Platelet serotonergic markers as endophenotypes for obsessive-compulsive disorder.

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Obsessive-compulsive disorder (OCD) has a known genetic component, but its specific genetic basis is unclear.
• Investigating biological markers in unaffected relatives can help identify genetic vulnerability factors.
• Peripheral serotonergic disturbances are common in OCD patients.

Purpose of the Study:

• To determine if peripheral serotonergic abnormalities in OCD patients are also present in their unaffected parents, suggesting they could be endophenotypes.
• To investigate whole blood serotonin (5-HT) concentration, platelet 5-HT transporter (5-HTT) and 5-HT2A receptor binding, and platelet inositol trisphosphate (IP3) content.
• To explore the familial origin and potential endophenotypic role of these serotonergic disturbances in OCD.

Main Methods:

• Assessed whole blood 5-HT, platelet 5-HTT and 5-HT2A receptor binding, and platelet IP3 content in OCD probands (n=48), their unaffected parents (n=65), and controls (n=113).
• Compared these peripheral serotonergic markers between OCD patients, their parents, and control groups.
• Analyzed correlations within families for whole blood 5-HT concentration.

Main Results:

• OCD patients and their unaffected parents showed lower whole blood 5-HT, fewer platelet 5-HTT binding sites, and higher platelet IP3 content compared to controls.
• Whole blood 5-HT concentration demonstrated a significant correlation within families.
• Increased 5-HT2A receptor number and affinity were observed in parents but not in OCD probands, distinguishing affected and unaffected individuals.

Conclusions:

• Peripheral serotonergic abnormalities are present in both OCD patients and their unaffected parents, supporting a familial basis for these disturbances.
• These alterations may function as endophenotypic markers for OCD.
• The findings contribute to understanding the biological mechanisms and genetic underpinnings of OCD.