All Annotations of The Reinvention of the Self: A mind-altering idea reveals how life affects the brain (Seed Magazine)[Preview]

saved by7 people, first byPamela M. on 2006-06-28, last byYule Heibel on 2008-08-13

• The structure of our brain, from the details of our dendrites to the density of our hippocampus, is incredibly influenced by our surroundings. Put a primate under stressful conditions, and its brain begins to starve. It stops creating new cells. The cells it already has retreat inwards. The mind is disfigured.

  
  
  

  The social implications of this research are staggering. If boring environments, stressful noises, and the primate’s particular slot in the dominance hierarchy all shape the architecture of the brain—and Gould’s team has shown that they do—then the playing field isn’t level. Poverty and stress aren’t just an idea: they are an anatomy. Some brains never even have a chance.

• Viewed through the magnified eyes of a confocal microscope, a newborn neuron looks fragile, almost lonely. Everything around it is connected to everything else, but the new cell is all alone, just a seed of soma and a thin stalk of axon desperately trying to plug itself into the network. If it doesn’t, it will die.

• To understand how neurogenesis—the process of creating new brain cells— works, Gould’s lab studies the effect of two separate variables: stress and enriched environments. Chronic stress, predictably enough, decreases neurogenesis. As Christian Mirescu, one of Gould’s post-docs, put it, “When a brain is worried, it’s just thinking about survival. It isn’t interested in investing in new cells for the future.”

  
  
  

  On the other hand, enriched animal environments—enclosures that simulate the complexity of a natural habitat—lead to dramatic increases in both neurogenesis and the density of neuronal dendrites, the branches that connect one neuron to another. Complex surroundings create a complex brain.

• The subject of stress has been the single continuous thread running through Gould’s research career. From the brain’s perspective, stress is primarily signaled by an increase in the bloodstream of a class of steroid called glucocorticoids, which put the body on a heightened state of alert. But glucocorticoids can have one nasty side-effect: They are toxic for the brain. When stress becomes chronic, neurons stop investing in themselves. Neurogenesis ceases. Dendrites disappear. The hippocampus, a part of the brain essential for learning and memory, begins withering away.

  
  
  

  Gould’s insight was that understanding how stress damages the brain could illuminate the general mechanisms—especially neurogenesis—by which the brain is affected by its environ-mental conditions.

• As a general rule of thumb, a rough life—especially a rough start to life—strongly correlates with lower levels of fresh cells

• “Poverty is stress,” she says, with more than a little passion in her voice. “One thing that always strikes me is that when you ask Americans why the poor are poor, they always say it’s because they don’t work hard enough, or don’t want to do better. They act like poverty is a character issue.”

  
  
  

  Gould’s work implies that the symptoms of poverty are not simply states of mind; they actually warp the mind. Because neurons are designed to reflect their circumstances, not to rise above them, the monotonous stress of living in a slum literally limits the brain.

• When Duman began studying the molecular basis of antidepressants back in the early 90s, the first thing he realized was that the serotonin hypothesis made no sense. A competing theory, which was supposed to explain the Prozaz lag, was that antidepressants increase the number of serotonin receptors. However, that theory was also disproved. “It quickly became clear that serotonin wasn’t the whole story,” Duman says. “Our working hypothesis at the time just wasn’t right.”

  
  
  

  But if missing serotonin isn’t the underlying cause of depression, then how do antidepressants work? As millions will attest, Prozac does do something. Duman’s insight, which he began to test gradually, was that a range of antidepressants trigger a molecular pathway that has little, if anything, to do with serotonin. Instead, this chemical cascade leads to an increase in the production of a class of proteins known as trophic factors. Trophic factors make neurons grow. What water and sun do for trees, trophic factors do for brain cells. Depression was like an extended drought: It deprived neurons of the sustenance they need.

• In an influential set of studies, Sapolsky and McEwen had shown that prolonged bouts of stress were devastating to neurons, especially in the hippocampus. In one particularly poignant experiment, male vervet monkeys bullied by their more dominant peers suffered serious and structural brain damage. Furthermore, this neural wound seemed to be caused by a decrease in the same trophic factors that Duman had been studying. From the perspective of the brain, stress and depression produced eerily similar symptoms. They shared a destructive anatomy.
• Nottebohm, in a series of beautiful studies on birds, had showed that neurogenesis was essential to birdsong. To sing their complex melodies, male birds needed new brain cells. In fact, up to 1% of the neurons in the bird’s song center were created anew, every day.
• The mind, far from being stagnant, is actually in a constant state of cellular upheaval. By 1999, even Rakic had admitted that neurogenesis is real. He published a paper in Proceedings of the National Academy of Sciences that reported seeing new neurons in the hippocampus of macaques, an old world primate. The textbooks were rewritten. The brain, Elizabeth Gould had now firmly established, is always giving birth. The self is continually reinventing itself.
• If these pills are successful, they will be definitive proof that antidepressants work by increasing neurogenesis. Depression is not simply the antagonist of happiness. Instead, despair might be caused by the loss of the brain’s essential plasticity. A person’s inability to change herself is what drags her down.

• Though Gould’s lab has thoroughly demonstrated the long-term consequences of deprivation and stress, the brain, like skin, can heal itself, as Gould is now beginning to document, finding hopeful antidotes to neurogenesis-inhibiting injuries. “My hunch is that a lot of these abnormalities [caused by stress] can be fixed in adulthood,” she says. “I think that there’s a lot of evidence for the resiliency of the brain.”

  
  
  

  On a cellular level, the scars of stress can literally be healed by learning new things.

• The realization that typical laboratory conditions are debilitating for animals has been one of the accidental discoveries of the neurogenesis field. Nottebohm, for example, only witnessed neurogenesis in birds because he studied them in their actual habitat. Had he kept his finches and canaries in metal cages, depriving them of their natural social context, he would never have observed such an abundance of new cells. The birds would have been too stressed to sing. As Nottebohm has said, “Take nature away and all your insight is in a biological vacuum.”
• The mind is like a muscle: it swells with exercise. Gould’s and Kozorovitskiy’s work reminds us not only how easy it is to hurt a brain, but how little it takes for that brain to heal.
• Rakic

• Duman likes to talk with his feet propped up on his desk. He speaks with the quiet confidence of someone whose ideas once seemed far-fetched but are finally being confirmed.

  
  
  

  “Even as a graduate student,” Duman says, “I was fascinated by how antidepressants work. I always thought that if I can just figure out their mechanism of action—and identify why there is this time-delay in their effect—then I will have had a productive career.”

• After her wearisome post-doc, during which her data was continually criticized, Gould was offered a job at Princeton. The very next year, in a series of landmark papers, Gould began documenting neurogenesis in primates, thus confronting Rakic’s data directly
• Duman’s discovery of a link between trophic factors and antidepressant treatments still left the essential question unanswered: What was causing depressed brains to stop producing trophins?
• By 1999, even Rakic had admitted that neurogenesis is real. He published a paper in Proceedings of the National Academy of Sciences that reported seeing new neurons in the hippocampus of macaques, an old world primate.

• Robert Sapolsky, whose work on stress paved the way for much of Duman’s own research, is one of the most incisive skeptics. He argues that neurogenesis researchers have no plausible model for how decreased neurogenesis might cause the symptoms of depression. Why would having a handful fewer new cells in the hippocampus have such an effect? “The more expertise someone has about the hippocampus,” Sapolsky wrote in a review in Biological Psychiatry, “the less plausible they find this novel role.”

  
  
  

• Frisén has helped to change that. He has pursued the neurogenesis hypothesis into the realm of clinical medicine, and his rise has been astonishingly swift

• Neurogenesis is an optimistic idea. Though Gould’s lab has thoroughly demonstrated the long-term consequences of deprivation and stress, the brain, like skin, can heal itself, as Gould is now beginning to document, finding hopeful antidotes to neurogenesis-inhibiting injuries. “My hunch is that a lot of these abnormalities [caused by stress] can be fixed in adulthood,” she says. “I think that there’s a lot of evidence for the resiliency of the brain.”

  
  
  

• on 2006-12-18 Jaltcoh
  A mind-altering idea reveals how life affects the brain.
• on 2006-12-18 Jaltcoh
  A mind-altering idea reveals how life affects the brain.