One clinical implication will be addressed as the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is developed. In addition to diagnostic categories at the syndrome level, domains of pathology will be addressed as essential to the evaluation of individuals and to identifying pathology domains to be addressed therapeutically. A parallel system of diagnostic categories and psychopathological dimensions will shift attention to each individual's specific areas of dysfunction without losing the value of syndrome categories. Regulatory agencies will accept domains of pathology as potential indications for drug therapy. Consensus on clinical trial designs - necessary to establish efficacy for impaired cognition or negative symptoms in schizophrenia - has been established, at least for the US Food and Drug Administration (FDA). This shifts drugs discovery in schizophrenia from producing dopamine antagonists for psychosis to novel discoveries for other key domains (apart from dopamine antagonism). Drugs with efficacy in impaired cognition and negative symptoms may have application across a number of disease classes. As these pathologies are observed prior to psychosis, it will raise the possibility of very early intervention and secondary prevention (Carpenter & Koenig, 2008). Furthermore, this shift in paradigm will influence virtually every aspect of schizophrenia research. Genetic studies, for example, will shift from the genetics of schizophrenia as a syndrome to the genetics of pathological domains. This may help clarify the apparent genetic overlap between major illness syndromes. It may be that persons with depression and psychosis share genetic vulnerability for depression with persons who have depression without psychosis. Similarly, mood disordered patients with psychosis may share vulnerability genes for psychosis with persons with schizophrenia. Finally, pathophysiology of cognitive impairment is likely to be shared among impaired individuals in several syndromes rather than being unique to each.
Conclusion
Rather than being a homogeneous disease entity, schizophrenia is characterised by separate domains of pathology, which are only loosely linked with each other.
The loss of precious human experiences and the association with poor long-term functional outcome justifies a focused and dedicated effort to discover the causes and treatments of the deficit syndrome as a distinctive feature of schizophrenia.
In future schizophrenia research, the focus of therapeutic study will move away from schizophrenia as a disease entity onto specific domains of pathology, promoting the development of targeted drug therapies. To understand genetic causation, genetic studies will shift from the genetics of schizophrenia as a syndrome to the genetics of pathological domains.
As a consequence, drugs discovery in schizophrenia redeploys interests from producing dopamine antagonists for psychosis to novel discoveries targeting with new molecular targets and therapeutic profile.
As certain schizophrenia pathologies such as impaired cognition and negative symptoms are observed prior to psychosis, drugs with efficacy in these domains will raise the possibility of very early intervention and secondary prevention. This may substantially improve the quality of life for patients in the near future, and prepare the field to address recovery, cure and prevention.
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