Yes, Stress and Depression Make You Stupid.

From a SEED magazine article by Jonah Lehrer on Elizabeth Gould, the neuroscientist who overturned the long-held belief that adult brains don't make new nerve cells:

Eight years after Gould defied the entrenched dogma of her science and proved that the primate brain is always creating new neurons, she has gone on to demonstrate an even more startling fact: 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. [ ...]

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.” [ ... ]

Only a decade ago, the idea that the primate brain is constantly creating new neurons, and that these new neurons are not only functional but responsive to changes in the environment, was unimaginable. Indeed, the fact that neurogenesis did not exist was one of modern neuroscience's founding principles. [ ... ]

The genius of the scientific method, however, is that it accepts no permanent solution. Skepticism is its solvent, for every theory is imperfect. Scientific facts are meaningful precisely because they are ephemeral, because a new observation, a more honest observation, can always alter them. This is what happened to [the] theory of the fixed brain. [ ... ]

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.

(I can just feel my hippocampus shriveling. The hippos' habitat is shrinking. Tuition has become unaffordable.)

Baby rats only temporarily subjected to stress by being separated from their mothers grow up to have

a dramatic decrease in neurogenesis in their [ ... ] adult brains. The temporary trauma of childhood lingered on as a permanent reduction in the number of new cells in the hippocampus. The rat might have forgotten its pain, but its brain never did. [ ... ]

[I]f a pregnant rhesus monkey is forced to endure stressful conditions—like being startled by a blaring horn for 10 minutes a day—her children are born with reduced neurogenesis, even if they never actually experience stress once born. This pre-natal trauma, just like trauma endured in infancy, has life-long implications. The offspring of monkeys stressed during pregnancy have smaller hippocampi, suffer from elevated levels of glucocorticoids and display all the classical symptoms of anxiety. Being low in a dominance hierarchy also suppresses neurogenesis. So does living in a bare environment. [So does depression.] As a general rule of thumb, a rough life—especially a rough start to life—strongly correlates with lower levels of fresh cells. [ ... ]

From the perspective of the brain, stress and depression produced eerily similar symptoms. They shared a destructive anatomy.

Here's a fascinating cross-species fact about neurogenesis and what might be called creativity:

Fernando Nottebohm [ ... ] at Rockefeller [University ... ] 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.

Ronald Duman, professor of psychiatry and pharmacology at Yale, "realized that stress and depression didn’t simply kill cells, they might also prevent new cells from being born." He has discovered that antidepressants like Prozac don't merely work by boosting the available serotonin in the brain -- if they did, they'd lift depression overnight instead of having to be taken for weeks to feel an effect. Rather, at least in the rat brain, they seem to start a neurochemical cascade that triggers the release of trophic factors -- chemicals that stimulate the growth of new brain neurons. So-called electroshock therapy, used today as a treatment of last resort for intractable depression, appears to do the same thing.

[T]he two most effective treatments [Duman's lab] looked at—electroconvulsive therapy and fluoxetine, the chemical name for Prozac—increased neurogenesis in the hippocampus by 75% and 50%, respectively. [ ... ]

It is much more difficult to prove that increased neurogenesis causes the relief provided by antidepressants, and is not just another of the drug's many side-effects. To answer this question, Duman partnered with the lab of René Hen at Columbia.

The research team [ ... ] effectively erased neurogenesis with low doses of radiation. All other cellular processes remained intact. If the relief from depression was due to changes in serotonin, then halting neurogenesis with radiation should have had no effect.

But it did. Hen and Duman’s data was unambiguous. If there is no increase in neurogenesis, then antidepressants don’t work in rodents. They stay “depressed.”

This work is still scientifically controversial, and it has its skeptics, but if it's borne out by further research -- if a new generation of antidepressants in development, deliberately designed to stimulate neurogenesis (in the case of Prozac it was serendipity), proves effective -- it will suggest that

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.

Frisén has founded a pharmaceutical start-up, NeuroNova, that seeks drugs to treat ailments like Parkinson's Disease ("caused by the death of dopamine-producing neurons") by stimulating neurogenesis.

The results so far have exceeded everyone’s expectations. In November 2005, NeuroNova announced that one of their leading drug candidates—clandestinely called sNN0031—restored normal bodily movement in rodent models of Parkinson’s. Rats that were barely able to walk had their symptoms erased after only five weeks of treatment. Furthermore, initial results suggest that the drug worked by rapidly increasing neurogenesis, thus restoring normal dopamine signaling in the rat brain. “The results really are spectacular,” Frisén says.

The next step is to begin testing in primate models of Parkinson’s, beginning early this year. If the drug doesn’t produce toxic side effects—and that’s unlikely, since it is already approved as a human treatment for an unrelated condition—human clinical trials are expected to begin shortly thereafter.

But it isn't just drugs that can reverse the long-term brain-stunting effects of deprivation and stress. An enriched and stimulating environment can coax the brain to begin to flourish and recreate itself again. "On a cellular level, the scars of stress can literally be healed by learning new things."

(T.H. White, in The Once and Future King, wrote, "The best thing for being sad is to learn something. That is the only thing that never fails.")

This research is done, of course, by treating lab animals -- from rats to monkeys -- in contrasting ways, then killing them and microscopically examining their brain neuron density and connections.

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.”

Gould has also become concerned about the details of experimental design. She now stresses the importance, for both rodents and primates, of living in a naturalistic setting. An artificial cage creates artificial data.

Animal lover though I am, I think this knowledge is worth the price -- even though any aborigine could probably tell you essentially the same thing. It makes you wonder about the brain-impoverishing effects on humans of being removed from the "enriched environment" of nature. Exactly what Richard Louv, author of Last Child in the Woods, is talking about.

The Seed article ends with a caution that the field of neurogenesis is new, uncertain, and modest in its claims, and that all of the above is so much leaping to unwarranted conclusions. It's thought-provoking stuff, though. I've probably sparked a neuron or two, and cheered myself up, by blogging it. (And oh, the implications for blogging!!)

Just in time for more stress. Off to the airport!

Comments

[realpc]

It is interesting, because the assumption had always been that we just keep losing brain cells and therefore must lose intelligence as we get older. Also, it was believed that intelligence measured during childhood cannot increase very much.

When a child gets labeled as not very smart, he loses motivation for intellectual learning and will probably stay that way for life. It's nice to know that cycle can be escaped, and anyone can grow their brains and become smarter.

The implications for aging are positive, because it means declines in intelligence probably result mostly from physical health problems, many of them caused by lifestyle. I think if we can stay somewhat healthy and continue learning, we won't lose intelligence and might even become smarter.

In my own experience, my intelligence was always related to motivation and curiosity. If I really wanted to learn something, I always did.

One problem of living in a meritocracy is that being born with intelligence, or talent, has replaced being born an aristocrat. We think some have it and others don't, and everyone must accept their rank. It starts in grade school.

I read something about this recently at another web site. It described a guy who seemed to be an intellectual loser in his 20's, until he finally became interested in something and became a highly successful scientist.

I would like to know how often this happens, and I think the new discoveries will motivate people to continue learning. I experienced this a lot in my own life, so I was always skeptical of the fixed-brain theory.

As for the rich environment of nature -- I don't know, humans are much more flexible than animals. We can experience a rich environment from staying inside and reading, or from technology.

[Sissy Willis]

I leap to unwarranted conclusions, therefore I am.

A wonderful post . . . I have, indeed, learned something, and my brain cells are jumping for joy.

Blogging = Prozac on steroids?

[Mark Ribado]

HI, Nice post. I just happen to stumble through. I cannot stress more the impact our environment has. I have two young children and witness this daily. This does however concern me. When it comes to the Television I dont know what to think. I already own numerous internet filtering programs, I just dont want my children to to be exposed to certain things. I think that the mainstream media is not helping the situation. What do you think? Post something, I'm sure your fans would like to know your thoughts.

[Jille]

This is a terrific piece. Thanks for bringing this study to my attention.

[Charlie (Colorado)]

Funny, it seems to work both wayas too --- stupidity makes me stressed and depressed.

[Jeff]

Confidence can make even the dumbest people seem intelligent. I currently struggle with a severe depression. When I am down I feel stupid and therefore i act stupid. On the rare occasion that i feel happy, I show intelligence. Depression makes your mind wander, You overanalyze everything in your life. In actuality you are not stupid, its just your mind is so cluttered with depressive thoughts that its hard to sound articulate when you speak, because your not mind is not focused. If you have nothing to worry about then these things come easier.

[Lauren]

Thank you for this info. It makes me feel hopeful that out of the 24 jobs I have had in my life there may be a chance I am not totally incompetent. I go to work with a smile and good intentions but I am so absent minded that I constantly make carelss mistakes that make me look stupid and I just cant keep saying I'm sorry. I had to take the elevator back to my floor three times after work today because I couldnt remember for sure if I locked the office door just moments before.

Defeated

[amba]

What you are describing may be obsessive-compulsive disorder (OCD). It isn't psychological, it's a neurological phenomenon, and it is treatable. Please check it out. I strongly recommend this book, for one.

[Brendan]

To "amba":
Where is the scientific proof that OCD (or any other "mental illness" is neurological? THERE IS NONE! That is just the currently-fashionable, personal responsibility-ducking politically correct explanation for what is actually a character issue (namely, mental immaturity if not a just plain lack of intelligence.)