Clinical handling and understanding of schizophrenia should be based on pathophysiological findings and theories

Abstract

Lawrie et al’s paper focuses on reli-able diagnostic tools, early diagnosis and prediction of response to pharma-cological treatment in schizophrenia, providing a very useful overview of the existing evidence. However, achieving a reliable and early diagnosis of schizophrenia with clinical and biological methods is im-portant but not sufficient, since the di-agnosis itself and in particular early di-agnosis leaves the clinician with many open questions as to prognosis and the appropriate treatment of the individual patient. Furthermore, to limit the con-sideration of treatment prediction to the response to pharmacological treatment may be reductive. Finally, even psychia-trists working in clinical practice are asked almost every day by patients, rela -tives or friends to explain schizophrenia. Therefore, even if the clinician is not a scientist or philosopher, he will be very interested to know what to respond to this question which refers to the etio-pathophysiology of this human condi-tion. In the following, I will briefly touch these points. The diagnosis of schizophrenia is polythetic. It is possible that two patients with the same diagnosis do not share even one symptom. Further, course, so-cial impairment and treatment may vary enormously between patients. Knowl-edge about this heterogeneity is still very limited, but is of paramount interest for the clinician and therefore deserves par -ticular attention even if empirical stud-ies are still scarce and inconclusive. For instance, several clinical and biological similarities of catatonia with motor dis-orders and obsessive compulsive disor-der have been identified, which point to common pathophysiological mecha-nisms (1). In brief remitting psychoses, hints to a distinct pathophysiology have been found (2,3). These new pathophys -iological findings are relevant for the definition of the diagnostic categories and therefore of direct clinical interest. In the last decade, important and em -pirically validated non-pharmacological techniques have been developed, which are linked to pathophysiological hy-potheses. For instance, standardized diagnostic batteries (4) and detailed neurocognitive interventions (5,6) have been developed following hypotheses inspired by neuropsychological findings. There is also an example of an efficacious therapy derived from a pathophysiologi -cal mechanism revealed by biological re -search: the evidence on the role of the components of the left hemispheric lan-guage system in the generation of audi-tory verbal hallucinations has led to the development of fMRI-guided transcrani -al magnetic stimulation of left temporal brain regions for their treatment (7-9). The question of the origin of schizo-phrenia still remains open. The practi-cally endless catalogue of findings in various fields, from humanities to empir -ical psychology, systems physiology and molecular biology, does not match the needs of clinicians to give their patients a useful model of their condition. People will lose confidence in our discipline, if one psychiatrist explains the disorder as caused by a transmitter dysregula-tion, another as a genetic deficit, one more as a consequence of an informa-tion overflow and the next as a product of social environment. There is urgent need to search for and discuss unifying theories of schizophrenia pathophysiol-ogy, which may allow connecting the findings at the various methodological levels, and help us to understand the heterogeneity of the disorder. The situa-tion is not as desperate as it seems, since there are recent developments which deserve attention. For instance, there are several indications that part of our patients with the diagnosis of schizo-phrenia suffer from structural and func-tional disorders of modules of the left hemispheric language system, including the primary auditory cortex, the superior posterior temporal lobe and the arcuate fascicle (10-12). For the understanding of schizophrenia as a clinical entity, this has a double meaning. First, some symp -toms like incoherence, alogia and audi-tory hallucinations are linked to subtle structural changes of the cerebral cortex and to chronic or episodic functional dysregulation of language production and perception. A simple but important implication for therapy and clinical handling of these patients is the need to adapt standard colloquial and cogni-tive therapies to the verbal capacities of these patients. The second meaning of these findings is the inverse conclusion, i.e. that not all schizophrenic patients have deficits in their language functions. There are probably other pathophysi-