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

Lawrie et al’s paper focuses on reliable diagnostic tools, early diagnosis and prediction of response to pharmacological 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 important but not sufficient, since the diagnosis itself and in particular early diagnosis leaves the clinician with many open questions as to prognosis and the appropriate treatment of the individual patient. Furthermore, to limit the consideration of treatment prediction to the response to pharmacological treatment may be reductive. Finally, even psychiatrists working in clinical practice are asked almost every day by patients, relatives 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 etiopathophysiology of this human condition. 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, social impairment and treatment may vary enormously between patients. Knowledge about this heterogeneity is still very limited, but is of paramount interest for the clinician and therefore deserves particular attention even if empirical studies are still scarce and inconclusive. For instance, several clinical and biological similarities of catatonia with motor disorders and obsessive compulsive disorder have been identified, which point to common pathophysiological mechanisms 1. In brief remitting psychoses, hints to a distinct pathophysiology have been found 2,3. These new pathophysiological findings are relevant for the definition of the diagnostic categories and therefore of direct clinical interest.

In the last decade, important and empirically validated non-pharmacological techniques have been developed, which are linked to pathophysiological hypotheses. 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 pathophysiological mechanism revealed by biological research: the evidence on the role of the components of the left hemispheric language system in the generation of auditory verbal hallucinations has led to the development of fMRI-guided transcranial magnetic stimulation of left temporal brain regions for their treatment 7,8,9.

The question of the origin of schizophrenia still remains open. The practically endless catalogue of findings in various fields, from humanities to empirical 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 dysregulation, another as a genetic deficit, one more as a consequence of an information overflow and the next as a product of social environment. There is urgent need to search for and discuss unifying theories of schizophrenia pathophysiology, which may allow connecting the findings at the various methodological levels, and help us to understand the heterogeneity of the disorder. The situation 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 schizophrenia suffer from structural and functional disorders of modules of the left hemispheric language system, including the primary auditory cortex, the superior posterior temporal lobe and the arcuate fascicle 10,11,12. For the understanding of schizophrenia as a clinical entity, this has a double meaning. First, some symptoms like incoherence, alogia and auditory 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 cognitive 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 pathophysiological mechanisms that may cause phenomena like delusions of existential threat or the motor phenomena of catatonia 13,14.

In conclusion, in addition to the important questions summarized by Lawrie et al, we emphasize the clinical importance of some pathophysiological findings and hypotheses for the development of valid taxonomies, of non-pharmacological interventions, and of comprehensive models for the group of schizophrenias.