TY - JOUR

T1 - Effects of Stress and Genetic Predisposition on Symptoms of Psychopathology

AU - Knyazev, G. G.

AU - Bocharov, A. V.

AU - Savostyanov, A. N.

AU - Proshina, E. A.

N1 - Acknowledgments: the authors received fi nancial support for preparation of this article from the Research Institute of Neuroscience and Medicine budget, Topic No. AAAAA21121011990039-2, and the Russian Foundation for Basic Research (Project No. 20-013-00404).

PY - 2023/1

Y1 - 2023/1

N2 - Data in the literature suggest that the presence of the S allele of the serotonin transporter gene (5-HTTLPR) is associated with an increased risk of developing depression in individuals who have experienced the effects of stress in the recent past. However, there are many reports, including meta-analyses, which do not confirm this association. This inconsistency in results can be partly explained by the fact that the association between 5-HTTLPR polymorphisms, stressful life events, and symptoms of mental disorders may not be so direct and obvious. Here we report our analysis of the mechanisms of interaction of the 5-HTTLPR polymorphism with the level of stressful life events in terms of their influence on the onset of symptoms of mental disorders using intermediate variables regarded as indicators of resting state network connectivity and means of regulating the emotions. Cerebral responses to increased levels of stress were found not to differ in carriers of different alleles of the serotonin transporter gene, though these reactions could reduce the likelihood of depression in carriers of the LL genotype, and, conversely, provoke depression in carriers of the S allele. This difference is explained by the fact that carriers of the LL genotype tend to rethink stressful situations in a less negative light, which prevents the emergence of psychopathology, while stress reactions in carriers of the S allele are accompanied by the appearance of repetitive obsessive thoughts and futile attempts to suppress them, which can ultimately lead to depression.

AB - Data in the literature suggest that the presence of the S allele of the serotonin transporter gene (5-HTTLPR) is associated with an increased risk of developing depression in individuals who have experienced the effects of stress in the recent past. However, there are many reports, including meta-analyses, which do not confirm this association. This inconsistency in results can be partly explained by the fact that the association between 5-HTTLPR polymorphisms, stressful life events, and symptoms of mental disorders may not be so direct and obvious. Here we report our analysis of the mechanisms of interaction of the 5-HTTLPR polymorphism with the level of stressful life events in terms of their influence on the onset of symptoms of mental disorders using intermediate variables regarded as indicators of resting state network connectivity and means of regulating the emotions. Cerebral responses to increased levels of stress were found not to differ in carriers of different alleles of the serotonin transporter gene, though these reactions could reduce the likelihood of depression in carriers of the LL genotype, and, conversely, provoke depression in carriers of the S allele. This difference is explained by the fact that carriers of the LL genotype tend to rethink stressful situations in a less negative light, which prevents the emergence of psychopathology, while stress reactions in carriers of the S allele are accompanied by the appearance of repetitive obsessive thoughts and futile attempts to suppress them, which can ultimately lead to depression.

KW - 5-HTTLPR

KW - EEG

KW - depression

KW - emotion regulation

KW - reappraisal

KW - resting state networks

KW - ruminations

KW - stress

KW - suppression

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85149957950&origin=inward&txGid=efdcc0a7018c4cca4c2f1463b0ca51dd

UR - https://www.mendeley.com/catalogue/97d88cc7-7f6d-32a3-aab7-9cb9d5e7bb12/

U2 - 10.1007/s11055-023-01392-x

DO - 10.1007/s11055-023-01392-x

M3 - Article

VL - 53

SP - 70

EP - 80

JO - Neuroscience and Behavioral Physiology

JF - Neuroscience and Behavioral Physiology

SN - 0097-0549

IS - 1

ER -