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Serotonin and depression—an alternative interpretation of the data in Moncrieff et al.

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  1. Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2022. Online ahead of press.

  2. Depue RA, Spoont MR. Conceptualizing a serotonin trait. A behavioral dimension of constraint. Ann NY Acad Sci. 1986;487:47–62.

    Article  CAS  PubMed  Google Scholar 

  3. Kaufman J, DeLorenzo C, Choudhury S, Parsey RV. The 5-HT1A receptor in major depressive disorder. Eur Neuropsychopharmacol. 2016;26:397–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hensler JG. Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration. Life Sci. 2003;72:1665–82.

    Article  CAS  PubMed  Google Scholar 

  5. Jacobsen JP, Siesser WB, Sachs BD, Peterson S, Cools MJ, Setola V, et al. Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. Mol Psychiatry. 2012;17:694–704.

    Article  CAS  PubMed  Google Scholar 

  6. Ruhe HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry. 2007;12:331–59.

    Article  CAS  PubMed  Google Scholar 

  7. Bel N, Artigas F. Reduction of serotonergic function in rat brain by tryptophan depletion: effects in control and fluvoxamine-treated rats. J Neurochem. 1996;67:669–76.

    Article  CAS  PubMed  Google Scholar 

  8. van der Plasse G, Meerkerk DT, Lieben CK, Blokland A, Feenstra MG. Lack of evidence for reduced prefrontal cortical serotonin and dopamine efflux after acute tryptophan depletion. Psychopharmacology. 2007;195:377–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Stancampiano R, Melis F, Sarais L, Cocco S, Cugusi C, Fadda F. Acute administration of a tryptophan-free amino acid mixture decreases 5-HT release in rat hippocampus in vivo. Am J Physiol. 1997;272:R991–994.

    CAS  PubMed  Google Scholar 

  10. Brand T, Anderson GM. The measurement of platelet-poor plasma serotonin: a systematic review of prior reports and recommendations for improved analysis. Clin Chem. 2011;57:1376–86.

    Article  CAS  PubMed  Google Scholar 

  11. Borup C, Petersen IM, le Fevre Honore P, Wetterberg L. Reduction of whole blood serotonin in depressed patients treated with a new, selective serotonin-uptake inhibitor, femoxetine. Psychopharmacology. 1979;63:241–3.

    Article  CAS  PubMed  Google Scholar 

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The article was fully authored by JPRJ.

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Correspondence to Jacob Pade Ramsøe Jacobsen.

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Competing interests

The author is a full-time employee of Evecxia Therapeutics, a company developing drugs for depression and other psychiatric diseases, and owns stock in the company.

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Jacobsen, J.P.R. Serotonin and depression—an alternative interpretation of the data in Moncrieff et al.. Mol Psychiatry 28, 3158–3159 (2023).

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