Low serotonin levels in the brain cause depression

The argument

Depression is linked to a wide range of neurotransmitters; but, the main culprit is serotonin –an inhibitory neurotransmitter. Serotonin pathways have the function of regulating mood, sleep, and cognition. The serotonin hypothesis states that depression results from a chemical imbalance in serotonin levels/low levels of serotonin. Antidepressants in the form of selective serotonin reuptake inhibitors (SSRI) block the reuptake process of serotonin. This blockage results in an increased amount of serotonin in the synaptic gap. The theory is that this increases serotonergic nerve activity leading to improvement in mood. The effectiveness of SSRI drugs such as Prozac and Paxil has been taken as indirect support for the serotonin hypothesis. For example, Elkin et al. have demonstrated that the drug imipramine was successful in treating depressed patients compared to the placebo group. Additionally, Caspi et al. (2003) reveal a potential link to serotonin. The study concluded that specific alleles of the 5-HTT gene increase the vulnerability to depression. Since this gene is responsible for serotonin transmission, the study supports the serotonin hypothesis to a certain extent.

Premises

Counter-arguments

The theory has bidirectional ambiguity. It is not clear whether the level of serotonin caused depression or the depression caused the lower levels of serotonin. Antidepressant drugs increase levels of serotonin in the brain immediately. However, most people do not report feeling better for 3-4 weeks after taking the drugs. If depression was only about serotonin levels, it should not have taken so long for improvements in the mood to take place. Additionally, antidepressants only seem to be effective for about 60% of people. If depression was caused by a lack of serotonin, antidepressants should have been effective for everyone. According to Lacasse and Leo (2005), taking the alleged effectiveness of SSRIs as evidence for the serotonin hypothesis is an example of backward reasoning. Assumptions about the causes of depression are based on how people respond to a treatment, which is logically problematic. Kirsch et al. (2002) found that there was a publication bias in research on the effectiveness of SSRI in depression. If the results of all studies were pooled out, it would seem that the placebo effect accounted for 80% of the anti-depressant response. Of the studies funded by pharmaceutical companies, 57% failed to show a statistically significant difference between an anti-depressant and a neutral placebo. This study hence casts doubt on the serotonin hypothesis.

Rejecting the premises

[Rejecting P1] The hypothesis is stated as though established. Serotonin's role in mood regulation is well attested; the further claim that depression consists in low serotonin has not been demonstrated, and no clinical measure of a patient's brain serotonin exists against which a diagnosis is ever made. Recent large reviews of the available evidence have not found consistent support for the deficiency account. [Rejecting P2] Both supports point in a weaker direction than claimed. Inferring a cause from a treatment's effect is unreliable — that a drug raising synaptic serotonin helps some patients shows a serotonin deficit no more than aspirin's working shows a headache is an aspirin deficit — and the counter names the specific problem: reuptake is blocked within hours while symptoms improve over weeks. The Caspi finding is a gene-environment interaction that has not replicated in subsequent large studies, and it concerns vulnerability rather than a chemical imbalance. [Rejecting C] The conclusion also asks one mechanism to carry an entire etiology. Biological etiology could be argued from several other lines of evidence, and tying the position to the serotonin account attaches it to the weakest of them.