Madness in the garden or worm in the apple

The Madness of Adam and Eve: How Schizophrenia Shaped Humanityby David Horrobin, Bantam Press, 2001. £18.99 (281 pages) ISBN 0 593 04649 8As its title implies, this book by David Horrobin, seeks to trace the roots of schizophrenia to the evolution of humanity. The Madness of Adam and Eve book advances two independent but interrelated hypotheses: first, that vulnerability to schizophrenia is an important feature distinguishing Homo sapiens from other primates, and second, that a species-specific requirement for essential fatty acids is at the heart of the condition. The link between the two hypotheses is the increased body fat of humans as compared with non-human primates. The title Adam and Eve is well chosen because it evokes images of both original sin and nakedness. It also ties the book firmly to the out-of-Africa genetic studies of the past decade that have identified the earliest common ancestors of all modern humans.According to the theory put forth in the book, the early years of the Homo sapiens lineage involved a protracted battle for dominance with other highly evolved primates, particularly Homo neanderthalensis. This book claims that the genetic Adam and Eve whose children went on to conquer the world were the first to develop a particular set of genetic mutations, and that the traits that propelled them to eventual victory – creativity and a touch of paranoia – were also those that sowed the seeds of schizophrenia. The fact that rates of schizophrenia are similar throughout the world is taken as evidence that vulnerability to the disorder arose early in the course of Homo sapiens evolution. There is, of course, no way of proving or disproving this theory, given the absence of Neanderthals and Australopithecines to interview.An important component of this theory is that the propensity to schizophrenia must be beneficial to the individuals who suffer from it, or to their relatives, or to society at large. It is, of course, emotionally appealing to suppose that there is a silver lining to the cloud of schizophrenia. However, similar arguments are not made for other neurodevelopmental or neurodegenerative disorders such as mental retardation, Alzheimer's disease, epilepsy, or amyotrophic lateral sclerosis (ALS). It is therefore important that the basis for the claim be scrutinized carefully. The book states that ‘a few schizophrenic individuals themselves, but many first-, second-, and third-degree relatives who share part of the schizophrenic genome, are some of the highest-achieving and most creative individuals around.’ However, the only statistical support for this comes from studies of bipolar disorder, not schizophrenia.Some anecdotal support is presented, such as the fact that John Nash, a Nobel laureate in economics and the subject of the book and film A Beautiful Mind, suffers from schizophrenia. However, the rate of schizophrenia in the general population is 0.5–1.0%. Several hundred Nobel prizes have been awarded over the past century. There is no evidence that the number of Nobel laureates with schizophrenia exceeds the number that would have been expected based upon statistics alone. Lou Gehrig, Jacob Javits and Stephen Hawking all suffered or suffer from ALS. However, one would not attribute their athletic, political or scientific prowess to that disorder.For some disadvantageous conditions, such as sickle-cell anemia, one must argue that the genes are maintained in the gene pool because of heterozygote advantage. However, penetrance of schizophrenia is low (identical twins have a 50% discordance rate), so that involved genes may remain in the gene pool without needing to confer advantage to genetic carriers.The most important and provocative aspect of The Madness of Adam and Eve is the claim that schizophrenia might result from a deficiency of essential fatty acids (EFA), and that treatment with omega-3 fatty acids, in particular, might produce significant clinical improvement. Even if all the evolutionary and sociological arguments put forward in the book were incorrect, development of a new treatment for schizophrenia would be a significant achievement. The usual route for announcing such a development is in a peer-reviewed medical journal following completion of a large, multicenter randomized clinical trial. In the case of EFAs, the number of trials remains small and results have not been entirely consistent. Results at the P<0.05 significance level, especially in small scale studies, can (and do) occur 5% of the time. One large, placebo-controlled study attempting to replicate Horrobin's findings did not find significant benefit from EFA treatment [1xA placebo-controlled trial of omega-3 fatty acid (ethyl-EPA) supplementation for residual symptoms and cognitive impairment in schizophrenia. Fenton, W.S et al. Am. J. Psychiatry. 2001; 158: 2071–2074CrossRef | PubMed | Scopus (168)See all References][1]. Thus, the jury is still out. The book is motivated, in part, by the author's view that his research has not received sufficient support from the medical community. The first chapter of the book warns about how an overly conformist establishment stifles the march of science. However, statements such as ‘we can be confident already that this is the beginning of a revolution – a true paradigm shift in our understanding and management of the condition’ should probably be based upon more than 30 patients’ worth of data.Despite its limitations, the book is entertainingly and clearly written. It argues its points forcefully and covers a large amount of territory. It attempts to place schizophrenia in social and evolutionary context. Whether its theories will turn out to be correct remains an open question. Over the centuries, many theories have been proposed to account for the origins of madness. This book provides yet one more.This review also appeared in Trends in Neurosciences.