Symptom's Associated with Abnormal Serotonin Levels

From brainmatrix

Note of Relevance for Functional Medicine: The essential amino acid tryptophan that is found in several foods is the sole precursor to serotonin in the nervous system.1 Tryptophan is found in:1,2

  • Meats
  • Dairy foods
  • Fruits
  • Seeds

The availability of tryptophan is increased with high-glycemic index and high-glycemic load foods and meals.3

Affective Disorders and Mood[edit]

(-) Depression. Serotonin has long been implicated in depression.4–8 Research into the connection between serotonin and depression suggests that serotonin dysfunction may cause depression in certain circumstances and reduced serotonin activity may make it difficult to recover from depression. Serotonin is thought to contribute to negative thinking patterns. Serotonin forms the basis of several depression treatments, including with selective serotonin reuptake inhibitors (SSRI).5, 6,9

(+/-) Anxiety/Panic. Serotonin activity is thought to play a role in panic disorder, and both too much and too little serotonin have been implicated in panic and different forms of anxiety.10–12 The relationship between anxiety and serotonin may in part occur because of the role of serotonin in the stress response.13

(+/-) Mood. Higher levels of serotonin are associated with improved mood, whereas serotonin dysfunction has been linked to suicidal ideation.5,9 Research on menopausal women has shown that changes in serotonin function are implicated in mood alterations in those undergoing estrogen treatment.14

Cognition[edit]

*Serotonin’s role in cognition may involve its interaction with dopamine.15

(+/-) Cognitive Performance. Reduced serotonin neurotransmission appears to have a negative impact on cognitive functions, and normalizing serotonin levels may be beneficial for restoring cognitive performance, particularly in the context of neuropsychiatric disorders.16 However, there are also data that suggest that during the acute phase of SSRI treatment, cognitive dysfunction may occur.17

Serotonin has been implicated in the cognitive symptoms of Alzheimer’s disease (AD), but the specific role that serotonin stimulation could play in influencing these symptoms has not been sufficiently studied.18

(+/-) Learning. Research shows that administering certain serotonin agonists and certain serotonin antagonists can facilitate learning in contexts where cognitive demand is high.1

(-) Memory. Several studies suggest that low extracellular serotonin levels are associated with impairments in the consolidation of memories.19

Behavior[edit]

(+) Impulsivity. Serotonin may be associated with preference for immediate reward and increased impulsivity.209

(+/-) Eating Behavior. Serotonin is implicated in feelings of satiety, and serotonin dysfunction can therefore lead to increases or decreases in appetite that are associated with eating disorders or obesity.9,13,21

(-) Social Adaptation. Serotonin is heavily implicated in social and moral behavior.22 The use of serotonin and norepinephrine reuptake inhibitors (SNRI) in patients with depression has been linked to improvements in social adaptation.9

(+/-) Aggression. Changes in serotonin are linked to aggression, though the specific mechanisms by which serotonin may contribute to aggressive behavior is not entirely understood.12 However, serotonin dysfunction is implicated in feelings of frustration and agitation, which may contribute to aggressive behavior.9

(+/-) Sexual Behavior. Decreased libido has been linked to serotonin dysfunction.9 However, sexual dysfunction is also a common unwanted side effect of SSRIs.12

Physical Symptoms[edit]

*Many physical symptoms of serotonin dysregulation occur due to its role as a hormone, neuromodulator rather than as a neurotransmitter (see relevant hormone document for details).

(+/-) Heart Rate. Serotonin plays a role in the communication between the brain and the heart in those with panic disorder and in those on serotonin reuptake inhibitors. Changes in serotonin levels may therefore be associated with changes in heart rate.11

(+/-) Pain. Serotonin is known to regulate pain, which may occur in part due to interactions with other hormones.16,23,24 Specifically, it may enhance pain sensation through its role as an inflammatory mediator.25 Low central serotonin levels have been implicated in migraine headaches, and triptans, agonists of certain classes of serotonin receptors are the first-line of acute treatment for the disorder.

(+/-) Sleep. Serotonin interacts with the brain systems involved in sleep and waking.26,27 Changes in serotonin levels can have differential effects on wakefulness and fatigue.

(-) Premenstrual syndrome. Serotonin is implicated in premenstrual syndrome (PMS), and serotonin reuptake inhibitors that increase serotonin levels have been shown to improve symptoms.28,29

(+/-) Body temperature. Serotonin helps to regulate body temperature, so changes in body temperature or body temperature regulation may occur with serotonin dysfunction.13

References[edit]

1. Jenkins TA, Nguyen JCD, Polglaze KE, Bertrand PP. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients. 2016;8(1). doi:10.3390/NU8010056

2. Friedman M, Levin CE. Nutritional and medicinal aspects of D-amino acids. Amino Acids. 2012;42(5):1553-1582. doi:10.1007/S00726-011-0915-1

3. Herrera CP, Smith K, Atkinson F, et al. High-glycaemic index and -glycaemic load meals increase the availability of tryptophan in healthy volunteers. Br J Nutr. 2011;105(11):1601-1606. doi:10.1017/S0007114510005192

4. Cowen PJ, Browning M. What has serotonin to do with depression? World Psychiatry. 2015;14(2):158. doi:10.1002/WPS.20229

5. Young SN. How to increase serotonin in the human brain without drugs. Journal of Psychiatry & Neuroscience : JPN. 2007;32(6):394. Accessed April 2, 2022. /pmc/articles/PMC2077351/

6. Blier P, El-Mansari M. Serotonin and beyond: therapeutics for major depression. Philosophical Transactions of the Royal Society B: Biological Sciences. 2013;368(1615). doi:10.1098/RSTB.2012.0536

7. Albert PR, Benkelfat C. The neurobiology of depression—revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies. Philosophical Transactions of the Royal Society B: Biological Sciences. 2013;368(1615). doi:10.1098/RSTB.2012.0535

8. Sansone R, Sansone L. Sunshine, serotonin, and skin: A partial explanation for seasonal patterns in psychopathology? Innovations in Clinical Neuroscience. 2013;10(7-8):20-24.

9. Briley M, Moret C. Improvement of social adaptation in depression with serotonin and norepinephrine reuptake inhibitors. Neuropsychiatric Disease and Treatment. 2010;6:647. doi:10.2147/NDT.S13171

10. Maron E, Shlik J. Serotonin function in panic disorder: important, but why? Neuropsychopharmacology 2006 31:1. 2005;31(1):1-11. doi:10.1038/sj.npp.1300880

11. Mueller EM, Panitz C, Nestoriuc Y, Stemmler G, Wacker J. Panic disorder and serotonin reuptake inhibitors predict coupling of cortical and cardiac activity. Neuropsychopharmacology. 2014;39(2):507. doi:10.1038/NPP.2013.224

12. Olivier B. Serotonin: a never-ending story. Eur J Pharmacol. 2015;753:2-18. doi:10.1016/J.EJPHAR.2014.10.031

13. Kanova M, Kohout P. Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill. International Journal of Molecular Sciences. 2021;22(9):4837. doi:10.3390/IJMS22094837

14. Amin Z, Canli T, Epperson CN. Effect of estrogen-serotonin interactions on mood and cognition. Behav Cogn Neurosci Rev. 2005;4(1):43-58. doi:10.1177/1534582305277152

15. Olvera-Cortés ME, Anguiano-Rodríguez P, López-Vázquez MÁ, Alfaro JMC. Serotonin/dopamine interaction in learning. Prog Brain Res. 2008;172:567-602. doi:10.1016/S0079-6123(08)00927-8

16. Štrac DŠ, Pivac N, Mück-Šeler D. The serotonergic system and cognitive function. Translational Neuroscience. 2016;7(1):35. doi:10.1515/TNSCI-2016-0007

17. Sayyah M, Eslami K, AlaiShehni S, Kouti L. Cognitive Function before and during Treatment with Selective Serotonin Reuptake Inhibitors in Patients with Depression or Obsessive-Compulsive Disorder. Psychiatry Journal. 2016;2016:1-4. doi:10.1155/2016/5480391

18. Schmitt J, Wingen M, Ramaekers J, Evers E, Riedel W. Serotonin and human cognitive performance. Curr Pharm Des. 2006;12(20):2473-2486. doi:10.2174/138161206777698909

19. Cowen P, Sherwood AC. The role of serotonin in cognitive function: evidence from recent studies and implications for understanding depression. J Psychopharmacol. 2013;27(7):575-583. doi:10.1177/0269881113482531

20. Rizvi SJ, Pizzagalli DA, Sproule BA, Kennedy SH. Assessing anhedonia in depression: Potentials and pitfalls. Neurosci Biobehav Rev. 2016;65:21. doi:10.1016/J.NEUBIOREV.2016.03.004

21. Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995;3 Suppl 4. doi:10.1002/J.1550-8528.1995.TB00215.X

22. Siegel JZ, Crockett MJ. How serotonin shapes moral judgment and behavior. Ann N Y Acad Sci. 2013;1299(1):42. doi:10.1111/NYAS.12229

23. Paredes S, Cantillo S, Candido KD, Knezevic NN. An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens. Int J Mol Sci. 2019;20(22). doi:10.3390/IJMS20225729

24. Sommer C. Serotonin in pain and analgesia: actions in the periphery. Mol Neurobiol. 2004;30(2):117-125. doi:10.1385/MN:30:2:117

25. Wang X, Li WG, Yu Y, et al. Serotonin facilitates peripheral pain sensitivity in a manner that depends on the nonproton ligand sensing domain of ASIC3 channel. J Neurosci. 2013;33(10):4265-4279. doi:10.1523/JNEUROSCI.3376-12.2013

26. Ursin R. Serotonin and sleep. Sleep Med Rev. 2002;6(1):55-67. doi:10.1053/SMRV.2001.0174

27. Leu-Semenescu S, Arnulf I, Decaix C, et al. Sleep and rhythm consequences of a genetically induced loss of serotonin. Sleep. 2010;33(3):307. doi:10.1093/SLEEP/33.3.307

28. Yonkers KA, O’Brien PS, Eriksson E. Premenstrual syndrome. Lancet. 2008;371(9619):1200. doi:10.1016/S0140-6736(08)60527-9

29. Marjoribanks J, Brown J, O’Brien PMS, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. The Cochrane Database of Systematic Reviews. 2013;2013(6). doi:10.1002/14651858.CD001396.PUB3