Serotonin & Schizophrenia

The finding that atypical antipsychotics block serotonin as well as dopamine receptors suggests that serotonin also plays a role in the pathophysiology and treatment of schizophrenia. Although many serotonin receptor subtypes are located along serotonergic pathways of the brain, 5-HT1 and 5-HT2 receptors are of particular interest. For example, some atypical antipsychotics are potent antagonists of 5-HT2 receptors. In addition to reducing psychotic symptoms, these agents cause fewer EPS effects and may improve cognitive deficiencies in schizophrenia. Current interest in serotonin receptors has focused on 5-HT1A and 5‑HT2A receptors. 5-HT1A receptors are located in the hippocampus and are believed to be autoreceptors. 5-HT2A receptors may be important for several reasons, including :

• Differences in their affinity to 5-HT2A receptors may explain variations between the therapeutic effects and side-effect profiles of different antipsychotics.
• Variations in the gene for 5-HT2A receptors may be a minor risk factor for schizophrenia.
• Some researchers have found fewer 5-HT2A receptors expressed in the frontal cortex of patients with schizophrenia.

In addition, as suggested by research involving mood disorders, serotonin may play a role in the suicidal and impulsive behavior of people with schizophrenia. While the exact function of serotonin in schizophrenia is unclear, the evidence that it plays some role is strong. For example, when atypical antipsychotics block 5-HT2A receptors in the prefrontal cortex, the resulting increases in serotonin and dopamine are associated with improvement in cognition. In the nigrostriatal pathway, the increases are associated with reduced EPS