Schizophrenia is a serious mental illness characterized by loss of contact with reality, hallucinations, delusions, bizarre thoughts and impaired functioning. The diagnosis of ‘schizophrenia’ is made on the basis of symptoms that occur in varying combinations. Furthermore, the prognosis varies greatly: schizophrenia goes away in some people, while others do not recover or deteriorate further.
Symptoms
According to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), psychotic disorders are divided into schizophrenia, schizophreniform and schizoaffective disorders, short-term psychotic disorder, delusional disorder and psychotic disorders caused by medication, toxic substances or substance abuse, delirium, alcohol withdrawal symptoms and delirium in dementia.
The DSM-IV diagnostic classification system summarizes the symptoms of schizophrenia into 5 categories :
- Delusions
- Hallucinations
- Negative symptoms
- Incoherent behavior
- Severely chaotic and catatonic behavior
Positive symptoms (excess normal functions, type I)
The positive symptoms may be due to hyperactivity of the dopaminergic systems, especially in the limbic region of the brain. Positive symptoms are symptoms that are additional and are regulated via the limbic system. Someone with schizophrenia may imagine something that does not match reality.
- Delusions:
- Belief in a higher power
- Paranoia: Believing that you are being persecuted or the victim of a conspiracy. Believing that someone wants to kill or harm him
- Delusions of Relation: Believing that media reports have meaning specifically for him
- Delusions of identity, delusions of grandeur: believing that he is a special person, such as an emissary of God, or someone with extraordinary gifts.
- Hallucinations. Hallucination is a perception (hearing, seeing, smelling, etc.) that is not shared by others. ‘Hearing voices’ and ‘seeing things’ are the most common. The voice can provide constant commentary, advice or commands. The person can answer the voice, making it seem like they are talking to themselves.
- Formal thought disorders
Negative symptoms (decrease in normal functions, type II)
The negative symptoms may arise as a result of reduced prefrontal cortical activity.
Negative symptoms are all that go off; social decline. Referring to the absence or attenuation of something: decisiveness, emotion, speech, thoughts.
- Lack of energy and motivation. Someone with schizophrenia may have difficulty starting or finishing something. He can no longer study or work, maintain social contacts, relax or take good care of himself.
- Flattening of the emotional life. (affective flattening). A person with schizophrenia may give the impression or even have the impression that his feelings and emotions have disappeared or been blunted.
- Initiative loss
- Apathy
- Quantitative and qualitative speech poverty
origin, development and course.
Not much is yet clear about the origins and progression of schizophrenia. There is, however, a hypothesis, the dopamine hypothesis, which is mainly based on two observations.
- Amphetamine is capable of producing symptoms that are very similar to those of schizophrenia. Amphetamine increases the release of dopamine, leading the symptoms to be suspected to be a consequence of dopaminergic hyperactivity
- All antipsychotics appear to be antagonists of dopamine D2 receptors. This indicates that reduction in dopaminergic neurotransmission may counteract certain symptoms of schizophrenia.
Weinberger’s hypothesis
The assumption is that in schizophrenia patients there is increased activity in the mesolimbic dopamine system and reduced activity in the mesocortical dopamine system. Normally the mesocortical system would inhibit the mesolimbic system through a feedback mechanism. In schizophrenia, there is a primary defect in the mesocortical dopamine system (reduction in activity), leading to no inhibition of the mesolimbic system and its hyperactivity. However, it has proven impossible
to detect increased dopaminergic neurotransmission in schizophrenia patients. Furthermore, antipsychotics appear to have no therapeutic effect at all in some patients, while the dopamine receptors are almost completely blocked and therefore no more dopaminergic neurotransmission takes place.
Because all dopamindergic receptors are then occupied, there are also some other things that can play a role. It is therefore important to influence other neurotransmitters. These are:
- Serotonin
- Glutamate (There would be a shortage of glutamate)
- GABA
Abnormalities in the brain area in schizophrenia
In particular, the prefrontal cortex and the temporal cortex (particularly the hypocampus) show abnormalities in many schizophrenia patients, possibly due to problems with neuronal migration at a late stage of cortical development. It has also been found that schizophrenic patients (particularly type II patients) have reduced blood flow to the prefrontal cortex. While type I patients often suffer from increased blood flow to the temporal cortex. Dilation of the lateral ventricles has also been observed in a large number of schizophrenic patients. Smaller size or less gray matter has also been found in brain areas such as the temporal and frontal lobe.
Degeneration of gliosis and neurons has been noted in schizophrenia, but these changes are not specific to these disorders. These changes may occur as a result of viral infection with the cytomegalovirus, but there is little evidence for this.
Causes
Various causes play a role:
- psychological factors (personality, stress)
- biological factors (brain development, brain processes)
- environmental factors
Heredity
The development of schizophrenia is partly genetically determined, but this genetic component is not necessary or sufficient for the development of the disease.
It is not about a single gene, but about interaction between several genes, and between these genes and environmental factors. Chromosomes 6 and 13 are mentioned as possible locations .
Chemical processes and neurotransmitters
The functioning of some neurotransmitters is said to be disrupted in schizophrenia. This mainly concerns dopamine and glutamate. Decreased glutamate activity in the cortical parts of the brain may play a role.
Glutamate is the most important neurotransmitter in the brain, affecting 50% of the synapses. The main glutamatergic system runs from the cortex to the striatum. Four glutamate receptors can be distinguished, the most important are:
- AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole)
- NMDA (N-methyl-D-aspartate)
Therapy
There are 2 forms of treatment for people with schizophrenia, which are also used in combination:
- medicated
- psychological therapy
Schizophrenia is often treated with a combination of antipsychotics and psychosocial support and guidance of the patient and his social environment (including day structuring, occupational rehabilitation).
Antipsychotics
Antipsychotics are medicines that can reduce or eliminate psychotic symptoms. They have an effect mainly on the positive symptoms and possibly (directly or indirectly) on the negative symptoms. Within antipsychotics, a distinction is made between classic/typical and atypical antipsychotics.
Mechanism of action of antipsychotics
The hypothesis is that blockade of postsynaptic dopamine type 2 (D2) receptors in the mesocortical and limbic brain region reduces or eliminates psychotic symptoms.
However, in patients who do not respond to (classic) antipsychotics or in whom too little reduction in psychotic symptoms is achieved, a complete D2 receptor blockade is also found. Brain research and the advent of new antipsychotic compounds have made it clear that dopamine (D2) blockade alone is not always sufficient for a satisfactory antipsychotic effect, and certainly not in schizophrenia. Influencing serotonin, glutamate and γ-aminobutyric acid (GABA) are also important.
Classic antipsychotics
The classic or typical antipsychotics include:
- butyrophenones (e.g. haloperidol). The strong affinity for the postsynaptic D2 receptor indicates that extrapyramidal disorders and (psycho)sedation are in the foreground.
- diphenylbutylamines (e.g. pimozide)
- Phenothiazines (e.g. thioridazine, especially with an aliphatic side chain) and to a lesser extent thioxanthenes relatively often lead to immunological reactions such as photosensitivity, pigmentation, rash, cholestasis, hepatitis (independent of cholestasis) and blood dyscrasias. Phenothiazines can also cause eye abnormalities. Furthermore, phenothiazines and other antipsychotics prolong the QT(c) interval.
- thioxanthenes (e.g. zuclopenthixol)
- some compounds that do not fall under these groups in terms of chemical structure.
A number of these compounds have a pronounced antidopaminergic (D2) effect.
Classic antipsychotics affect the brain and especially, but not only, the neurotransmitter dopamine. This probably explains part of their effect and at least some side effects.
The traditional remedies mainly target the positive symptoms of schizophrenia. They have little influence on negative symptoms and cognitive deficits.
Atypical antipsychotics
In general, atypical antipsychotics are compounds with a tendency to have fewer extrapyramidal side effects (there is a wide difference in dosage at which an antipsychotic effect is produced and at which extrapyramidal side effects are produced) and/or an efficacy in treatment-resistant patients and/or an efficacy in negative symptoms.
The most important advantages in the literature compared to classical antipsychotics are that atypical antipsychotics cause fewer extrapyramidal side effects and that they appear to have a greater effectiveness on negative symptoms.
These are considered atypical antipsychotics.
- Clozapine. Has a (moderate) antidopaminergic effect and a relatively high affinity for histaminergic (H1), serotonergic (5-HT2), α-adrenergic and cholinergic receptors. The antipsychotic effect could be explained by the combined blockade of D2 and 5-HT2 receptors.
- risperidone. Mainly has dopamine D2 and serotonin (5-HT2) blocking properties. The affinity for serotonin receptors is approximately 10 times higher than for dopamine receptors. During a period of use of 1 year, the risk of new exacerbation of psychosis (relapse) during treatment with risperidone (34%) is lower than with haloperidol (60%) and fewer patients prematurely discontinued treatment.
- Olanzapine. Has a blocking effect on a series of receptors, including serotonin 5-HT2 and dopamine D2 receptors. Extrapyramidal side effects occur less frequently than with haloperidol.
- Quetiapine. Has a broad receptor affinity with less affinity for dopamine D2 and serotonin 5-HT2 receptors than clozapine and olanzapine but more than haloperidol.
- Sulpiride, possibly in low doses. Has a slightly different receptor binding profile, in the sense that at low doses (up to approximately 600 mg per day) presynaptic D2 receptors are selectively antagonized. At higher doses (approx. 800 mg or more per day) there is also an influence on the postsynaptic D2 receptors, as with classic antipsychotics.