University College London: Serotonin Has Little or Nothing to Do with Depression

Depressive disorder is one of the common mental disorders. Others include anxiety disorders, post-traumatic stress disorders, and eating disorders. Depression is the commonest mood disorder. Its major symptoms include reduced energy, reduced interest, and a persistent low mood. Other symptoms are hopelessness, feelings of guilt, and disturbed appetite.

Depressed Person

Depressed Person

Factors like illness, social problems, and adverse childhood occurrences are big contributors to depression. There is a higher prevalence in females also. This may be due to hormonal causes, socialization patterns, and coping styles. Heritability of depression has also been reported.

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Some theories have been proposed concerning the etiology of depression. They include monoamine theory, endocrine theory, and genetic theory. The monoamine theory proposes that a reduction in serotonin, norepinephrine and dopamine neurotransmitters is the cause of depression. Hence, anti-depressants like selective serotonin reuptake inhibitors, serotonin-noradrenaline reuptake inhibitors, and tricyclic anti-depressants have been used in the management of depression.

Is there any truth to the monoamine theory?

A review of previous research was done by University College London scientists. They discovered no clear linkage between depression and levels of serotonin.

This review, which spanned many decades, included important research that has been published on the connection that exists between depression and serotonin (5HT). The number of research participants in the various reviewed studies was significant.

One of the reviews was on studies that deprived people of an amino acid diet which is useful in serotonin production. It was discovered that many of the research subjects did not come down with depression from the diet-induced serotonin deficiency. However, in a smaller group with less than a hundred subjects that had a history of depression in their family, a very weak relationship was discovered.

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In another study, there was no significant difference in 5HT levels in the brain fluids and blood people that had depressed subjects and their non-depressed counterparts. When studies were done on the transporter and receptors of serotonin, the weak and inconsistent result showing greater 5HT activity in depressed persons was discovered. This may be due to antidepressant usage as stated by the researchers.

There was no gene variation detected in depressed patients as well as their healthy counterparts when a large population was studied. Larger research proved the prominent early study that linked depression to stressful life happenings and the nature of the 5HT transporter gene, to be false. However, a strong linkage was found to exist between stressful life occurrences and the risks of becoming depressed. Also, lower levels of 5HT were noted among participants who used antidepressants in another analysis. This was explained by the researchers to be a result of counteracting effects from changes in the brain to compensate for long drug use periods.

With the above research results, there is advocacy by the UCL scientists, to venture into other ways of treating depression like psychotherapy, improving living standards, and appropriate management events of life that might cause people to be depressed. Since antidepressants are also associated with symptoms of withdrawal, there is a need to reduce the frequency of their prescription. Further studies need to be conducted on the potency of antidepressants also.

Clinical significance

Depression is one of the major contributors to the global burden of disease. It cuts across various races and ethnicities. Since it is a common illness, it is expedient to get adequate ways of treating it as well as improving the quality of life of the patients.

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Since antidepressants have withdrawal symptoms, it is important to review their benefits, hence this study. From the findings, it has been discovered that 5HT levels have little connection with depression, as such, there may be little need for these drugs in depression management. This calls for a study into the benefits of antidepressants as well as exploring other management options.


Adequate depression management is an important aspect of health that will improve the quality of life of patients. From this study, it was noted that the use of antidepressants had little or no benefits in depression management. Therefore, there is a need for further studies on the benefits of antidepressants in addition to other management options for depression.


The serotonin theory of depression: a systematic umbrella review of the evidence



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