Neurobiology of depression,

It is interesting times to produce a comprehensive book in psychiatry: we are witnessing very rapid development in methods to study the nervous system at several levels of organisation from molecular to the whole living brain, and, at the very same time, an increasing discontent with the products of the psychopharmacological revolution of the second half of the previous century that remains the main option to treat diseases of the brain (euphemistically named psychiatric disorders). While one or more chapters on neurobiology of depression have been included in a number of recent books on neuroscience, a book summarising the knowledge on neurobiology of depression had remained an unmet need. Neurobiology of Depression consists of 22 chapters, these being preceded by a foreword by Dr Herman van Praag. The first chapter is devoted to animal models of depression. Chapter 2 essentially describes the role of EEG in clinical depression research, introducing the advances in technology. Chapter 3 highlights the role of the amygdala, hippocampus, subgenual anterior cingulate cortex, dorsolateral prefrontal cortex and ventral striatum in depression. The strategy of genetic neuroimaging in depression is very clearly outlined in Chapter 4, and the available data concisely summarised. Chapter 5 is concerned with the molecular basis of differentiation and development of serotonin-, noradren- and dopaminergic neurons. Chpater 6 presents an interesting historical account of some important steps in psychopharmacological drug development. While condensation of the subject that the CINP History Committee has been covering in a number of separate volumes into a single chapter has generally been successful, the reader interested in the past should be aware that some discovery stories also have other versions. For example, the first patent to a serotonin selective reuptake inhibitor (SSRI), zimelidine, developed by Hans Corrodi, Peder Bengtsson and Arvid Carlsson, was already published in 1972, at the time the Lilly group started to experiment with fluoxetine. And naturally Lapin and Oxenkrug did not postulate the serotonergic theory of depression in 1970 as the reference to this theory is of 1969. (The authors themselves have mentioned elsewhere that it took a couple of years to obtain permission from their national authorities to send the manuscript to ‘The Lancet’.)

Subsequent chapters are devoted to specific neurotransmitters and neuromodulators. Chapters 7 and 8 present overviews of what is known of the contribution of serotonin and noradrenaline, respectively, to depression. A chapter on dopamine might have brought additional value given the structure of the book, as separate overviews follow on glutamate (Chapter 9), endocannabinoids (Chapter 10), opioids (Chapter 11), corticotropin-releasing factor (Chapter 13), tachykinins (Chapter 15), neuropeptide Y (Chapter 16) and nitric oxide (Chapter 17). Neurotrophic factors are represented by the brain-derived neurotrophic factor (Chapter 19). Chapter 12 reviews the neurobiology of biological rhythms and melatonin, and Chapter 14 discusses the possible role of cytokines in depression. Down the intracellular signal transduction cascades, the significance of beta-arrestins and cyclic nucleotide phosphodiesterases is discussed in Chapters 18 and 20, respectively. Chapter 21 is devoted to vascular depression and Chapter 22 attempts to summarise all the previous pieces in order to predict the future drug development.

The editors should certainly be commended for having successfully persuaded several key scientists to contribute chapters to the book and producing such a comprehensive overview of what is known of depression. One might, however, have wished an even more rigorous editorial work: while the typographical errors are strikingly rare (an exception is the repeated wrong spelling of dipeptidyl peptidase), the text of some authors would have become even easier to read after language editing. Furthermore, even though this might be a bit too much to expect, some contrasts between chapters could have been smoothened out. For example, the messages of caution of Chapter 1 on animal models are not congruent with much of the simplistic listing of findings obtained with antidepressant drug screening tests in several of the chapters that follow. A strong side of Neurobiology of Depression is emphasis on including figures, as several are of good generalisation value. (The use of colour figures printed together on a few pages without legends nearby is less convenient.) By bibliographic information, it is a book of year 2012 but infrequently, a reference is made to anything published in 2010. For the best of the chapters, thorough historical introduction and excellent organisation of material compensate well for the absence of the most recent information, especially as the main value of a book cannot be in being current; nevertheless, in a few chapters, recent important findings can be felt missing.

Thus, this book makes a good reference source. Does it deliver synergy? In a way yes, given that a large body of information on the neurobiology of depression has been collected, and in a few chapters, truly insightful comments are there to meet the reader. And yet, if the reader would instead of focussing on the favourite themes decide to read the book from cover to cover as the reviewer was obviously expected to do, a vague aftertaste may emerge that the whole is not larger than its parts. What else this reviewer would have loved to find in a comprehensive book on depression neurobiology were a more systematic approach to address the ‘hard questions' of depression we all know, and attention to pathogenetic development. With the present structure, translation between different approaches and their integration remain difficult to achieve. A quote from the text, ‘it is interesting to note here that in contrast to animal studies, a considerable number of depressed subjects are refractory to any antidepressant treatments', is telling. Indeed, such high expectations may arise exactly because of inclusion of the foreword by van Praag (that, almost symbolically, remains outside the paginated main body of the volume). The foreword calls for a paradigmatic change in how we approach depression and suggests a more refined interpretation of the symptoms and the pathological process behind, termed by the author as ‘functionalisation and verticalisation', in order to be able to understand the aspects of psychiatric vulnerability that cut across many diagnostic entities, and to make sense of the hierarchical organisation of the features of depression and their dynamic and sequential nature. Dr van Praag herewith reminds to those on quest for the neurobiology of depression that ‘between subjects and, over time, within subjects, the appearance of psychiatric syndromes will thus be as variable as the shape of clouds in the sky'. After reading of these thoughts one inevitably will indulge in a dream of a future book that, as a succession to this one that brought the many facts together, will structure the universe of the neurobiology of depression in manner that would provoke creative thinking of both clinicians and researchers on new strategies of making use of biomarkers for the diagnosis or selecting novel leads for drug targets. Meanwhile, this volume can be helpful to many students and professionals interested in depression who wish to extend their as yet narrow expertise to other neurobiological domains.