Peter Kramer describes the science of resilience in his fascinating book, “Against Depression.” His dream–the fantasy of resilience–gives me great hope that one day I might not have to work so hard at staying positive and sane, that I will, more days than not, think about coffee the first thing in the morning.
I’ve excerpted part of his chapter on resilience. There is a lot of technical language in here, but I think this passage will help my Beyond Blue readers to know that their condition is not make-believe, and that science is on our side.

What is to be done to fulfill the fantasy of resilience? The answer would seem simple: everything. . . . But attempts to prevent depression through social or general medical interventions have their limitations. Some people are born with a marked predisposition to depression. For them, routine levels of stress will prove excessive. Even for people who are not especially fragile, there are just too many pathways to mood disorders. Often, societal change is slow; and the swing of the pendulum is not always in the right direction—we can easily imagine life getting more stressful rather than less.

If you had to specify one direct response to the modern understanding of depression, it would be an effort to devise general tools that interrupt the pathway leading from stress to brain injury. The interventions would afford protection to neurons at risk, even for people in adverse social environments. Ideal treatments would catalyze repair and new cell growth.
This goal has, in fact, driven the psychiatric research of the past decade.
For the last fifty years, pharmacologists have worked on modulating the brain’s handling of norepinephrine and serotonin. The results have been disappointing. New medications like Prozac and Paxil and the others have their advantages—they do especially well, for example, with social anxiety, and they have improved the treatment of low-level depression. But the early antidepressants, developed in the 1950s, are as effective at ending depressive episodes.

Besides, throughout that half century, scientists have understood that serotonin and norepinephrine play at best supporting roles in the biology of mood and mood disorder. Research into stress hormones has been a refreshing alternative. It builds on a substaintial knowledge base—decades of studies of endocrine diseases, stroke, and aging. And it holds the promise of prevention, even in the absence of complete knowledge about the nature of depression. . . . .
The gross approach to the stress hormone system—shut it down—may lead to useful treatments for mood disorders. But researchers hoped to craft finer interventions. Perhaps it would be possible to alter the brain’s response to the stress hormones without harming the body’s overall ability to respond to acute challenges. By 1990, the cutting edge of research had moved from modulation of serotonin to the selective blockade of the brain effects of stress hormones. The prime target was corticotropin releasing factor, or CRF.
Corticotropin releasing factor was characterized half a century ago as a hormone that causes the adrenal gland to produce other stress hormones. But CRF has a second set of functions—it acts directly in the nervous system. In a variety of animals, if you introduce CRF into the brain, or if you create a genetically altered individual that produces excess CRF, you see behaviors that look like depression. A number of research results pointed to CRF as a suitable target for intervention in humans. Depressed (human) patients often have elevated levels of CRF in the spinal fluid, a marker of excess CRF in the brain. Studies of untreated depressed patients at autopsy found a tripling of CRF-secreting brain cells, in a pattern suggesting that neurons that normally do not produce CRF had been transformed to do so. Many of the (deleterious) brain effects that we have attributed to stress hormones are put into action by CRF. . . .

Six pharmaceutical houses have patented compounds that block the effects of CRF. In lower mammals, these drugs pass into the brain and block the effects of stressors that otherwise produce depression-like syndromes. Barring disaster—and disasters (suicidality, liver damage) have been common in research on CRF antagonists—the day will come when we get to see these substances in action, in the treatment or prevention of depression in humans.
In the meanwhile, some research teams are shooting the moon. Robert Sapolsky, in particular, is pushing science to its limits. He is using genetic engineering to moderate the effects of stress hormones on the brain. . . .
Sapolsky’s work involves altering neurons so that, when stressed, they make substances that guard again cell death. Sapolsky begins with genes that manufacture neuroprotectants. He attaches these genes to viruses and lets the viruses carry the genes into the neuron. . . .
Sapolsky is engineering an increasingly complex means of fighting brain injury. For instance, he has created a molecule that looks like a stress hormone receptor on one end and like estrogen on the other. In the rat model under study, estrogen causes repair through the growth of new neurons and through arborization. Now when a stressor comes along, the rat brain produces this dual-purpose molecule. The “rear end” of the molecule soaks up stress hormones. And then the “front end” sets repair processes in motion. The more stress it encounters (this is the theory), the more resilient the rat becomes.

Sapolsky is well aware that his model might equally be used to protect the mammalian brain against the causes and consequences of depression. He is extending his research to look at neuroprotection in mental illness. . . .
The Sapolsky work allows us to imagine a future in which depressive patients, or people with a pronounced liability to depression, might be protected through the insertion of genes that, at critical moments, would kick in to prevent cell damage and promote resilience. The result might be, if not the extirpation of depression, then a dramatic interruption of its progression. When you came to adulthood, you might choose to adopt neuroprotective or resilience-inducing genes. Thereafter, your level of depression would not worsen, even in the face of dramatic stresses and humiliating losses. The vascular depression of old age might be delayed. Depression would be ever less common; in the fact of a single bad episode, preventive measures would be employed, to prevent recurrence. . . .
The beauty in this fantasy, the fantasy of resilience, is that it takes place at the level of anatomical pathology, the level of vulnerable cells in selected regions of the brain. A gene is inserted that remains dormant most of the time. Only in the face of stress is it activated—and even then, after a time lag. The brain’s reaction to transient stressors is unchanged; the stress-response “switch” works as it always has, permitting emotion in the face of challenges. It is only when stress threatens to overwhelm and injure neurons that the altered cells produce neuroprotective factors. Protecting neurons should also protect the stress-response switch.
In this model, you are who you are most of the time—glum or perky, empathetic or clueless. You may experience unease, anxiety, alienation, and despair. But even after a humiliating loss, your stress switch will not stay stuck in the “on” position. In due course—and before they shrink your hippocampus or disrupt your prefrontal cortex—your stress hormones will abate. They will not take you farther down the road to chronic depression.