From the Guidelines
The serotonin hypothesis of psychosis suggests that psychotic symptoms can be attributed to excessive serotonergic activity in the brain, particularly through the antagonism of serotonergic receptors, as supported by the use of atypical antipsychotic agents that have a variety of effects, including antagonism of serotonergic receptors 1. According to this hypothesis, an overabundance of serotonin or hypersensitivity of certain serotonin receptors, particularly the 5-HT2A receptors, leads to the development of hallucinations, delusions, and other psychotic symptoms.
- The atypical antipsychotics, which are at least as effective for positive symptoms as traditional agents, work by antagonizing these serotonergic receptors, among other effects 1.
- This theory is also supported by the fact that antipsychotic agents, including traditional neuroleptic medications and atypical antipsychotic agents, are recommended for the treatment of psychotic symptoms associated with schizophrenia 1.
- The interaction between serotonin and dopamine systems is also important, as serotonin can modulate dopamine release, potentially contributing to psychotic symptoms through this indirect mechanism.
- While the serotonin hypothesis provides valuable insights into psychosis, it's now understood that psychotic disorders like schizophrenia involve complex interactions between multiple neurotransmitter systems, including dopamine, glutamate, and GABA, rather than dysfunction in a single neurotransmitter system alone.
From the Research
Serotonin Hypothesis of Psychosis
The serotonin hypothesis of psychosis suggests that psychotic symptoms can be attributed to abnormalities in serotonergic systems. According to the study 2, the fundamental idea that psychotic states seen in psychiatric disorders such as schizophrenia might be attributable, in part, to abnormalities in serotonergic systems began with the almost simultaneous discovery of lysergic acid diethylamide (LSD), psilocybin, and serotonin.
Key Findings
- The study 2 confirms early speculations regarding the important relationship between serotonin and both drug-induced and disorder-based psychotic states.
- Modern biochemical, pharmacological, behavioral, neuroimaging, genetic, and molecular biological sciences are converging to understand how serotonergic systems interact with other monoaminergic and glutamatergic systems to modulate states of consciousness and contribute to psychotic disorders such as the group of schizophrenias.
- The serotonin hypothesis of psychosis is supported by the fact that hallucinogenic drugs that function as agonists at serotonin-2A receptors can induce psychotic states.
Implications
- The serotonin hypothesis of psychosis has implications for the treatment of psychotic disorders, suggesting that targeting serotonergic systems may be an effective approach.
- However, the studies 3, 4, 5, and 6 focus on the effectiveness of antipsychotic medications, such as olanzapine, quetiapine, risperidone, and ziprasidone, in treating psychotic symptoms, rather than specifically addressing the serotonin hypothesis.
- These studies provide evidence for the effectiveness of these medications in reducing psychotic symptoms, but do not directly address the underlying mechanisms, including the role of serotonin.