**6. Application of our model to explain the pathogenesis of schizophrenic psychosis**

In our opinion, a weak point of Kapur's model is the starting point that the aberrant salience attribution is due to a dysregulated, hyperdopaminergic state. This is not necessarily true. Actually, the hyperdopaminergic state could result from dysregulation on every level within the corticoid amygdala to midbrain monoaminergic area chain, including input from neocortical areas to the corticoid amygdala and the influence of the habenula to relevant midbrain structures. In most psychotic disorders, the hyperdopaminergic state may not induce aberrant salience, but may result from it. This does not exclude that increased sensitivity to the effects of dopaminergic transmission may increase the vulnerability to become psychotic.

So, we propose that the primary dysregulation which causes psychotic symptoms in 'schizophrenia' is localised within the interaction between the corticoid amygdala, in interaction with neocortical fields, with midbrain monoaminergic centres. The ventromedial prefrontal cortex may be the principle pathway for the corticoid amygdala to interact with these other cortical areas. Via connections through the habenula, the amygdaloid complex regulates the activity of the midbrain monoaminergic centres which in turn regulate motivation to exhibit reward-seeking or misery-fleeing behaviour. Increased dopaminergic input to the basal ganglia may induce behavioural hyperactivity and to the parahippocampal region may lead to hallucinations [94]. The amygdaloid complex is also innervated with dopaminergic fibres. Dopamine may lead to increased sensitivity of the amygdala to induce an emotional response. Psychotic disorders may be due to increased dopaminergic activity within the amygdaloid complex, aberrant salience attribution due to genetic or learned (conditioned) neuronal faults or aberrant inhibition by the dorsomedial prefrontal cortex due to neurodegenerative network failure. However, the hyperdopaminergic state is probably not the essential factor causing schizophrenic psychosis, and this may explain why antidopaminergic agents, as are all current antipsychotic drugs, are not always effective in treating schizophrenic psychosis.
