Rumination and the life I “should” have had

I have been thinking lately about how the brain creates continuous narratives about our past and future, stories about what should have happened and what is supposed to happen next. These narratives set expectations, but in depression, this tendency often turns into rumination. The APA Monitor describes rumination as part of a self-reinforcing cycle where negative thinking deepens a low mood, which in turn fuels more negative thinking (https://www.apa.org/monitor/nov05/cycle).

A depressed brain can easily fixate on how life “should” have gone, how it did not, and why the current outcomes now seem bad. Instead of moving toward problem-solving, the mind circles the same themes over and over. What interests me even more, though, is not just the repetition of these thoughts, but the underlying assumption behind them.

The content of those thoughts does not always make logical sense. Since I do not believe in higher powers or destinies, I don’t believe any human is born to be anything specific; people just happen to be born. The idea that my life “should” have followed a particular path isn’t grounded in any law of physics or biology. It is simply the brain constructing a narrative and then treating that narrative as if it were objective truth.

Psychologists also point out that rumination is less about the negative content and more about a repetitive style of thinking. It is the act of recycling thoughts without moving toward action. It feels like analysis, but it isn’t actually solving anything.

https://www.psychologytoday.com/ca/blog/triggered/201912/when-depression-meets-ocd-understanding-rumination

I have definitely been prone to forming these rigid narratives about how things “should” be for me. Until my early twenties, I carried a constant narrative that I was an “upcoming writer,” even though I only really wrote in a diary, some LiveJournal posts, and a few short stories. While I wasn’t depressed at the time, my brain was already getting stuck in specific stories. During much of my undergrad, for instance, I told myself that finance courses were boring and “not for me.” I convinced myself I wasn’t like the students destined for corporate jobs; my passion was writing, and I just needed to get my degree over with so I could finally focus on it.

After undergrad, when I had to get a job to pay rent and still hadn’t started a book, my narrative simply shifted. I decided I would be a professor because 9-to-5 jobs weren’t for me. I told myself I was smarter than that and was going to do something more impactful, like research, even though I had always been an average student. Consequently, when I couldn’t complete my PhD because I didn’t actually have any thesis ideas, I started to feel like I was disappearing.

I have written before about having autoimmune encephalitis in my mid-twenties, which definitely contributed to my depression. However, I also think a lack of cognitive behavioral therapy skills and the persistence of these rigid narratives played a role in that feeling of disappearing.

The CBT advice for dealing with this is often quite simple: interrupt the loop. The American Psychiatric Association suggests deliberately breaking the cycle through physical activity or by breaking problems into small, actionable steps. The goal is to turn abstract thinking into concrete movement (https://www.psychiatry.org/news-room/apa-blogs/rumination-a-cycle-of-negative-thinking).

I’ve noticed that these narratives create a direct conflict in my brain. One part of me insists that I failed because I didn’t become a professor, writer, economist, or doctor. I just have a regular 9-to-5 job. But at the same time, I realize I don’t actually want to work long hours or deal with high-level work stress. I enjoy hiking or cross-country skiing during my lunch breaks. I like swimming in an outdoor pool at noon on a weekday. I actually prefer lower responsibility and more free time.

There is a clear tension here: one part of my brain insists I should have been something extraordinary, while another part actually prefers a calm and ordinary life. Perhaps the skill isn’t to eliminate these narratives entirely, but to simply notice that they are stories, not laws of nature.

Did your psychiatrist talk to you about CYP2D6, SLC6A4, and HTR2A genes and SSRI response?

I think this is a very important topic. There is now sufficient evidence to indicate that people with specific variations of genes CYP2D6, SLC6A4, and HTR2A, are unlikely to respond to SSRIs. The evidence indicates that especially Caucasian females are unlikely to respond to SSRIs, if they have the genes SLC6A4 S/S and HTR2A G/G. Evidence also shows that they may not respond to SNRIs as well.

If you are in this population, I wonder if your psychiatrist spoke to you about this. I think it’s a pretty big deal, given the sufficient evidence for Caucasians.
I am an Eastern European female, and I had no response at all to any SSRIs or SNRIs, or any medication in general so far. I had trials of mirtazapine, sertraline, abilify, latuda, risperidone, olanzapine, fluoxetine, pristiq, cymbalta, and seroquel. I was then referred to a more specialized psychiatric hospital, and they performed genetic testing for me. The results indicated that I have SLC6A4 S/S and HTR2A G/G genes. The medical records state the following:

SLC6A4 S/S
Homozygous for the short promoter polymorphism of the serotonin transporter gene. The short promoter allele is reported to decrease expression of the serotonin transporter compared to the homozygous long promoter allele. The patient may experience a delayed response with selective serotonin reuptake inhibitors, or may benefit from non-selective antidepressants.

HTR2A G/G
Homozygous variant for the G allele for the serotonin receptor type 2a. Two copies of the G allele. This genotype has been associated with an increased risk of adverse drug reactions with certain selective serotonin reuptake inhibitors.

CYP2D6 intermediate metabolizer – Higher plasma concentrations may increase the probability of side effects. Consider a lower starting dose and slower titration schedule as compared with normal metabolizers.

I think given that I have not responded to any of the medications (each one was tried for over 8 weeks), and these test results, it’s pretty clear that I am very unlikely to respond to any other SSRIs or SNRIs. I had a very good neuropsychiatrist at the psychiatric hospital, but unfortunately I was transferred to another hospital due to pregnancy. Now I have a psychiatrist who is a resident, so she does not have a lot of experience. I was prescribed lamotrigine and fluoxetine. I think the lamotrigine makes sense, given that I have no tried it, but she only gave me 25mg per day. I don’t think the fluoxetine makes sense, because it’s an SSRI, and I have already tried it. I also stopped sleeping starting the first day I began to take it. I have been sleeping only 3-4 hours a day since I started it 8 days ago.

I wonder if anyone had a good doctor who discussed with them genetic testing and what were their suggestions? What are the options if there is no response to SSRIs and SNRIs? I don’t think my resident psychiatrist has enough experience in this.