Benedetta Vai1, Alessandro Serretti2, Sara Poletti3, Mattia Mascia4, Cristina Lorenzi4, Cristina Colombo3, Francesco Benedetti3. 1. Psychiatry and Clinical Psychobiology, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy; University Vita-Salute San Raffaele, Milano, Italy; Fondazione Centro San Raffaele, Milano, Italy. Electronic address: vai.benedetta@hsr.it. 2. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy. 3. Psychiatry and Clinical Psychobiology, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy; University Vita-Salute San Raffaele, Milano, Italy. 4. Psychiatry and Clinical Psychobiology, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy.
Abstract
BACKGROUND: In bipolar disorder (BD) the risk of suicide in adult life can be influenced by the interaction of adverse childhood experiences with the serotonin transporter polymorphism (5-HTTLPR). The cortico-limbic connectivity is a candidate endophenotype for the disorder, also related to suicidality and affected by the 5-HT system. METHODS: In 64 (*s carriers = 41; l/l = 23) depressed BD patients, we explored the effect of 5-HTTLPR on corticolimbic functional connectivity (FC) during emotional processing, and the role of FC in moderating/mediating the effect of early stressful events on suicidality among 5-HTTLPR groups, by implementing Generalized Structural Equation Model. RESULTS: 5-HTTLPR affects FC between amygdala (Amy) and anterior cingulate cortex (ACC), temporal pole, putamen/thalamus, and precuneus. The short allele was associated to a more inefficient corticolimbic connectivity. In 5-HTTLPR*s carriers, but not in l/l, the Amy-ACC functional coupling mediated the relationship between stress load and current suicidality. LIMITATIONS: Patients were not drug-naive, and the recruitment took place in a single center, thus raising the possibility of population stratifications. The sample size is relatively small, but our findings can provide the background for replication study in independent and larger datasets. CONCLUSIONS: Our results confirm the link between the 5-HTT promoter polymorphism and susceptibility to stress in BD, and suggest that cortico-limbic functional connectivity mediates these effects. This pattern could identify a vulnerability factor for the exacerbation of mood episodes after stressful life events particularly relevant in *s carriers.
BACKGROUND: In bipolar disorder (BD) the risk of suicide in adult life can be influenced by the interaction of adverse childhood experiences with the serotonin transporter polymorphism (5-HTTLPR). The cortico-limbic connectivity is a candidate endophenotype for the disorder, also related to suicidality and affected by the 5-HT system. METHODS: In 64 (*s carriers = 41; l/l = 23) depressedBDpatients, we explored the effect of 5-HTTLPR on corticolimbic functional connectivity (FC) during emotional processing, and the role of FC in moderating/mediating the effect of early stressful events on suicidality among 5-HTTLPR groups, by implementing Generalized Structural Equation Model. RESULTS:5-HTTLPR affects FC between amygdala (Amy) and anterior cingulate cortex (ACC), temporal pole, putamen/thalamus, and precuneus. The short allele was associated to a more inefficient corticolimbic connectivity. In 5-HTTLPR*s carriers, but not in l/l, the Amy-ACC functional coupling mediated the relationship between stress load and current suicidality. LIMITATIONS: Patients were not drug-naive, and the recruitment took place in a single center, thus raising the possibility of population stratifications. The sample size is relatively small, but our findings can provide the background for replication study in independent and larger datasets. CONCLUSIONS: Our results confirm the link between the 5-HTT promoter polymorphism and susceptibility to stress in BD, and suggest that cortico-limbic functional connectivity mediates these effects. This pattern could identify a vulnerability factor for the exacerbation of mood episodes after stressful life events particularly relevant in *s carriers.
Authors: Anjali Sankar; Dustin Scheinost; Danielle A Goldman; Rebecca Drachman; Lejla Colic; Luca M Villa; Jihoon A Kim; Yarani Gonzalez; Imani Marcelo; Mei Shinomiya; Brian Pittman; Cheryl M Lacadie; Maria A Oquendo; R Todd Constable; Hilary P Blumberg Journal: Transl Psychiatry Date: 2022-01-10 Impact factor: 7.989