January 2011
Is It Possible to Explain Complex Mental Disorders at the Biological Level?

Mario Maj
President, World Psychiatric Association
In the February issue of World Psychiatry, we publish a Forum entitled "Do we have any solid evidence of clinical utility about the pathophysiology of schizophrenia?", with an introductory paper by S.M. Lawrie and commentaries by S. Kapur, S.J. Wood, M.J. Owen, M.S. Keshavan, T.D. Cannon, W. Strik and P. Falkai. This follows to the Forum entitled "Pathophysiology of depression: do we have any solid evidence of interest to clinicians?", published in the October 2010 issue of the journal.

These Forums aim to help practising clinicians to orient themselves in the huge mass of data which have accumulated in the past decades concerning the pathophysiology of these two major mental disorders.
It is a fact that the gap between the restricted circle of researchers working in this area and the large population of clinicians dealing with patients worldwide has been constantly increasing over the years. The average psychiatrist does not follow the progress of biological research with the same attention and confidence as the average clinician in the other branches of medicine. He either does not believe at all in that research, or does not expect that research to produce in the near future anything which may be of practical utility for his daily practice. Furthermore, he does not perceive the gradual accumulation of "evidence" as an indication of a continuing increase of "knowledge", but rather as a sign of uncertainty and confusion.

Is there anything, in the mass of biological data on schizophrenia and depression, which promises to become in the foreseeable future of any usefulness for everyday clinical practice? This is the question that the two Forums were expected to address, and the reader will see that the views expressed by the participants are quite different. They can be schematically reconducted to two main positions.

The first position is that we are on the wrong track. This may be because the current characterization of the phenotypes (schizophrenia and depression) is inadequate, or because these conditions are very heterogeneous and largely overlap with each other, or because the biological level at which our current research efforts are being displayed (e.g., neuronal circuits, neurotransmitters) is very far from the one at which a convincing explanation of the disorders is likely to be found; or because brain dysfunctions can only account for a vulnerability to something which emerges at the interface between the brain and the world of interpersonal relationships, so that many different brain dysfunctions can be found in patients with schizophrenia or with depression, but the essence of these disorders cannot be delineated at the biological level.

The second position is that we are on the right track, but we are dealing with conditions that are very complex, much more than those which are the subject of investigation of the other branches of medicine. The functions which are perturbed in schizophrenia and in depression are the most complex of human beings. Most of them involve an interaction between such a composite organ as the brain and the even more composite world of interpersonal relationships in which all of us are immersed. It is not surprising that research is progressing so slowly and that many alternative avenues are being pursued. Our current technology and modeling may not be adequate to address that complexity, and the future may bring out very important advances in this respect. Furthermore, we cannot expect a single model to explain all the constituents of the complex picture of schizophrenia or depression: "decomposing" these disorders in their various elements may be very helpful. On the other hand, the many models which are currently proposed should not be regarded as mutually exclusive: they may address different levels of the complexity and may turn out to be consistent with each other.

Time will tell whether it is possible to explain complex mental disorders at the biological level, or whether biological dysfunctions can only account for various pathways of vulnerability to those disorders, whose identity emerges at a higher level. Meanwhile, these Forums offer to our readers a clear and accessible picture of the ongoing research and the hypotheses which are currently put forward.




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