We are all living with a strange paradox: while the public often seems to know less and less about more and more, many experts know more and more about less and less. Nowhere is this more true than in disorders of mood. As in many fields, there is a burning need for people who can organize, contextualize and make sense of the ever-increasing avalanche of new information. There are few who can do this well, and the authors of this excellent book are superbly equipped to carry out this daunting task.The authors are well-known in the psychiatric community, and here they ask many exceedingly important questions and even answer quite a few of them. For example, why does depression have such a devastating impact on people recovering from a myocardial infarction? Moreover, why are depressed patients — and their family members — more likely to suffer from cardiovascular and inflammatory diseases? They show themselves well able to take disparate information culled from thousands of research papers and to weave a coherent and exciting new story.At the very beginning of the book the authors set out their stall with brief extract from the project description of the National Institute of Mental Health’s Research Domain Criteria program:“If we assume that the clinical syndromes based on subjective symptoms are unique and unitary disorders, we undercut the power of biology to identify illnesses linked to pathophysiology, and we limit the development of more specific treatments.”They go on to say,“The question of whether major depression exists must surely be one of the most rhetorical ones that ever started a book. If depression doesn’t exist, we wouldn’t be writing a book about it, and you never would have read the question in the first place.”The point here is that depression is not a single entity. People in every culture around the globe have been getting depressed since the beginning of recorded history, and no reputable psychiatrist believes that depression is just some kind of chemical imbalance. Certainly, the authors do not. The authors are subtle thinkers who are making Herculean effects of grounding the physical aspects of the depressions in a psychological and social matrix. They understand that we are dealing with systemic illnesses that may also run in families. For example, cardiovascular and inflammatory problems are far more common in those with depression and also in their first degree relatives. Furthermore, there is a clear bidirectional relationship between physical illness and depression, in that physical illnesses may predispose to the development of depressive symptoms and depressive symptoms may engender physical diseases. They are very clear in describing “depression” as a wide range of interrelated symptoms that can occur as a response to many different kinds of environmental adversity, in effect, a kind of “final common pathway.” What kind of environmental adversity? They examine everything from trauma and abuse to infections and inflammation. Given Chuck Raison’s groundbreaking research, it is not surprising that the authors spend a lot of time unpacking the depression/inflammation story. I would imagine that most experts will be surprised by some of what they have discovered.The amount of detail is breathtaking, and the synthesis is highly refreshing. The book is not only bold, but I would also say that it is brave, because the authors stick their necks out repeatedly. My only (minor) criticism is that parts of the book could have been a little more user-friendly. A few more diagrams and page breaks would have been helpful.There is no question that this is the most comprehensive book yet on the biological problems associated with depressive symptoms. So here’s the question, “Well that’s all well and good, but is any of this actually going to move the needle in terms of treatment?”The answer to that is, “Probably.” Because there is always a big difference in terms of what we can do for an individual and what we can prove in clinical trials. Let me give a very simple example. If we look only at pharmacological treatments, there are around 25,000 potential combinations that could be used for treating depressive symptoms. There is an unknown number of other approaches that may target the underlying problems. Doing clinical trials on every one of them would clearly be impractical, so sometimes clinicians have to use every piece of knowledge and know-how, based on a deep understanding of the data, to be able to help an individual. The authors give some examples of individuals diagnosed with depression, in whom they use their approaches to dissect the problems and show their reasoning. This approach will be familiar to every expert who consults on people who have proven difficult to treat.Just today I recommended the book to a group of psychiatric practitioners, but with the caveat that this is not a book for the novice. I have seen criticisms that it is full of jargon. I would respond by saying that it is it not jargon, but it IS technical. And that is inevitable in any book that is mapping out new territory. It used to be said that a medical student would have to learn around six thousand new words in the course of their training. And that can make it challenging to translate material into everyday language. Also it is more than that. It is not just a matter of understanding the words; it is more a matter of the concepts to which they are attached.This is not just a book for today. As ever more information appears in the years to come, it will be invaluable to practitioners to have a firm basis to which the new information can be added.I really wish that everybody treating people with depressive symptoms read this book: it will give them a great deal of food for thought that can be translated into novel treatment strategies.For anyone who really wants to help suffering people, and is prepared to put in a little bit of effort, I highly recommend this book.