Manfred's Column, April 2005: From Neurons to Delusions


April 2005

From Neurons to Delusions

From neurons to delusions — to the reader this may sound either like a categorical mistake or like plain exaggeration – or both. Nevertheless, at present it is possible to see connections between the function of neurons on the one hand, and higher cognitive functions and their pathology on the other hand, which even a few years ago were impossible to envision. The study of these connections has transformed psychiatry into one of the most exciting fields of present day research.

What is most exciting about present day psychiatry is the fact that research from a large variety of scientific fields provides its progress with impulse and thrust. The Human Genome Project will undoubtedly provide a marked contribution to our understanding of the heritable aspects of mental disorders. The products of genes, proteins and their function will be discovered and populations of receptors, classes and sub-classes will be identified. Although progress may not be as fast as some had anticipated, the discovery of the blueprint of our genetic code will no doubt lead to noticeable improvements in the diagnosis and treatment of mental disorders.

While geneticists work their way bottom up from molecules to symptoms, their efforts are complemented by cognitive neuroscientists working their way down from higher mental functions to the brain and neuronal mechanisms that underlie these functions. Cognitive neuroscience’s methods range from classical neuropsychological tests and experimental psychological approaches to electrophysiological, and lately, functional neuroimaging techniques.

It is interesting to note that both the human genome project and cognitive neuroscience involve the problem of mapping. For this reason both of these large scale scientific enterprises have been compared: the former seeks to find the map of about one hundred thousand genes, and to specify the loci of specific alleles whose variance may have medical significance, while the latter aims to find the approximately 700 cortical maps, define their function, the code they use and their interactions that bring about mental life and its pathology.

Between the level of single neurons and their genetically determined biochemistry, and the level of systems of interacting cortical maps, is the level of neural networks. This type of analysis has a history of more than half a century, and has its origin at the time neurons were conceived of as units that process information. At present, computational neuroscience, or neuroinformatics (to use the European term), strives to understand how assemblies of neurons carry out such basic functions as pattern recognition, information storage and retrieval, as well as how they guide behaviour (of organisms and how this could advance robotics). Interestingly, there is hardly a symptom, syndrome, or mental disorder for which a neural network model has not been proposed that sheds some light on the nature of the pathology under scrutiny.

Knowledge from neurobiology can thus enter psychiatric reasoning via different levels of analysis, as shall be demonstrated using delusions as a case in point. Acute delusions are likely to be the result of dysfunctional neuromodulation in the dopamine system (and, possibly, other neuromodulatry systems such as the 5HT system and the noradrenergic system as well), which can be studied at the neuronal level. The effects of such a biochemical dysfunction are complex and cannot be understood properly using concepts such as activation or inhibition alone. Even small networks exhibit non-linear behaviour, which is why their workings are best understood by means of computer simulations of their functions. At the cognitive neuroscience level, the effects of dysfunctional biochemistry and micro-network function on higher cognitive functions can be studied experimentally. Even though we do not currently measure the size of a delusional system in square millimetres, the idea of such measurements for diagnostic purposes is no longer as far-fetched as it may have appeared to be just a few years ago.

Even though we currently lack a generally accepted neurobiological theory for delusions, we have an idea of how such a theory may look and which methods we may use to get there. This is the most important progress that has been made in the past few years and it makes psychiatry the most exciting field of medicine.