How do ADs really work?

[lebonvin]

This is a question for Panic down under.

You wrote about ADs making new brain cells but I can't find the place.

I always thought it was because of a chemical imbalance that you'd get depression but apparently not.

Could you explain in a kinda easy and not too scientific way for dummies like me what caused depression and anxiety and why ADs work for some/most people?

Thanks

[lebonvin]

Hey panic

Can yous also explain meaning of reuptake inhibitor? I always thought serotonin and noradrenaline was our friends but those words point to the opposite

[panic_down_under]

You wrote about ADs making new brain cells but I can't find the place.

I always thought it was because of a chemical imbalance that you'd get depression but apparently not.

There is no 'chemical imbalance.' That hypothesis was disproven almost as soon as it was conceived, but it has become a popular analogy promoted by doctors and the drug companies as a simple explanation which most people can understand whereas the true causes are complicated. See my:
Serotonin - The 'chemical imbalance' myth (http://www.nomorepanic.co.uk/showthread.php?t=193671)

Anxiety and depression are not illnesses in their own right. There is no such thing as a "mental" illness. The mind is merely an emergent property of the brain. It has no separate existence so cannot become ill. Anxiety and depression are instead the symptoms of a physical brain disorder, the loss of brain cells (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/) (atrophy) of the two hippocampal areas of the brain caused by high brain stress hormone levels, mostly of cortisol, killing hippocampal cells and inhibiting the growth of new ones. These hippocampal regions are about 20% smaller than normal in those with anxiety and/or depression. See also:


Depression and the Birth and Death of Brain Cells (PDF (https://www.americanscientist.org/sites/americanscientist.org/files/20057610584_306.pdf)).


What happens inside people’s brains when they’re depressed? (https://psycheducation.org/depression-is-not-a-moral-weakness/chapter-6-what-happens-inside-peoples-brains-when-theyre-depressed/)

In several respects this should be regarded as an auto immune disorder. Support for this is provided by immune system boosting drugs such as interferon used to treat some cancers and viral infections which often trigger anxiety and especially depression. So much so that SSRIs are also now routinely prescribed to patients about to be treated with them. Immune system proteins can also reduce the effectiveness (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337012/) of antidepressants. For more on mood disorders and the immune system see:


Interferon-Related Depression: A Primer on Mechanisms, Treatment, and Prevention of a Common Clinical Problem (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050402/)


Inflammation and depression: a causal or coincidental link to the pathophysiology? (https://www.cambridge.org/core/journals/acta-neuropsychiatrica/article/inflammation-and-depression-a-causal-or-coincidental-link-to-the-pathophysiology/5C2C06EEA9F9F6EBFCA5522685F24BC1/core-reader)

Antidepressants seem to have two modes of action, they stimulate neurogenesis (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/) and most are pretty good anti inflammatories (http://www.ijps.ir/article_2042.html). Therapy seems to work by the same neurogenesis mechanism (http://tiny.cc/h0xzaz) as do Omega-3/fish oil (http://www.ncbi.nlm.nih.gov/pubmed/23746276) supplements and exercise (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413959/) to a lesser extent although they may be all that's needed for mild anxiety and/or depression.


Can yous also explain meaning of reuptake inhibitor? I always thought serotonin and noradrenaline was our friends but those words point to the opposite

When a neuron depolarizes ('fires') it releases a neurotransmitter across the synaptic gap to the next neuron. To conserve energy after a few microseconds the neurotransmitters (NTs) are pulled back out of the gap by transporter proteins, fairly simple protein molecules studded through the synapse membrane which latch onto a NT molecule and then twist to carry, i.e. reuptake, it back into the cell for reuse. Serotonergic and noradrenergic/norepinephrinergic antidepressants inhibit this by blocking their respective transporter molecules (SERT, NET) which delays the reuptake of the NT. That is they keep the NT within the synaptic gap for longer increasing its effectiveness. At least 80% of the NT transporters need to be blocked to achieve‪ an effective therapeutic response with most ADs (https://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitor#SERT_occupancy) reaching that target at the recommended minimum dose (citalopram may be the exception).

[lebonvin]

OK comprendo. Had to read over a few times but all makes sense. Some of your links are kinda long but intend to read at my own pace.
I feel this is stuff that everyone should know.