is used to reveal abnormalities in the brain that cause schizoaffective disorder, schizophrenia or bipolar disorder. The temporal, frontal and parietal lobes are reduced in size as well as cortical thickness. Magnetic resonance spectroscopy shows increased glutamate levels in the prefrontal and temporal lobes.
2. Neurophysiological tests (EEG) are conducted when a neurodegenerative or causative medical condition is assumed. Event-related potentials are abnormal in patients is psychotic disorders.
3. Serologic test for syphilis is recommended in psychosis. The immunologic conditions should be considered when the onset of psychotic symptoms is very sudden.

How is psychosis treated?

Psychoses can be treated with medicine. These work on dopamine and D2 receptors. Their effectiveness depends on the safety profile of the patient which varies with the underlying cause and previous pharmacology. Most patients are treated with short-acting medicine that requires daily administration. Long-acting medicine (haloperidol, olanzapine) are available and can facilitate adherence to the treatment. Effects of antipsychotics are moderate, and efficacy limited. Other medicines work on the 5-HT_2A receptor. These are useful for psychotic symptoms that are caused by dopamine, such as with Parkinson. However, they are less effective in treatment of schizophrenia and mood disorders. A careful review of the patients’ condition and medical history is needed before antipsychotic drugs are considered.

Another way of treatment is brain-stimulation such as ECT, TMS, DBS or tDCS. For example, ECT is affective for catatonia but also for mood disorders (depression) and schizoaffective disorders unresponsive to anti-psychotics. A promising effect is that auditory or verbal hallucinations can be controlled. When tDCS is applied over the auditory cortex this can result in less hallucinations and decrease of negative symptoms such as apathy and social withdrawal. Then, DBS is the most invasive and used when all other treatments fail.

Psychosocial approaches, such as behavioural rehabilitation consists of social skills training in which patients receive instructions about appropriate ways of behaviour and communication. Another psychosocial treatment is family psychology education. Cognitive behavioural therapy (CBT) may also be useful because it includes cognitive restructuring. CBT in patients with schizophrenia can reduce distress caused by hallucinations of delusional beliefs.

BulletPoints

• A psychotic disorder refers to a condition where psychotic symptoms meet the criteria for a disease. Psychoses can be characterized in three groups:

1. Idiopathic psychoses. Causes a rapid decline in functional capacity. It is an abrupt onset of symptoms.
2. Psychoses due to medical condition. For example, neurodegenerative disorders.
3. Toxic psychoses. Due to substance abuse.

• Psychotic disorders are diagnosed clinically, based on observed behaviour, subjective reports and the history of the patient. Also, diagnostic tests such as EEG, genotype and toxicology are examined. Some of these tests reveal differences between psychotic and non-psychotic patients none have proved to be reliable in diagnosing individual cases of psychosis.

ExamTickets

• Make sure you can explain the difference between type I and type II psychoses.
• What are heritable (genetic factors) of psychoses and what two hypotheses exist about the genetics?
• There are three ways in which psychoses are treated currently. One of them is psychosocial (social skills training). You should be able to name and explain the other two and list some of the sub-categories of these approaches.