The Return of Fear: Variation of the Serotonin Transporter Gene Predicts Outcome of a Highly Standardized Exposure-Based One-Session Fear Treatment

Abstract

Background: Methodological problems of existing research, such as the application of unstandardized treatments in heterogeneous samples, has hampered clear conclusions about the extent and direction to which allelic variation of the serotonin transporter gene-linked polymorphic region (5- HTTLPR) is associated with a differential response to psychological treatment. The present study aimed to investigate the effects of the 5-HTTLPR genotype on treatment outcome under highly standardized environmental conditions. Methods: We treated 222 medication-free adults highly fearful of spiders, dental surgeries or blood, injuries and injections with a highly standardized exposure-based 1-session treatment and genotyped them for the 5-HTTLPR. Participants' subjective fear was assessed before, immediately after treatment and at 7 months of follow-up. Results: There were no differences between 5-HTTLPR genotypes in treatment outcome effects at the immediate posttreatment assessment. However, we observed a highly significant genotype × treatment effect (p = 0.004) at the 7-month follow-up. Fear levels of homozygous S allele carriers differed from those heterozygous (p = 0.026) and homozygous (p = 0.012) for the L allele. Compared to posttreatment assessment, LL allele carriers exhibited a further fear decrease at the follow-up assessment. In contrast, SS allele carriers displayed a strong return of fear. Conclusions: Results suggest that genetic variation of the serotonin transporter is associated with differential stability of inhibitory learning processes, potentially reflecting heightened susceptibility for context-related processes that facilitate a return of fear in S allele carriers. If replicated, results suggest the 5-HTTLPR might represent a biomarker for the long-term outcome of brief exposure-based fear treatments and might inform genotype-based selection of psychotherapeutic interventions.

The role of epigenetics for understanding mental health difficulties and its implications for psychotherapy research

“…Epigenetic features might be used in the same fashion to predict outcome as in therapy genetics approaches, where DNA sequence variation is the biological predictor variable (Bakermans‐Kranenburg & van IJzendoorn, ; Eley, ; Wannemuller, Moser, Kumsta, Johren, & Margraf, ). The studies outlined above mark the start of attempts to identify such epigenetic therapy biomarkers.…”

The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies

“…In another clinical study by Wannemueller et al [ 147 ], researchers hypothesized that S allele carriers suffering from phobia might exhibit different response to exposure-based treatments. The study involved verbally assessing the level of fear related to phobic stimuli at different time points (before, immediately after treatment and at 7 months follow up).…”

Genetik und Epigenetik in der Psychotherapie von Depression und Angststörungen

“…Empfehlenswert wäre daher eine Zusammenarbeit verschiedener Forschergruppen, die ihre Patientengruppen unter der Voraussetzung aggregieren, dass die therapeutische Intervention unter hoch-standardisierten Bedingungen erfolgt, um einheitliche methodische Voraussetzungen zu schaffen. In einer kürzlich veröffentlichten Studie von Wannemüller et al [2018] wurde genau diesem Aspekt besondere Beachtung geschenkt. 222 nicht-medizierte Patienten mit unterschiedlichen situativen Ängsten durchliefen eine standardisierte Ein-Sitzungs-Großgruppenbehandlung.…”