Polymorphism in the serotonin transporter gene polymorphisms (<i>5-HTTLPR</i>) modifies the association between significant life events and depression in people with multiple sclerosis

Saul, Alice; Taylor, Bruce; Simpson, Steve; Ponsonby, Anne–Louise; Blizzard, Leigh; Dwyer, Terence; McMorran, Brendan J.; Wood, Brenda; Mei, Ingrid van der

doi:10.1177/1352458518770021

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…Although the L variant has been associated with higher levels of SERT gene products and higher reuptake activity, S allele carriers were reported to be more susceptible to depression. 28 , 29 Contrary to the recent report by Saul, et al who found an association between depression severity in patients with MS with one or two copies of the 5-HTTLPR S allele, 30 the frequency of S allele carriers in the present study did not differ significantly between patients with MS who reported feeling depressed and those with normal psychological status (53% vs. 51%). Moreover, the frequency of S allele carriers was lower in patients (31%) than in the control group (47%).…”

Section: Discussioncontrasting

confidence: 99%

Polymorphisms of serotonin transporter gene and psychological status in patients with multiple sclerosis

Farjadian¹,

Fakhraei²,

Niknam³

et al. 2019

CJN

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Background: Multiple sclerosis (MS) is the most common neuroinflammatory disease in young adults. Anxiety and depression may predispose individuals to MS and flare-ups. Serotonin transmission is modified in some brain regions of patients with MS, and these changes may contribute to their psychiatric abnormalities. We studied the frequencies of common polymorphisms of the serotonin reuptake transporter (SERT) gene in patients with MS according to their psychological status. Methods: The 5-HTTLPR, rs25531, and STin2VNTR polymorphisms of the SERT gene were genotyped by polymerase chain reaction (PCR)-based methods in 100 patients with MS and 100 healthy controls. Results: There were no remarkable differences in SERT gene polymorphisms between patients with MS and healthy controls. Unlike the control group, 41% of the patients showed some degree of depression based on Beck Depression Inventory (BDI), but no association was observed between SERT gene polymorphisms after the patients were stratified by depression status. Conclusion: In addition to SERT gene polymorphisms, modulation of serotonin at the synapses may also be regulated by genetic variations in tryptophan hydroxylase type 2 and serotonin receptors. Further studies with functional brain imaging of the serotonergic system in patients with MS can provide information on the role of serotonin in this disease.

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Section: Discussioncontrasting

confidence: 99%

Polymorphisms of serotonin transporter gene and psychological status in patients with multiple sclerosis

Farjadian¹,

Fakhraei²,

Niknam³

et al. 2019

CJN

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“…death of spouse, minor violations of law, neighbourhood socioeconomic status) have been studied in relation to depression [ 82 , 135 , 298 , 449 , 481 ]. A study reported an interaction of significant life events with functional variation in the serotonin-transporter-linked polymorphic region (5-HTTLPR) allele type (in the context of multiple sclerosis) and linked this to depression [ 361 ], while another reported an interaction between stress and 5-HTTLPR in relation to depression [ 480 ]. Other research reported that the genetic variation of HPA-axis genes has moderating effects on the relationship between stressors and depression [ 198 ].…”

Section: Cross-cutting Themesmentioning

confidence: 99%

Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature

2021

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Depression is one of the leading causes of disability, and, if left unmanaged, it can increase the risk for suicide. The evidence base on the determinants of depression is fragmented, which makes the interpretation of the results across studies difficult. The objective of this study is to conduct a thorough synthesis of the literature assessing the biological, psychological, and social determinants of depression in order to piece together the puzzle of the key factors that are related to this condition. Titles and abstracts published between 2017 and 2020 were identified in PubMed, as well as Medline, Scopus, and PsycInfo. Key words relating to biological, social, and psychological determinants as well as depression were applied to the databases, and the screening and data charting of the documents took place. We included 470 documents in this literature review. The findings showed that there are a plethora of risk and protective factors (relating to biological, psychological, and social determinants) that are related to depression; these determinants are interlinked and influence depression outcomes through a web of causation. In this paper, we describe and present the vast, fragmented, and complex literature related to this topic. This review may be used to guide practice, public health efforts, policy, and research related to mental health and, specifically, depression.

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“…The increased TAP aggression for S-allele carriers as compared to L-allele homozygotes is in line with the majority of literature suggesting an association with reactive aggression, although this is mainly shown in self-reported questionnaires and upon psychiatric evaluation ( Hallikainen et al, 1999 ; Cadoret et al, 2003 ; Gerra et al, 2005 ; Sakai et al, 2006 ; Gonda et al, 2009 ; Retz and Rösler, 2009 , but see Vassos et al, 2014 ). Interestingly, the short allele-variant of the 5-HTTLPR polymorphism has been associated with an increased risk to develop psychopathologies in combination with significant life events ( Caspi et al, 2003 ; Kenna et al, 2012 ; Aleknaviciute et al, 2018 ; Saul et al, 2018 ) and this association seems to depend on sex differences ( Du et al, 2000 ; Grabe et al, 2005 ; Sjöberg et al, 2006 ). Furthermore, a disrupted serotonin response has been associated with reactive aggression in particular ( Coccaro and Kavoussi, 1997 ) (see for reviews, Duke et al, 2013 ; Coccaro et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Threat-Avoidance Tendencies Moderate the Link Between Serotonin Transporter Genetic Variation and Reactive Aggression

Peeters

Lange

Borries

et al. 2020

Front. Behav. Neurosci.

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The short (S) allele of the serotonin transporter-linked promoter region (5-HTTLPR) polymorphism has been linked to reactive aggression in men, but this association is less consistent in females. Reactive aggression has been particularly described as a result of fear-driven defense to threat, but how this interaction between defensive behavior and aggression is expressed in S-allele carriers remains unknown. In order to explore this interplay between 5-HTTLPR genotype, defensive behavior and reactive aggression, we combined genotyping with objective measures of action tendencies toward angry faces in an approach-avoidance task (AAT) and reactive aggression in the Taylor aggression paradigm (TAP) in healthy females, N = 95. This study shows that female S-allele carriers in general display increased implicit reactive aggression (administering aversive white noise) toward opponents. Furthermore, we found that threat-avoidance tendencies moderate the association between 5-HTTLPR genotype and aggression displayed on the TAP. Together, these findings indicate a positive correlation between avoidance of angry faces in the AAT and reactive aggression in the TAP exclusively present in S-allele carriers.

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Polymorphism in the serotonin transporter gene polymorphisms (5-HTTLPR) modifies the association between significant life events and depression in people with multiple sclerosis

Cited by 5 publications

References 38 publications

Polymorphisms of serotonin transporter gene and psychological status in patients with multiple sclerosis

Polymorphisms of serotonin transporter gene and psychological status in patients with multiple sclerosis

Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature

Threat-Avoidance Tendencies Moderate the Link Between Serotonin Transporter Genetic Variation and Reactive Aggression

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