The idea is that depression could be a feedback loop in which negative life events cause the brain to become chronically flooded by stress hormones like cortisol and epinephrine.
These are pro-inflammatory factors whose chronic presence promote run-away inflammatory responses which kill glial cells, decrease neuroplasticity, retard neurogenesis, and also contribute to a whole constellation of other health problems like obesity, diabetes, and heart disease.
What closes the feedback loop is that this inflammation-mediated form of brain damage, particularly in the hippocampus and amygdala, directly compromise a person's cognitive ability to deal with life stressors constructively. The ability to process emotion, fear, and memory degrade.
Speaking a bit poetically, you could say that a severely depressed brain is one that has rewired itself to be a stress-processing circuit.
SSRIs no doubt work for some people, and the modern thinking is that they might be promoting neurogenesis through upregulating BDNF and other growth factors; there are multiple lines of evidence, one fun one is the fact that the maturation time of new neurons roughly matches the time it takes for SSRIs to start affecting depression (3-6 weeks).
Exercise also works, seemingly about as well as SSRIs for many people with moderate depression (Googling will provide examples of studies from the last few couple decades to that affect). I haven't read much about this but I would imagine that the metabolic and cellular stresses of a bout of heavy exercise (in which millions of cells die) promotes the production of growth factors all over the body, including in the brain.
I think "negative life events" are more of a symptom than a cause. Temporary grief over loss or other genuinely bad things happening in life is normal in healthy people. What's so different about depression is that the patient seems to feel bad without a clear cause. You hear them going on about things that to a healthy person don't seem like such a big deal, or easy to fix, or so long ago a healthy person would have been over it by now. It's more a sign of the depressed brain trying to rationalize why it feels bad, and looking for outside causes to blame.
> Exercise also works, seemingly about as well as SSRIs for many people with moderate depression (Googling will provide examples of studies from the last few couple decades to that affect). I haven't read much about this but I would imagine that the metabolic and cellular stresses of a bout of heavy exercise (in which millions of cells die) promotes the production of growth factors all over the body, including in the brain.
Evidence is inconclusive for exercise; more research needed.
> When only high-quality trials were included, exercise had only a small effect on mood that was not statistically significant.
[...]
> Exercise is moderately more effective than no therapy for reducing symptoms of depression.
> Exercise is no more effective than antidepressants for reducing symptoms of depression, although this conclusion is based on a small number of studies.
> Exercise is no more effective than psychological therapies for reducing symptoms of depression, although this conclusion is based on small number of studies.
> The reviewers also note that when only high-quality studies were included, the difference between exercise and no therapy is less conclusive.
> Attendance rates for exercise treatments ranged from 50% to 100%.
> The evidence about whether exercise for depression improves quality of life is inconclusive.
So far a talking therapy, or a talking therapy combined with medication, are recommended for mild to moderate depression. That might change for some people with depression if we get better social interventions and lifestyle changes.
The idea is that depression could be a feedback loop in which negative life events cause the brain to become chronically flooded by stress hormones like cortisol and epinephrine.
These are pro-inflammatory factors whose chronic presence promote run-away inflammatory responses which kill glial cells, decrease neuroplasticity, retard neurogenesis, and also contribute to a whole constellation of other health problems like obesity, diabetes, and heart disease.
What closes the feedback loop is that this inflammation-mediated form of brain damage, particularly in the hippocampus and amygdala, directly compromise a person's cognitive ability to deal with life stressors constructively. The ability to process emotion, fear, and memory degrade.
Speaking a bit poetically, you could say that a severely depressed brain is one that has rewired itself to be a stress-processing circuit.
SSRIs no doubt work for some people, and the modern thinking is that they might be promoting neurogenesis through upregulating BDNF and other growth factors; there are multiple lines of evidence, one fun one is the fact that the maturation time of new neurons roughly matches the time it takes for SSRIs to start affecting depression (3-6 weeks).
Exercise also works, seemingly about as well as SSRIs for many people with moderate depression (Googling will provide examples of studies from the last few couple decades to that affect). I haven't read much about this but I would imagine that the metabolic and cellular stresses of a bout of heavy exercise (in which millions of cells die) promotes the production of growth factors all over the body, including in the brain.