The idea that some people see the glass as half empty while others see it as half full goes back a long time. You have probably noticed it in your own social circle: Some lucky individuals seem perpetually upbeat, while others take any slight disappointment as proof that they are in a downward spiral.

It’s not been totally clear why this is the case, but it seems almost hardwired into us, since even though it's clear that life events can change a person’s outlook considerably, everyone experiences difficult life events, but not everyone responds to them so deeply.

Now researchers, using mice as their subjects, have discovered an area of the brain that may be responsible for how affected we are by negative events. And, the thinking goes, if we can learn how to “dim” this area of the brain — dubbed the “disappointment pathway” — then we may be able to dial down depression as well.

We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experiences.

The main finding of the study was that the area of the brain called the lateral habenula (LHb) secretes both the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA. Excitatory neurotransmitters signal other brain cells to increase their activity, while inhibitory neurotransmitters suppress activity in other brain cells.

Usually neurons secrete just one, not both, chemical messengers, so the fact that this area secretes both is intriguing.

“Our study is one of the first to rigorously document that inhibition can co-exist with excitation in a brain pathway,” said lead author Steven Shabe. “In our case, that pathway is believed to signal disappointment.”

Previous work had shown that monkeys who are expecting a treat but don’t get one have increased activity in the LHb, which suggests that it may in fact be involved in the subjective feeling of disappointment.

The current study also found that in the animals who showed symptoms equivalent to depression in people, neurons in the LHb secreted more GABA and less glutamate. But when they were given serotonin reuptake inhibitors, SSRI antidepressants, the levels of the two neurotransmitters evened back out, hinting that one way antidepressants exert their effects is by affecting this disappointment area of the brain.

“Our study suggests that one of the ways in which serotonin alleviates depression is by rebalancing the brain's processing of negative life events vis-à-vis the balance of glutamate and GABA in the habenula,” Shabel said. “We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experiences.”

There’s still a lot about antidepressants that researchers don’t know — but this study lends some clues as to how they might work. They may act like a dimmer switch for the “disappointment pathway” in the brain. It’s also possible that other methods — like talk therapy, exercise, and yoga or meditation — may also affect the brain in similar ways.

It’s one thing to be a little pessimistic at times. But if you’re experiencing more severe depression, talk to your doctor about different methods to treat it. Science may not always understand why a treatment works — but it does tell us that certain treatments can work quite well, provided you find the right one.

The study was carried out by a team at UC San Diego and published in the journal Science.