Depression and suicidal conduct have both been linked to the serotonin 1A (5-HT1A) receptor. Lower resting cortisol levels are connected with increased 5-HT1A receptor binding, and both distinguish suicide attempters from those suffering from depression. However, it was unclear whether 5-HT1A receptor binding and cortisol responses to stress were linked to family susceptibility and resistance to suicide behavior.

[11C]CUMI-101 positron emission tomography imaging was performed on people judged to be at high risk for mood disorder or suicidal behavior due to having a first- or second-degree relative(s) with an early onset mood disorder and a history of suicidal behavior. The high-risk individuals were divided into 3 groups: high risk resilient with no history of mood disorder or suicidal behavior (n=29); high risk with a history of a mood disorder but no history of suicidal behavior (n=31); and high risk with a history of mood disorder and suicidal behavior (n=25). The groups were compared to healthy volunteers (n=34) who had no family history of mood disorder or suicidal conduct. The Trier Social Stress Task (TSST) was completed by the participants. At the time of the TSST and PET scans, the subjects were not using any psychiatric medicines.

Researchers found no group differences in 5-HT1A receptor binding when all areas were considered at the same time, nor did they find group heterogeneity among regions. The findings were consistent across outcome measures (BPND for all participants and BPp for a portion of the sample) and region of interest criteria (ROIs; standard or serotonin system-specific ROIs). They also discovered no group differences in TSST results. Lower BPp binding (β=0.084, SE=0.038, P=.048) and greater cortisol response to stress (β= 9.25, 95% CI [3.27,15.23], P=.004) were linked with more lethality attempts in the high risk with mood disorder and suicide behavior group. There were no statistically significant links between 5-HT1A binding and cortisol results.

Although it might be associated with the lethality of suicide attempts, 5-HT1A receptor binding in ROIs was not linked to family risk or resistance guarding against suicidal behavior or mood disorder. More research was needed to better understand the molecular mechanisms involved in familial suicide behavior risk and how the hypothalamic-pituitary-adrenal axis impacted such risk.