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Ever since the since the serendipitous discovery of the antipsychotic effect of chlorpromazine, the dopamine theory of schizophrenia has been the predominant one in both the understanding of its pathology and pharmacological management. Although this has had success in the management of positive symptoms of schizophrenia, this is not the case with negative symptoms of this disease. These are the ones which lead to the most long-term disability and consequent poor outcome. Pharmacological interventions for schizophrenia which concentrate on the dopaminergic pathways have had little success in alleviating negative symptoms of this disabling illness. Indeed, there has been a dearth of pharmacological initiatives addressing negative symptoms of schizophrenia. Drug development seems to have been led by identifying and targeting a single explanatory mechanism for the disease. While each proposed explanatory mechanism has clear merits, each also has limitations. The most probable neuropathological explanation of schizophrenia is not confined to a single receptor or neural system, but the interaction of several dysfunctional ones. The especially aggressive nature of schizophrenia leads to a (variable) degree of cerebral tissue loss with each exacerbation of the illness. Understanding schizophrenia as a potentially neurodegenerative disease with neurodevelopmental antecedents may thus be a useful shift in the therapeutic appreciation of this illness. It is essential to remember that psychological and social factors also have neurological consequences: epigenetic influence is one way to understand the psychopathology of these consequences. This is, of course, the rationale for holistic treatment of the illness generally. The wide-ranging pathology of schizophrenia means that holistic management of it will always be required and the concentration on a single pathological pathway is one which both leads researchers to unrewarding conclusions and results in an unsatisfactory outcome for the person who suffers from schizophrenia. Successful management of this illness is therefore always holistic, including the maintenance of appropriate suitable medication as well as psychological and social interventions which are recovery focussed. A thorough understanding of all of the factors involved in schizophrenic illness therefore narrows the translational gap.

Mind the Gap: bridging the translational gap in the management of schizophrenia by treating the whole person.