The serotonin theory of depression: a systematic umbrella review of the evidence
I&#x27;ve experienced a lot of depression in my life and it feels fairly obvious that the chemical imbalance state -- the feeling of extreme torpor, lack of motivation to do things, negativity about future prospects, and inability to enjoy anything -- is well downstream of the root cause, which is a sort of &quot;software problem&quot; that looks like this:<p>The problem is that there is a mis-alignment between the reality of daily life and the software my brain has constructed for handling and processing daily life. The software doesn&#x27;t give good results on the inputs: for instance, not having a good script for what to do with time to feel happy or like myself, or not knowing how to navigate social situations to get positive and fulfilling results. The result is the brain gives up on the software and stops trying because it&#x27;s become aware it&#x27;s not working but doesn&#x27;t have any better ideas.<p>If I was programming my brain, a better strategy would obviously be to switch to &quot;explore&quot; mode and start rapidly iterating on the software to try to find something that works better. But evidently the brain doesn&#x27;t work that way, and the negative feedback from real life causes it to slip into depression and torpor.<p>So there&#x27;s a chemical imbalance, yeah, but it&#x27;s not the root cause. If a &quot;chemical disposition to depression&quot; is anything, it&#x27;s this tendency to give up on the software instead of iterating on it.<p>(IRL, &quot;iterating on the software&quot; looks like a person making big changes in their life: quitting jobs, moving, leaving relationships, picking up new hobbies.. you know, all of the stuff people advise you to do to get out of a funk. 
&quot;Changing variables until something works&quot;.)<p>SSRIs, at least the ones I&#x27;ve taken, seem to work by reducing the severity of the (bad results from software) -&gt; (downregulate energy levels) step; in particular, the reduce the amount of fixation my brain gives on the bad results and makes me not worry so much about them, which -- presumably -- reduces the amount of the downregulation that results, which prevents slipping into the extreme-depressive state where you have no willpower to try anything new that might help.<p>In particular I observe that my natural tendency is for negative social interactions to trigger a negative feedback loop of self-doubt and frustration that spirals out of control, and Lexapro seems to reduce the coefficient on the feedback loop so that it dissipates instead of amplifies.<p>(I&#x27;m not all that confident in this model but it&#x27;s my best guess so far. I&#x27;ll also add that a lot of my depressive states seem to have social anxiety as the main trigger, so it might be that this is phenomenologically quite different from sorts of depression that are, I guess, &quot;intrinsic&quot;, rather than caused by something else.)