MEDICINE : depression and prescribed anti-depressants

SYSTEMATIC REVIEW (OPEN Access)

The serotonin theory of depression: a systematic umbrella | review of the evidence
Joanna Moncrieff 1,2 ✉, Ruth E. Cooper3 , Tom Stockmann4 , Simone Amendola 5 , Michael P. Hengartner6 and Mark A. Horowitz 1,2
© The Author(s) 2022

https://www.nature.com/articles/s41380-022-01661-0.pdf
(abstract) https://pubmed.ncbi.nlm.nih.gov/35854107/

Nature Journals
Molecular Psychiatry July 2022

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ETA: also by Dr. Joanna Moncrieff, with Dr. David Cohen

Do Antidepressants Cure or Create Abnormal
Brain States? | Joanna Moncrieff*
, David Cohen (PLoS Medicine)

DOI: 10.1371/journal.pmed.0030240

Copyright: © 2006 Moncrieff and Cohen.

This is an open-access article distributed under the terms
of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.

Abbreviations:
RCT, randomised controlled trial;
SSRI, selective serotonin reuptake inhibitor;
TCA, tricyclic antidepressant

Joanna Moncrieff is a senior lecturer in Psychiatry,
University College London, London, United Kingdom.
David Cohen is a professor at the School of Social
Work, College of Health and Urban Affairs, Florida
International University, Miami, Florida, United States
of America.

* To whom correspondence should be addressed.
E-mail: j.moncrieff@ucl.ac.uk

Mechanism of action is a work in progress. Currently unknown. Would be nice to know.

As a person who has been on SSRIs for almost 30 years I found this article incredibly interesting. Maybe I'll broach discontinuing my med with my doctor.

>3 gypsysmom:
Wendy,
despite our having, I suspect, many differences of opinion in some respects, I wish you all good luck in discussing the matter of SSRIs with your specialist or general practice physician and all my best wishes in your battle with long-term depression.

You may live just far enough East in Canada to have a working knowledge of French--for reading purposes. If so, then I also recommend for you this work which truly revolutionized my science views--particularly in microbiology, cellular biology and in another essential area of study, statistics:

Pierre Sonigo (INSERM ),

https://www.worldcat.org/title/ni-dieu-ni-gene-pour-une-autre-theorie-de-lheredi...

https://www.librarything.com/work/970697/book/90755123
Ni Dieu ni gène: Pour une autre théorie de l'hérédité
("Neither God Nor Gene: For Another Theory of Heredity";
by Jean-Jacques Kupiec & Pierre Sonigo; 2003, Éditions du Seuil| Series: Points., Sciences (No.) S153)

Dr. Sonigo, director of the laboratory "Génétique des virus" was part of the French team of researchers at the Institute Pasteur which sequenced the DNA of the virus responsible for AIDS in 1985.
(Some of the following details borrowed from Wikipedia pages)

No less brilliant in molecular biology, his co-author, Jean-Jacques Kupiec, Ph.D., ('Université Paris-7 at Jussieu (now the Université PARIS-Diderot)), has been a researcher in these same areas at the Virology laboratories at l'INSERM* in the 1980s, and was also part of the team which first sequenced the AIDS virus. From 1990, he devoted himself to the study of the HIV protéase and, from 2004, has worked exclusively on the development of a new theory of embryogenesis. His breakthrough theory is "ontophylogenesis" which he explains in his major work, L'ontophylogenèse : évolution des espèces et développement de l'individu ("Ontophylogenesis: Evolution of species and development of the individual") |
Institut national de la recherche agronomique (France); Publisher: Versailles : Éditions Quæ, ©2012. and in his L'Origine des individus, Paris, Éditions Fayard, coll. « Le Temps des Sciences », 2008. (If you don't read French, this same was published in an English translation, The Origin of Individuals, World Scientific Publishers, Singapore, 2009).

All of these works are world-changing in their brilliance and I've read and have had multiple copies of them in my personal library. In importance, I rank the work of Kupiec and Sonigo as equal to that of Charles Darwin's On the Origin of Species -- that is, the most important medico-scientific work since Darwin's time.

You can help spread the word.

And, as if the Serotonin scandal weren't enough, only recently, there's been this reported in the press:

" Seminal Alzheimer's study claiming memory-robbing disease was caused by build-up of protein in brain may have been MANIPULATED, damning investigation claims Images used to prove a protein is behind Alzheimer's may have been tampered | (London) Daily Mail | By Joe Davies, Health Reporter For Mailonline Published: 10:45, 22 July 2022 | Updated: 11:20, 22 July 2022

See also this thread (https://www.scienceforums.net/topic/68764-on-ontophylogenesis-or-cellular-darwinism/#comments) from a decade ago. Think "Culture wars" are brutal? Those have nothing on science-theory wars. ;^ (

More recent studies:

Article
Open Access
Published: 25 July 2022
Translational Psychiatry volume 12, Article number: 294 (2022)

Title: The interaction of early life factors and depression-associated loci affecting the age at onset of the depression Authors: Yujing Chen, Chuyu Pan, Shiqiang Cheng, Chun’e Li, Huijie Zhang, Zhen Zhang, Jingxi Zhang, Yao Yao, Peilin Meng, Xuena Yang, Li Liu, Bolun Cheng, Yumeng Jia, Yan Wen & Feng Zhang | DOI:

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("fn n" = References' footnote numbers)
(Excerpt)


"INTRODUCTION

"Depression is a widespread chronic medical illness often presenting with physical symptoms (fn1). Over the past several decades, the amount of people with depression have increased leading to a growing concern in mental health research around the world (fn2).

"According to the report of WHO, the global population suffering from depression was estimated to be 322 million, accounting for 4.4% of the global population that resulting in a surge in suicide rates as well as a huge social and economic burden (fn3).

"Depression is a highly heterogeneous syndrome (fn4). Various factors including different age at onset of the depressive episode, varying symptom profiles, different levels of symptom severity, and duration may contribute to clinical heterogeneity (fn5). The age at onset of depression is the main reason for the clinical heterogeneity of depression (fn6). Children having parents with early onset major depressive disorder (MDD) (30) MDD is estimated to be much lower (h 2 = 0.10) (fn8). Early-onset depression and late onset depression may have different pathogenesis(fn9). It has long been suggested that early onset MDD is associated with increased risk of the disorder in first degree relatives, while late onset MDD was associated with increased familial risk of vascular disease (fn6, fn10). With increasing age, the course of depression became worsen(ed). In a recent large cohort study of adults aged 18–88 years, people aged 70 and above experienced greater symptom severity compared with younger adults (fn11).

"Therefore, the age at onset of the depression is important for the development of depression."

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References (relevant to this excerpt):

1. Rakel RE. Depression. Prim Care. 1999;26:211–24.

2. Aaronson ST, Sears P, Ruvuna F, Bunker M, Conway CR, Dougherty DD. et al. A
5-year observational study of patients with treatment-resistant depression trea-
ted with vagus nerve stimulation or treatment as usual: Comparison of response,
remission, and suicidality. Am J Psychiatry. 2017;174:640–8.

3. Friedrich MJ. Depression is the leading cause of disability around the world.
JAMA. 2017;317:1517.

4. Lynch CJ, Gunning FM, Liston C. Causes and consequences of diagnostic het-
erogeneity in depression: Paths to discovering novel biological depression sub-
types. Biol Psychiatry. 2020;88:83–94.

5. Sharma V, Doobay M, Baczynski C. Bipolar postpartum depression: An update and
recommendations. J Affect Disord. 2017;219:105–11.

6. Power RA, Keers R, Ng MY, Butler AW, Uher R, Cohen-Woods S, et al. Dissecting
the genetic heterogeneity of depression through age at onset. Am J Med Genet B
Neuropsychiatr Genet. 2012;159B:859–68.

7. Wickramaratne PJ, Weissman MM. Onset of psychopathology in offspring by
developmental phase and parental depression. J Am Acad Child Adolesc Psy-
chiatry. 1998;37:933–42.

8. Lyons MJ, Eisen SA, Goldberg J, True W, Lin N, Meyer JM, et al. A registry-based
twin study of depression in men. Arch Gen Psychiatry. 1998;55:468–72.

9. Cheng YC, Liu SI, Chen CH, Liu HC, Lu ML, Chang CJ, et al. Comparison of
cognitive function between early- and late-onset late-life depression in remission.
Psychiatry Res. 2020;290:113051.

10. Kendler KS, Fiske A, Gardner CO, Gatz M. Delineation of two genetic pathways to
major depression. Biol Psychiatry. 2009;65:808–11.

11. Wilkinson P, Ruane C, Tempest K. Depression in older adults. BMJ.
2018;363:k4922.

Other studies :
Effects of early life stress on depression, cognitive performance and brain morphology |
Published online by Cambridge University Press: 29 September 2016
Authors: A. Saleh, G. G. Potter, D. R. McQuoid, B. Boyd, R. Turner,J. R. MacFall and W. D. Taylor

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Early Life Influences on Life-long Patterns of Behavior and Health | Bruce S. McEwan, Laboratory of Neuroendocrinology, Rockefeller University, New York, N.Y. | (Journal) Mental Retardation and Developmental Disabilities Research Reviews, 9, 149-154, (2003).

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The role of specific early trauma in adult depression: A meta-analysis of published literature. Childhood trauma and adult depression | Published online by Cambridge University Press: 13 June 2015 | Authors: L. Mandelli, C. Petrelli and A. Serretti

NOTE : It may be worth pointing out that I did not merely stumble upon these studies. Rather, I searched on the key-terms "depression" and "early childhood" and "trauma" because I suspected that they were related in important ways which may be the topic of research.

>5 proximity1: “ NOTE : It may be worth pointing out that I did not merely stumble upon these studies. Rather, I searched on the key-terms "depression" and "early childhood" and "trauma" because I suspected that they were related in important ways which may be the topic of research.”

War torn countries have higher rates of depression perhaps?

>6 DugsBooks:

That's my working assumption. Lately I've been dwelling on the widespread trauma which must be the lot of the generation of psychically damaged young children who've been subject to the trauma of the war and destruction in Ukraine. But, of course, this same goes for all very young children in all war zones--in all times. This is a disastrous "universal" in part because, unlike in centuries past, modern war often has no battle "fronts", no rear zones of relative quiet, no civilian populations spared the horrors of combat and ruinous destruction.

Victor Davis Hanson's work, tells of how this all changed--for Western culture--with the Peloponnesian wars between Athens and Sparta and their allies. (https://en.wikipedia.org/wiki/History_of_the_Peloponnesian_War)

A War Like No Other
https://www.librarything.com/work/12195
Victor Davis Hanson