It came, of course, from Shitij Kapur and his groundbreaking theory of psychosis published a long time ago, in 2003. This was followed by the formulation of the third dopamine theory of schizophrenia, which was done by Oliver D. Howes and Shitij Kapur in 2009. And in the same year, Jim van Os proposed renaming schizophrenia as the aforementioned 'salience syndrome'.

So yes - the first dopamine theory of schizophrenia was the holistic theory, saying that schizophrenia is caused by dopaminergic dysfunction. It was finally formulated in the 1970s and was a receptor theory. According to it, blockade of dopamine receptors was supposed to cure schizophrenia. It turned out that the issue was a bit more complicated and in 1991 Davis and colleagues published the 2nd dopamine theory of schizophrenia. In this new version, the matter was more complex because the authors added to the hypothesis differences relating to the action of particular areas of the brain. In the previous version, the 'whole brain' had too much dopamine. And in the new version? ... it depends. In the frontal lobes it turned out to even have too little of it (hypodopaminergic), but in the subcortical nuclei too much (hyperdopaminergic). This formulation made it possible to differentiate between the negative and positive symptoms of schizophrenia and to relate them to particular areas of the brain (frontal hypodopaminergia associated with negative symptoms, hyperdopaminergia in the striatal nuclei - associated with positive symptoms). Beautiful! But what's next?

Next came Kapur, who did an amazing thing - he linked changes at the level of biology to what a person in psychosis subjectively feels. The third dopamine hypothesis is actually a theory of psychosis in schizophrenia. No longer of all schizophrenia, no longer of all symptom groups, but as Howes and Kapur write "the dopamine hypothesis of psychosis in schizophrenia". He says that disruption of dopamine transmission is the ultimate common outcome, to which many different pathways can lead. It could be: complications of pregnancy and confinement, it could be 'problematic' upbringing, it could be drug use, social isolation, low social status, psychological trauma, migration, etc. But at the end of these various pathways comes impaired dopamine function. Thus, the problem is not with D2 receptors, but with presynaptic dopamine function, that which is upstream of the synapse, not downstream of it. Thirdly, this impaired dopamine function is related to psychosis rather than to schizophrenia as such. And fourthly, dysfunction of the dopaminergic system leads to increased capture (relating to oneself) of stimuli and stimulation from the environment, which can lead to the development of psychosis. The fragment of the dopaminergic system we are talking about here acts as a detector of new, relevant meanings in the environment. If its function is out of control - everything the person perceives is new, meaningful and pertinent to him or her - isn't this xobia commonly known from clinical practice? If this xobia progresses - delusions are formed as psychological explanations for what the psychotic person subjectively perceives. What of this (among other things)? Howes and Kapur write straightforwardly - the antipsychotics available so far do not treat the root cause of the disorder, they act on its sequelae (from the side of the sequelae of the dysfunction they act as if retroactively).