In many patients, depression is associated with memory dysfunction. Now the results of a large study involving brain scans show that patients with moderate to severe depression have 7-10 per cent fewer serotonin 4 receptors in the brain than healthy test subjects.

The researchers from the University of Copenhagen, Psychiatry in the Capital Region and Rigshospitalet performed PET scans of 90 patients with depression who still had not received treatment and just as many healthy test subject of the same age. A PET scan will reveal the amount of serotonin 4 receptors in the brain.

“You cannot tell from a scan whether a person is depressed or not. But we could tell that there was a difference between the patients and the test subjects. The former had fewer serotonin 4 receptors,” says Clinical Professor Gitte Moos Knudsen from the Department of Clinical Medicine and the Neurobiological Research Unit at Rigshospitalet.

Largest PET brain scan study of its kind Previous studies have shown that the serotonin 4 receptor affects the risk of depression, while others have shown that it is associated with human memory. The new results, which have just been published in the scientific journal JAMA Psychiatry, are based on the largest PET brain scan study ever to have been conducted on patients suffering from depression. The aim of the study was to describe the connection between depression, memory dysfunction and low receptor levels.

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2801424

For what it’s worth, I was put on Remeron for general anxiety. Apparently it’s a bit different from regular antidepressants/anti anxiety and rarely has side effects.

My memory is 50x what it was before. I can glance at a piece of junk mail that mentions a class action lawsuit hearing that’s on October 5th and to call or email before August 8th to be considered part of the suit.

It’s pretty bizarre.

> This study may pave way for new drugs.

It would be nicer if it could pave the way to hindering depression, but I guess we all have different incentives..

As someone who suffered from clinical depression for ~4 years, my brain does not function like it did before, particularly regarding memory. It feels fundamentally different.

So does SSRI treatment reverse memory-loss to any degree? I know from experience that memory loss can make it difficult to engage socially which is important for beating the depression

This is completely true, based on personal experience.

> there was a correlation between cerebral 5-HT4 receptor binding and verbal memory (r = 0.29; P = .02)

a correlation of r=0.29 is absolutely abysmal, look at the graphs they provided and tell me with a straight face these "correlations" mean anything

I don't understand the value of this research. Depression has been known to correlate with memory dysfunction and decreased hippocampal volume. 5-HT4 (serotonin 4) receptors have been known to be involved with memory, and the structural plasticity effects within the hippocampus.

However, compared to other serotonin receptors, the function of 5-HT4 throughout the brain and periphery is diverse and complex — which makes sense when considering how relatively large / complicated the gene encoding 5-HT4 is, and how little is known about the regulation of its transcription.

There is strong evidence regarding the involvement of 5-HT4 in depression, but imaging that quantifies global reductions is completely insufficient. Humans show different responses in 5-HT4R expression in different brain regions. SSRIs have been shown to decrease global 5-HT4 binding. Depressed suicide victims show increased 5-HT4 receptor binding in the caudate nucleus and frontal cortex.

This study has zero value in paving the way for new drugs.

That reminds me of a study I read where depression can lead to memory dysfunction. Memory dysfunction was in a story I read about depression.

But, yeah, all joking aside, I super relate to this.

I suspect this is just a correlation thing rather than causative. For your brain to function properly you need to have a good diet, sleep and exercise. If you aren't doing those then your brain isn't going to work properly showing up as things like memory dysfunction and depression.

We have studies that show the causal effect of exercise and have a ideas on the mechanisms why

>Aerobic exercises, including jogging, swimming, cycling, walking, gardening, and dancing, have been proved to reduce anxiety and depression.3 These improvements in mood are proposed to be caused by exercise-induced increase in blood circulation to the brain and by an influence on the hypothalamic-pituitary-adrenal (HPA) axis and, thus, on the physiologic reactivity to stress.3 This physiologic influence is probably mediated by the communication of the HPA axis with several regions of the brain, including the limbic system, which controls motivation and mood; the amygdala, which generates fear in response to stress; and the hippocampus, which plays an important part in memory formation as well as in mood and motivation.
>
>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1470658/#i1523-5998-8-2-106-b3

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We have studies showing that exercise is just as effective as medicine in treating depression

>Four trials (n = 300) compared exercise with pharmacological treatment and found no significant difference (SMD -0.11, -0.34, 0.12). From https://pubmed.ncbi.nlm.nih.gov/24026850/

Exercise has massive effects on mitochondria, which might be partly a mechanism in relation to depression. >Mitochondria Linked to Major Depression in Older Adults https://today.uconn.edu/2023/02/mitochondria-linked-to-major-depression-in-older-adults/#>

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Depression is linked to lower brain volume

>Conclusion: Our results suggest that lower CV fitness and exaggerated exercise BP and HR responses in middle-aged adults are associated with smaller brain volume nearly 2 decades later. Promotion of midlife CV fitness may be an important step towards ensuring healthy brain aging.
>
>https://n.neurology.org/content/86/14/1313.short?rss=1

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>We found that longitudinal measures of cortical atrophy were widely correlated with sleep quality. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162301/

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>A better diet quality is associated with larger brain tissue volumes.
>
>https://pubmed.ncbi.nlm.nih.gov/29769374/

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>This study shows that a more severe and chronic lifetime disease course in MDD is associated with reduced volume in brain regions relevant for executive and cognitive functions and emotion regulation in a large sample of patients representing the broad heterogeneity of MDD disease course. https://onlinelibrary.wiley.com/doi/10.1002/da.23260>

Sleep is really important, if you aren't sleeping properly you have have a tenfold higher risk of depression,

>People with insomnia , for example, may have a tenfold higher risk of developing depression From https://www.hopkinsmedicine.org/health/wellness-and-prevention/depression-and-sleep-understanding-the-connection

Then there is diet

>The diet may have a significant effect on preventing and treating depression for the individual. A diet that protects and promotes depression should consist of vegetables, fruits, fibre, fish, whole grains, legumes and less added sugar, and processed foods. In the public health nurse’s preventative and health-promoting work, support and assistance with changing people’s dietary habits may be effective in promoting depression. From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084175/

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>Current evidence supports the finding that omega-3 PUFAs with EPA ≥ 60% at a dosage of ≤1 g/d would have beneficial effects on depression Https://www.nature.com/articles/s41398-019-0515-5

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I wonder if psychedelic drugs can improve memory function. LSD, psilocybin, and MDMA are serotonin receptor agonists.

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The environment we live in is changing our biology