5-HT1A and 5-HT2A Signaling, Desensitization, and Downregulation: Serotonergic Dysfunction and Abnormal Receptor Density in Schizophrenia and the Prodrome

The significant role of serotonin (5-hydroxytryptamine [5-HT]) in the pathogenesis and early development of schizophrenia has been established by contemporary research through the assessment of structural and pharmacological neuroimaging, blood metabolites, cerebrospinal fluid, genome polymorphisms, and other valid indicators of abnormal serotonergic activity in prodromal, ultra-high-risk, and schizophrenic patient groups. A modern approach toward understanding the complex psychophysiology behind schizophrenia will be outlined through the demonstration of 5-HT(1A) and 5-HT(2A) receptors as key modulators within the spectrum of negative symptoms associated with schizoaffective disorders, including a variety of disturbances in cognition, behavior, mood, social function, perception of reality, and hormonal response to stressors. This paper will review the evidence for attributing the risk of schizophrenia onset to early defects in serotonergic neurotransmission and explore the perspective of selective serotonin receptor inhibitor (SSRI) pharmacotherapy as a method of treatment and intervention for prodromal and ultra-high-risk patients by increasing 5-HT(1A )receptor sensitivity levels and modifying the transcription of 5-HT(1A) receptor-associated gene expression in these groups.