Depression is the flaw in love. To be creatures who love, we must be creatures who can despair at what we lose, and depression is the mechanism of that despair. When it comes, it degrades one’s self and ultimately eclipses the capacity to give or receive affection. It is the aloneness within us made manifest, and it destroys not only connection to others but also the ability to be peacefully alone with oneself. Love, though it is no prophylactic against depression, is what cushions the mind and protects it from itself. Medications and psychotherapy can renew that protection, making it easier to love and be loved, and that is why they work. In good spirits, some love themselves and some love others and some love work and some love God: any of these passions can furnish that vital sense of purpose that is the opposite of depression. Love forsakes us from time to time, and we forsake love. In depression, the meaninglessness of every enterprise and every emotion, the meaninglessness of life itself, becomes self-evident. The only feeling left in this loveless state is insignificance.

Life is fraught with sorrows: no matter what we do, we will in the end die; we are, each of us, held in the solitude of an autonomous body; time passes, and what has been will never be again. Pain is the first experience of world-helplessness, and it never leaves us. We are angry about being ripped from the comfortable womb, and as soon as that anger fades, distress comes to take its place. Even those people whose faith promises them that this will all be different in the next world cannot help experiencing anguish in this one; Christ himself was the man of sorrows. We live, however, in a time of increasing palliatives; it is easier than ever to decide what to feel and what not to feel. There is less and less unpleasantness that is unavoidable in life, for those with the means to avoid. But despite the enthusiastic claims of pharmaceutical science, depression cannot be wiped out so long as we are creatures conscious of our own selves. It can at best be contained – and containing is all that current treatments for depression aim to do.

Highly politicized rhetoric has blurred the distinction between depression and its consequences – the distinction between how you feel and how you act in response. This is in part a social and medical phenomenon, but it is also the result of linguistic vagary attached to emotional vagary. Perhaps depression can best be described as emotional pain that forces itself on us against our will, and then breaks free of its externals. Depression is not just a lot of pain; but too much pain can compost itself into depression. Grief is depression in proportion to circumstance; depression is grief out of proportion to circumstance. It is tumbleweed distress that thrives on thin air, growing despite its detachment from the nourishing earth. It can be described only in metaphor and allegory. Saint Anthony in the desert, asked how he could differentiate between angels who came to him humble and devils who came in rich disguise, said you could tell by how you felt after they had departed. When an angel left you, you felt strengthened by his presence; when a devil left, you felt horror. Grief is a humble angel who leaves you with strong, clear thoughts and a sense of your own depth. Depression is a demon who leaves you appalled.

Virginia Woolf has written about this state with an eerie clarity: “Jacob went to the window and stood with his hands in his pockets. There he saw three Greeks in kilts; the masts of ships; idle or busy people of the lower classes strolling or stepping out briskly, or falling into groups and gesticulating with their hands. Their lack of concern for him was not the cause of his gloom; but some more profound conviction – it was not that he himself happened to be lonely, but that all people are.” In the same book, Jacob’s Room, she describes how “There rose in her mind a curious sadness, as if time and eternity showed through skirts and waistcoats, and she saw people passing tragically to destruction. Yet, heaven knows, Julia was no fool.” It is this acute awareness of transience and limitation that constitutes mild depression. Mild depression, for many years simply accommodated, is increasingly subject to treatment as doctors scrabble to address its diversity.

Large depression is the stuff of breakdowns. If one imagines a soul of iron that weathers with grief and rusts with mild depression, then major depression is the startling collapse of a whole structure. There are two models for depression: the dimensional and the categorical. The dimensional posits that depression sits on a continuum with sadness and represents an extreme version of something everyone has felt and known. The categorical describes depression as an illness totally separate from other emotions, much as a stomach virus is totally different from acid indigestion. Both are true. You go along the gradual path or the sudden trigger of emotion and then you get to a place that is genuinely different. It takes time for a rusting iron-framed building to collapse, but the rust is ceaselessly powdering the solid, thinning it, eviscerating it. The collapse, no matter how abrupt it may feel, is the cumulative consequence of decay. It is nonetheless a highly dramatic and visibly different event. It is a long time from the first rain to the point when rust has eaten through an iron girder. Sometimes the rusting is at such key points that the collapse seems total, but more often it is partial: this section collapses, knocks that section, shifts the balances in a dramatic way.

It is not pleasant to experience decay, to find yourself exposed to the ravages of an almost daily rain, and to know that you are turning into something feeble, that more and more of you will blow off with the first strong wind, making you less and less. Some people accumulate more emotional rust than others. Depression starts out insipid, fogs the days into a dull color, weakens ordinary actions until their clear shapes are obscured by the effort they require, leaves you tired and bored and self-obsessed – but you can get through all that. Not happily, perhaps, but you can get through. No one has ever been able to define the collapse point that marks major depression, but when you get there, there’s not much mistaking it. Major depression is a birth and a death: it is both the new presence of something and the total disappearance of something. Birth and death are gradual, though official documents may try to pinion natural law by creating categories such as “legally dead” and “time born.” Despite nature’s vagaries, there is definitely a point at which a baby who has not been in the world is in it, and a point at which a pensioner who has been in the world is no longer in it. It’s true that at one stage the baby’s head is here and his body not; that until the umbilical cord is severed the child is physically connected to the mother. It’s true that the pensioner may close his eyes for the last time some hours before he dies, and that there is a gap between when he stops breathing and when he is declared “brain-dead.” Depression exists in time. A patient may say that he has spent certain months suffering major depression, but this is a way of imposing a measurement on the immeasurable. All that one can really say for certain is that one has known major depression, and that one does or does not happen to be experiencing it at any given present moment.

The birth and death that constitute depression occur at once. I returned, not long ago, to a wood in which I had played as a child and saw an oak, a hundred years dignified, in whose shade I used to play with my brother. In twenty years, a huge vine had attached itself to this confident tree and had nearly smothered it. It was hard to say where the tree left off and the vine began. The vine had twisted itself so entirely around the scaffolding of tree branches that its leaves seemed from a distance to be the leaves of the tree; only up close could you see how few living oak branches were left, and how a few desperate little budding sticks of oak stuck like a row of thumbs up the massive trunk, their leaves continuing to photosynthesize in the ignorant way of mechanical biology.

Fresh from a major depression in which I had hardly been able to take on board the idea of other people’s problems, I empathized with that tree. My depression had grown on me as that vine had conquered the oak; it had been a sucking thing that had wrapped itself around me, ugly and more alive than I. It had had a life of its own that bit by bit asphyxiated all of my life out of me. At the worst stage of major depression, I had moods that I knew were not my moods: they belonged to the depression, as surely as the leaves on that tree’s high branches belonged to the vine. When I tried to think clearly about this, I felt that my mind was immured, that it couldn’t expand in any direction. I knew that the sun was rising and setting, but little of its light reached me. I felt myself sagging under what was much stronger than I; first I could not use my ankles, and then I could not control my knees, and then my waist began to break under the strain, and then my shoulders turned in, and in the end I was compacted and fetal, depleted by this thing that was crushing me without holding me. Its tendrils threatened to pulverize my mind and my courage and my stomach, and crack my bones and desiccate my body. It went on glutting itself on me when there seemed nothing left to feed it.

I was not strong enough to stop breathing. I knew then that I could never kill this vine of depression, and so all I wanted was for it to let me die. But it had taken from me the energy I would have needed to kill myself, and it would not kill me. If my trunk was rotting, this thing that fed on it was now too strong to let it fall; it had become an alternative support to what it had destroyed. In the tightest corner of my bed, split and racked by this thing no one else seemed to be able to see, I prayed to a God I had never entirely believed in, and I asked for deliverance. I would have been happy to die the most painful death, though I was too dumbly lethargic even to conceptualize suicide. Every second of being alive hurt me. Because this thing had drained all fluid from me, I could not even cry. My mouth was parched as well. I had thought that when you feel your worst your tears flood, but the very worst pain is the arid pain of total violation that comes after the tears are all used up, the pain that stops up every space through which you once metered the world, or the world, you. This is the presence of major depression.

I have said that depression is both a birth and a death. The vine is what is born. The death is one’s own decay, the cracking of the branches that support this misery. The first thing that goes is happiness. You cannot gain pleasure from anything. That’s famously the cardinal symptom of major depression. But soon other emotions follow happiness into oblivion: sadness as you had known it, the sadness that seemed to have led you here; your sense of humor; your belief in and capacity for love. Your mind is leached until you seem dim-witted even to yourself. If your hair has always been thin, it seems thinner; if you have always had bad skin, it gets worse. You smell sour even to yourself. You lose the ability to trust anyone, to be touched, to grieve. Eventually, you are simply absent from yourself.

Maybe what is present usurps what becomes absent, and maybe the absence of obfuscatory things reveals what is present. Either way, you are less than yourself and in the clutches of something alien. Too often, treatments address only half the problem: they focus only on the presence or only on the absence. It is necessary both to cut away that extra thousand pounds of the vines and to relearn a root system and the techniques of photosynthesis. Drug therapy hacks through the vines. You can feel it happening, how the medication seems to be poisoning the parasite so that bit by bit it withers away. You feel the weight going, feel the way that the branches can recover much of their natural bent. Until you have got rid of the vine, you cannot think about what has been lost. But even with the vine gone, you may still have few leaves and shallow roots, and the rebuilding of your self cannot be achieved with any drugs that now exist. With the weight of the vine gone, little leaves scattered along the tree skeleton become viable for essential nourishment. But this is not a good way to be. It is not a strong way to be. Rebuilding of the self in and after depression requires love, insight, work, and, most of all, time.

Diagnosis is as complex as the illness. Patients ask doctors all the time, “Am I depressed?” as though the result were in a definitive blood test. The only way to find out whether you’re depressed is to listen to and watch yourself, to feel your feelings and then think about them. If you feel bad without reason most of the time, you’re depressed. If you feel bad most of the time with reason, you’re also depressed, though changing the reasons may be a better way forward than leaving circumstance alone and attacking the depression. If the depression is disabling to you, then it’s major. If it’s only mildly distracting, it’s not major. Psychiatry’s bible – the Diagnostic and Statistical Manual, fourth edition (DSM-IV) – ineptly defines depression as the presence of five or more on a list of nine symptoms. The problem with the definition is that it’s entirely arbitrary. There’s no particular reason to qualify five symptoms as constituting depression; four symptoms are more or less depression; and five symptoms are less severe than six. Even one symptom is unpleasant. Having slight versions of all the symptoms may be less of a problem than having severe versions of two symptoms. After enduring diagnosis, most people seek causation, despite the fact that knowing why you are sick has no immediate bearing on treating the sickness.

Illness of the mind is real illness. It can have severe effects on the body. People who show up at the offices of their doctors complaining about stomach cramps are frequently told, “Why, there’s nothing wrong with you except that you’re depressed!” Depression, if it is sufficiently severe to cause stomach cramps, is actually a really bad thing to have wrong with you, and it requires treatment. If you show up complaining that your breathing is troubled, no one says to you, “Why, there’s nothing wrong with you except that you have emphysema!” To the person who is experiencing them, psychosomatic complaints are as real as the stomach cramps of someone with food poisoning. They exist in the unconscious brain, and often enough the brain is sending inappropriate messages to the stomach, so they exist there as well. The diagnosis – whether something is rotten in your stomach or your appendix or your brain – matters in determining treatment and is not trivial. As organs go, the brain is quite an important one, and its malfunctions should be addressed accordingly.

Chemistry is often called on to heal the rift between body and soul. The relief people express when a doctor says their depression is “chemical” is predicated on a belief that there is an integral self that exists across time, and on a fictional divide between the fully occasioned sorrow and the utterly random one. The word chemical seems to assuage the feelings of responsibility people have for the stressed-out discontent of not liking their jobs, worrying about getting old, failing at love, hating their families. There is a pleasant freedom from guilt that has been attached to chemical. If your brain is predisposed to depression, you need not blame yourself for it. Well, blame yourself or evolution, but remember that blame itself can be understood as a chemical process, and that happiness, too, is chemical. Chemistry and biology are not matters that impinge on the “real” self; depression cannot be separated from the person it affects. Treatment does not alleviate a disruption of identity, bringing you back to some kind of normality; it readjusts a multifarious identity, changing in some small degree who you are.

Anyone who has taken high school science classes knows that human beings are made of chemicals and that the study of those chemicals and the structures in which they are configured is called biology. Everything that happens in the brain has chemical manifestations and sources. If you close your eyes and think hard about polar bears, that has a chemical effect on your brain. If you stick to a policy of opposing tax breaks for capital gains, that has a chemical effect on your brain. When you remember some episode from your past, you do so through the complex chemistry of memory. Childhood trauma and subsequent difficulty can alter brain chemistry. Thousands of chemical reactions are involved in deciding to read this book, picking it up with your hands, looking at the shapes of the letters on the page, extracting meaning from those shapes, and having intellectual and emotional responses to what they convey. If time lets you cycle out of a depression and feel better, the chemical changes are no less particular and complex than the ones that are brought about by taking antidepressants. The external determines the internal as much as the internal invents the external. What is so unattractive is the idea that in addition to all other lines being blurred, the boundaries of what makes us ourselves are blurry. There is no essential self that lies pure as a vein of gold under the chaos of experience and chemistry. Anything can be changed, and we must understand the human organism as a sequence of selves that succumb to or choose one another. And yet the language of science, used in training doctors and, increasingly, in nonacademic writing and conversation, is strangely perverse.

The cumulative results of the brain’s chemical effects are not well understood. In the 1989 edition of the standard Comprehensive Textbook of Psychiatry, for example, one finds this helpful formula: a depression score is equivalent to the level of 3-methoxy-4-hydroxyphenylglycol (a compound found in the urine of all people and not apparently affected by depression); minus the level of 3-methoxy-4-hydroxymandelic acid; plus the level of norepinephrine; minus the level of normetanephrine plus the level of metanepherine, the sum of those divided by the level of 3-methoxy-4-hydroxymandelic acid; plus an unspecified conversion variable; or, as CTP puts it: “D-type score = C1 (MHPG) – C2 (VMA) + C3 (NE) – C4 (NMN + MN)/VMA + C0.” The score should come out between one for unipolar and zero for bipolar patients, so if you come up with something else – you’re doing it wrong. How much insight can such formulae offer? How can they possibly apply to something as nebulous as mood? To what extent specific experience has conduced to a particular depression is hard to determine; nor can we explain through what chemistry a person comes to respond to external circumstance with depression; nor can we work out what makes someone essentially depressive.

Although depression is described by the popular press and the pharmaceutical industry as though it were a single-effect illness such as diabetes, it is not. Indeed, it is strikingly dissimilar to diabetes. Diabetics produce insufficient insulin, and diabetes is treated by increasing and stabilizing insulin in the bloodstream. Depression is not the consequence of a reduced level of anything we can now measure. Raising levels of serotonin in the brain triggers a process that eventually helps many depressed people to feel better, but that is not because they have abnormally low levels of serotonin. Furthermore, serotonin does not have immediate salutary effects. You could pump a gallon of serotonin into the brain of a depressed person and it would not in the instant make him feel one iota better, though a long-term sustained raise in serotonin level has some effects that ameliorate depressive symptoms. “I’m depressed but it’s just chemical” is a sentence equivalent to “I’m murderous but it’s just chemical” or “I’m intelligent but it’s just chemical.” Everything about a person is just chemical if one wants to think in those terms. “You can say it’s ‘just chemistry,’ ” says Maggie Robbins, who suffers from manic-depressive illness. “I say there’s nothing ‘just’ about chemistry.” The sun shines brightly and that’s just chemical too, and it’s chemical that rocks are hard, and that the sea is salt, and that certain springtime afternoons carry in their gentle breezes a quality of nostalgia that stirs the heart to longings and imaginings kept dormant by the snows of a long winter. “This serotonin thing,” says David McDowell of Columbia University, “is part of modern neuromythology.” It’s a potent set of stories.

Internal and external reality exist on a continuum. What happens and how you understand it to have happened and how you respond to its happening are usually linked, but no one is predictive of the others. If reality itself is often a relative thing, and the self is in a state of permanent flux, the passage from slight mood to extreme mood is a glissando. Illness, then, is an extreme state of emotion, and one might reasonably describe emotion as a mild form of illness. If we all felt up and great (but not delusionally manic) all the time, we could get more done and might have a happier time on earth, but that idea is creepy and terrifying (though, of course, if we felt up and great all the time we might forget all about creepiness and terror).

Influenza is straightforward: one day you do not have the responsible virus in your system, and another day you do. HIV passes from one person to another in a definable isolated split second. Depression? It’s like trying to come up with clinical parameters for hunger, which affects us all several times a day, but which in its extreme version is a tragedy that kills its victims. Some people need more food than others; some can function under circumstances of dire malnutrition; some grow weak rapidly and collapse in the streets. Similarly, depression hits different people in different ways: some are predisposed to resist or battle through it, while others are helpless in its grip. Willfulness and pride may allow one person to get through a depression that would fell another whose personality is more gentle and acquiescent.

Depression interacts with personality. Some people are brave in the face of depression (during it and afterward) and some are weak. Since personality too has a random edge and a bewildering chemistry, one can write everything off to genetics, but that is too easy. “There is no such thing as a mood gene,” says Steven Hyman, director of the National Institute of Mental Health. “It’s just shorthand for very complex gene-environment interactions.” If everyone has the capacity for some measure of depression under some circumstances, everyone also has the capacity to fight depression to some degree under some circumstances. Often, the fight takes the form of seeking out the treatments that will be most effective in the battle. It involves finding help while you are still strong enough to do so. It involves making the most of the life you have between your most severe episodes. Some horrendously symptom-ridden people are able to achieve real success in life; and some people are utterly destroyed by the mildest forms of the illness.

Working through a mild depression without medications has certain advantages. It gives you the sense that you can correct your own chemical imbalances through the exercise of your own chemical will. Learning to walk across hot coals is also a triumph of the brain over what appears to be the inevitable physical chemistry of pain, and it is a thrilling way to discover the sheer power of mind. Getting through a depression “on your own” allows you to avoid the social discomfort associated with psychiatric medications. It suggests that we are accepting ourselves as we were made, reconstructing ourselves only with our own interior mechanics and without help from the outside. Returning from distress by gradual degrees gives sense to affliction itself.