Serotonin

Serotonin

Serotonin (5-hydroxytryptamine) is a neurotransmitter that is primarily involved in mood regulation. The neuromodulator is best known for its involvement in depression, although its malfunction has also been implicated in other psychiatric conditions, such as Generalized Anxiety Disorder, Obsessive-Compulsive Disorder, Attention-Deficit Hyperactivity Disorder, Borderline Personality Disorder, Post-Partum Blues, Autism, eating disorders, panic attacks, phobias and even Schizophrenia (an affliction also involving dopamine overabundance).

Patients with Major Depressive Disorder produce less serotonin as measured by neuroimaging techniques, and this finding is the basis for the common medications used to treat depression, selective serotonin reuptake inhibitors (SSRI). Perhaps the most famous SSRI is fluoxetine, brand name Prozac. The production of serotonin may depend on whether the individual is homozygous (two copies) or heterozygous (one copy) of the 5-HT short allele, homozygotes are more likely to succumb to depression even if under the same stressful circumstances than heterozygotes or those who have not inherited that allele at all (Caspi et al., 2003). Individuals with two copies of the long 5-HT allele are the least prone to developing the illness. Notwithstanding, in their meta-analysis across studies, Risch et al. (2009) found little evidence supporting this result.

According to Nugent et al. (2008), severe tryptophan depletion leads to a relapse of depressive symptoms. Tryptophan is an essential amino acid found in aliments such as pasta and turkey and a precursor to serotonin synthesis. In the experiment, subjects returned to normal as soon as tryptophan was reincorporated into their diet.

In their review of findings, Russo et al. (2009) cite several authors that have attested to serotonin mediating sleep, aggression, anxiety, thermoregulation, satiety and stress, Curiously, neurogenesis also seems to depend on serotonin. The reviewers also explain the brain reaction to low tryptophan blood plasma levels and “speculate about the possible survival value of this mechanism” (259).

Neurogenesis is the appearance of new brain cells (neurons) and Banasr et al. (2004) found that adult neurogenesis is enhanced by serotonin agonists (agonists stimulate, antagonists inhibit). Several receptor subtypes are implicated in the process, and the scientists came to the conclusion that serotonin was beneficial to adult cell proliferation, especially in the following brain regions: subgranular layer (SGL), subventricular zone (SVZ), dentate gyrus (DG) and olfactory bulb. A small reminder that gyrus (plural form gyri) refers to convex parts of the brain surface gray matter, while sulci (singular form sulcus) denote concave parts.

Dayan et al. (2008) suggest that serotonin deficiency mitigates impulse control by lowering inhibition, thus making the action with potentially adverse consequences more likely. The authors also discuss serotonergic pathways’ implication in thought processes related to aversive thought processes. Recalling that in encountering a new stimulus, an organism is often faced with an internal aversion versus approach conflict, the decision resting on whether the object in question poses a threat or promises a reward, respectively.

“Most people are about as happy as their self confidence will allow them to be.” (Shannon L. Alder). Illustration : Megan Jorgensen.

References:

• Banasr, M., Hery, M., Printemps, R. & Daszuta, A. (2004). Neuropsychopharmacology, 29 (3): 450-60.
• Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, HL., McClay, J., Mill, J., Martin, J., Braithwaite, A. & Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301 (5631): 386-9.
• Dayan, P.  & Huys, Q. J. M. (2008). Serotonin, inhibition and negative mood. PLoS Computational Biology, 4 (2): 0001-11.
• Nugent, A. C, Neumeister, A., Goldman, D., Herscovitch, P., Charney, D. S. & Drevets, W. C. (2008). Serotonin transporter genotype and depressive phenotype determination by discriminant analysis of glucose metabolism under acute tryptophan depletion. Neuroimage, 43(4): 764–774
• Risch, N., Herrell, R., Lehner, T., Liang, K. -Y., Eaves, L., Hoh, J., Griem, A., Kovacs, M., Ott, J. & Merikangas, K. R. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events and risk of depression: A meta-analysis. JAMA, 301(23): 2462–2471.
• Russo, S., Kema, I. P., Bosker, F., Haavik, J. & Korf, J. (2009). Tryptophan as an evolutionary conserved signal to brain serotonin: Molecular evidence and psychiatric implications. The World Journal of Biological Psychiatry, 10: 258-68.