Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms.

G Bagdy,I M Anderson,N Eszlari,X Gonda,G Juhasz,J F W Deakin,D Kovacs

doi:10.1038/tp.2016.57

G Bagdy, I M Anderson + Show 5 more

Open Access

https://doi.org/10.1038/tp.2016.57

Copy DOI

Abstract

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.

Highlights

Genetic variation in the serotonin transporter is one of the most widely studied risk factors for depression since the original observation of its association with neuroticism and interaction with life events.[1,2] its precise role in the development of depression and in mediating the effects of life events is still controversial in spite of a large number of studies. 5-HTTLPR is a functional repeat length polymorphism influencing serotonin reuptake efficiency and serotonin availability in the synaptic cleft in the central nervous system
We demonstrated a less connectivity of the hippocampus and the amygdala with a wide marked interaction between life events related to illnesses and injury (RLE-illness) and 5-HTTLPR genotype, which was only network of several brain regions and grey matter structural characteristics was reported.[48]
It is noteworthy that in our study we found no significant main effect for the 5-HTTLPR genotype in the development of depressive symptoms in the combined sample from Budapest and Manchester, a weak but significant association was detected only in the Budapest sample according to the recessive model

Summary

Introduction

Genetic variation in the serotonin transporter is one of the most widely studied risk factors for depression since the original observation of its association with neuroticism and interaction with life events.[1,2] its precise role in the development of depression and in mediating the effects of life events is still controversial in spite of a large number of studies. 5-HTTLPR is a functional repeat length polymorphism influencing serotonin reuptake efficiency and serotonin availability in the synaptic cleft in the central nervous system. When categorised into early childhood and recent life events, an association between the 5-HTTLPR s allele and early-life adversities, but not recent life events, was found with depression.[15,16,17,18,19,20] Early-childhood adverse experience is proposed to exert a long-lasting impact on neurodevelopment through influencing serotonergic neurotransmission in neural circuits responsible for mood regulation This increases the vulnerability to the negative effects of early stressors,[21,22,23] as well as causing other possible structural and functional changes, including alterations in the programming of glucocorticoid, noradrenergic and vasopressinergic stress response systems. As a result these systems are hypothesised to show a long-lasting over-reaction to new stressors, leading to significantly impaired hippocampus and amygdala development.[24,25,26]

Objectives

Methods

Findings

Conclusion