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EDITORIAL

Chaos in Psychiatry

At the 1992 meeting of the Society of Biological Psychiatry I had the opportunity to hear or view the 458 lectures and posters presented. The fertility, enthusiasm, and inventiveness of the members of the society were apparent in this torrent of fascinating new data. Yet time after time I was struck by the conclusion: "We don't know what these findings mean." This agnosia appeared at all levels, from the second messenger activation of genes to the molecalar interactions of transmitters and modulators, and from the networks of neurons within and between cortical and subcortical structures to the developmental sequences of signs and symptoms in behavior. At the lectures the stronger and more experienced investigators presented their cumulative data in diagrams that contained multiple boxes interconnected with arrows. The diagrams flashed by with an average halflife of less than a minute on the screen, with no real possibility for viewers to absorb any more than one bold impression: complexity! What psychiatrists do not always realize is that these diagrams do not represent systems, only their parts and connections. They are like the parts of a toy plane that come in a box and must be assembled in order to fly. When just two pa~ts that are well-known in isolation are interconnected, each to give input to the other, the performance of the coupled unit cannot be predicted, but it can be evaluated by trial and error. Multiple parts cause too much complexity to be comprehended that way. We require the help of concepts taken from dynamics. Those are what enabled the Wright brothers to fly their device. But most psychiatrists do not know what dynamics is. Psychiatric practitioners in particular are not strangers to complexity, because they must connect data across all levels from genes to maladaptive behaviors in their daily management of the mentally ill. What few of them realize is that powerful new tools are at hand that are designed to deal with complexity. Those tools come in the portmanteau called dynamics. As the science of change with time, dynamics is the essence of psychiatry. In seminal monographs and major textbooks by Spencer, Darwin, Jackson, Freud, and others, the introductory chapters show that psychiatry and neurology were both founded on 19thcentury Newtonian dynamics. This foundation became implicit early in the 20th century, perhaps largely because further progress in dynamics was blocked about 1900, when Poincare discovered mathematical chaos but drew a curtain across it as obscenely and unmanageably complex. Computer technology has overcome that block, and new tools for organizing, reducing, displaying, and comprehending complexity, nonlinearity, and chaos are now undergoing rapid development and deployment. They can be tailor-made for managing the mire of data that threatens to encumber further progress in psychiatry. Who will use them? There are many bioengineers and computer scientists who want to do this work, and there is no shortage of medical students and residents who grew up in the Information Age and are adept in its technologies. The difficulty lies not in learning © 1992 Society of Biological Psychiatry

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to use the tools. It lies in restructuring the bioiogic~ data and the ca~riments by which the data are obtained so that the tools can be applied. The locus and the degree of this difficulty should not be misconstrued. Here now comes my message. Senior research supervisors should acknowledge the magnitude of the data overload and the necessity for using dynamics to direct new research so as to organize the complexity. They should recruit, encourage, and protect junior investigators to carry out the task. They should e x a c t that i~itial results will seem simplistic, "proving the obvious," or else unintelligible and even distasteful. Two to five years of sustained application is needed for the acquisition of "good taste" by either the student or the teacher. While not prodding them for quick fixes, supervisors should ride herd on their investigators by asking them, "What does this variable in your equations represent?" and "What (gene, synapse, tract, interaction) does that parameter signify?" Model builders have their own disease, which is known as lucubration, and they should not be left unattended. They are prone to dig intellectual holes into which they disappear. Further, the builders should not be asked: "Is your model true?" Models are not true or false, merely useful or misleading, and they do not prove things but interrelate them. Builders should be asked: "How does your model combine our data?," and "What does it tell us to do next?" What other recourse does psychiatry have, to surmount the present and continuing explosion in its data? Something must be done, because sooner or later empirical researchers tire, retire, or lose their grants. Our libraries are filled with volumes of old research results from played out areas, which no one consults or remembers. There are reams of data on cerebrospinal fluid (CSF) and plasma metabolites; urinary excreta; electroencephalographic (EEG) asymmetries; evoked potential peaks and troughs; brain lesions, cortical, electrical, and chemical stimulation; unit recording; and a dozen other activities. The data were expensive to obtain and now are not worth replicating or even retrieving, because there wa~ little or no theory to specify what to measure, in what ancillary conditions, and with what expected outcomes. This is not the kind of chaos of which we can be proud. Consider that the concentration of each z~eurotransmitter is controlled by feedback through receptors to coordinate the rates of uptake and degradation with the rates of release. The enzymes that perform the tasks of assembly, release, recycling, and degradation are themselves subject to feedback regulation through second messengers and the genome. The set points for the concentrations are subject to modification under feedback controls through various brain systems. The effectiveness of each transmitter by which its concentration is assayed is subject to interaction with other transmitters. Every cortical synapse is embedded in neural networks that oscillate, which neuromuscular synapses usually do not do. Investigators are foolhardy to continue working in this jungle with only the tools of Otto Loewi and Sir Henry Dale, when better resources are at hand. The making of brain theory has its own requirements for review and evaluation, in order that it establish and maintain high st~,.,a~.~rd~.~f performance among its practitioners. The staff members of the National Institute of Mental Health are well aware of the opportunities for new applications of dynamics' in psychiatry and have recently created a Study Section for Computational Neuroscience. This can be a valuable tool in itself in the search for excellence. Research administrators should direct their qualified investigators to that source of funding and should give the moral support that the enterprise will

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need in order for it to succeed. The work will not be easy, but the gains are potentially very large. Let deans, and chairs in psychiatry take note.

Walter Freeman Department of Molecular and Cell Biology University of California Berkeley, CA 94720

Chaos in psychiatry.

BIOL PSYCHIATRY 1992;31:1079-1081 1079 EDITORIAL Chaos in Psychiatry At the 1992 meeting of the Society of Biological Psychiatry I had the opportu...
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