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Serotonin hypothesis (1967)

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  • Serotonin hypothesis (1967)

Although not a "key study," the Serotonin Hypothesis (also known as the 5-HTT Hypothesis) is a key theory used to explain the origins of depression.  Coppen's (1967) original theory argued that a deficit in 5-HTT was the primary cause of depression. His theory was based on finding low levels of metabolites of serotonin in the cerebrospinal fluid of depressed patients. The modern theory argues that dysfunctions of serotonergic neurons early in life, whether increased or decreased, can influence brain development as well as affect sensitivity to aversive stressors and, more generally, emotion regulation in adults.

Support for the theory
  • Rausch et al (1985) 18 subjects were either administered physostigmine (a serotonin antagonist) or a placebo in a double-blind study. In comparison to placebo, the drug caused a significant depression in mood, as measured by self- and observer-rated depression scores.
  • Altering serotonin levels by diet (neurotransmission depletion studies) led to depressive symptoms in formerly depressed patients (Moreno and Delgado 2000)
  • Caspi found a correlation between a variation of the 5HTT gene (the serotonin transporter gene) and levels of depression in combination with stressful life experiences.
  • Ansorge et al (2004) SERT (5-HTT, the serotonin transporter gene) found that knockout rats express a depressive- and anxiety-related behavioural phenotype similar to adult humans.
  • Some patients respond positively to SSRIs which increase the level of serotonin in synapses.

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Limitations of the theory

  • There have been mixed results with neurotransmitter depletion studies in non-depressed individuals.
  • Animal research may not be a good model for depressed human patients.
  • We cannot directly measure serotonin in the brain.
  • Not all people with depression are successfully treated with SSRIs.  The generally accepted success rate is between 20 and 30% of all patients.
  • Cognitive symptoms of depression cannot be explained by low levels of serotonin
  • There appears to be a correlation between depression and hippocampal atrophication (Videbech, 2004). This is better explained by the cortisol hypothesis. 

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