Elevated serotonin may cause schizophrenia and bipolar disorder

The study and even the popular press article are fairly technical so I won’t go into the full details here but I will just give a TLDR. Namely, the study below provides strong evidence that lower levels / expression / activity of the serotonin transporter (SERT) protein is likely a direct cause of schizophrenia, bipolar disorder, and even anxiety. Considering that lower SERT levels / expression / activity means elevated extracellular serotonin levels, a simpler way of stating the same is that elevated serotonin is likely the major cause behind schizophrenia, bipolar disorder and anxiety, which together cover at least 80% of the mental health diagnoses doled by psychiatrists. Of course, the article and the study are very careful to not directly mention the phrases “elevated serotonin” and “mental illness” in the same body of text but in light of the main physiological role of SERT the message is quite clear. Keep in mind that the SERT protein is the main target of the (in)famous SSRI drugs – i.e. they are potent inhibitors of SERT. As such, I will say what no doctor currently dares to – SSRI drugs may very well be behind the current epidemic of mental disorders in the Western world awash in this serotonergic poison.



“…SERT regulates the concentration of the neurotransmitter serotonin within the gap between neurons where neurotransmitters are exchanged (the synaptic cleft). It is considered to be deeply involved with mental illnesses, and drugs targeting the protein are widely used as treatments for depression and . In particular, a polymorphism called 5-HTTLPR in the gene that encodes SERT has been a target for many mental disorder studies. When the polymorphism is the L (long) type, more SERT is produced, and when it is the S (short) type, less is produced. People generally have one combination of these types, L/L, S/L, or S/S. In 2003, an analysis (Capsi et al., 2003) became highly regarded for reporting that people with the S-type polymorphism had a stronger tendency for anxiety and were more susceptible to depression.”

“…Furthermore, a detailed analysis of the SERT gene polymorphism 5-HTTLPR revealed that the methylation rate was high in patients with bipolar disorder and schizophrenia when 5-HTTLPR was hypoactive type (S/S or S/L). When the CpG3 site of the SERT gene was artificially methylated, researchers found that the transcriptional activation ability and production of the SERT protein were both markedly suppressed.”

“…Researchers also investigated the volume of the amygdala with MRI images from 41 healthy subjects and 57 schizophrenia age- and gender-matched patients. The amygdala is a part of the brain that, among other functions, plays a major role in emotional responses. SERT actions are strong there and its association with DNA methylation has been reported in the past. The volume of the left amygdala of male patients with hypoactive type 5-HTTLPR polymorphism was found to have an inverse correlation with the DNA methylation rate of CpG3. This suggests that male schizophrenia patients of this polymorphism type may have a hypermethylated SERT gene that leads to decreased amygdala volume through decreased SERT protein levels.”

“Our research shows that a specific site in the SERT gene is hypermethylated in  with schizophrenia and bipolar disorder, and is associated with volume changes in the amygdala,” said study leader, Dr. Kazuya Iwamoto. “In the future, we believe that this can be used as a biomarker for onset prediction, diagnosis, and to assess therapeutic effects. It could even be a clue for the molecular pathologies of these .”