Serotonin Transporter Gene Promoter Polymorphism and Alexithymia

Kano, Michiko; Mizuno, Tomoko; Kawano, Yuko; Akiyama, Masashi; Kanazawa, Motoyori; Fukudo, Shin

doi:10.1159/000329554

Cited by 33 publications

(29 citation statements)

References 97 publications

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“…Furthermore, alexithymia contributes substantially to a greater rate of somatic IFN-related side effects in HCV patients [9]. This study aimed to replicate previous findings regarding the association between alexithymia and 5-HT-related gene polymorphisms [4,5] and, for the first time to our knowledge, to investigate longitudinally whether genetic factors (5-HTTLPR and HTR1A) and alexithymia may contribute to vulnerability to depression during IFN treatment in HCV patients.…”

Section: Introductionmentioning

confidence: 70%

“…This finding was partially unexpected because 5-HTTLPR-s is generally, though not unanimously, associated with negative emotionality [15]. However, in earlier studies this polymorphism was not associated with depression in HCV patients [7], and 5-HTTLPR-l was associated with alexithymia and independent from depressive symptoms [5]. Also, the higher prevalence of alexithymia in the 5-HTTLPR l/l carriers within our sample, though not as marked as with HTR1A, is similarly consistent with a reduced activation and decreased volume of the amygdala [14].…”

Section: Discussionmentioning

confidence: 99%

“…Laboratory studies have found possible candidate genes associated with alexithymia [3], particularly functional gene polymorphisms in the upstream regulatory region of the serotonin (5-HT) transporter coding sequence (5-HT-transporter-linked polymorphic region; 5-HTTLPR) and the 5-HT receptor (C-10119G of the HTR1A) [4,5]. Previous genetic investigations have recruited nonclinical subjects from general-population or convenience samples but, to our knowledge, no study has investigated clinical implications in terms of whether alexithymia interacts with 5-HT-related gene polymorphisms to increase the vulnerability to emotional distress.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Associations of Alexithymia in Predicting Interferon-Induced Depression in Chronic Hepatitis C

Porcelli

Cozzolongo

Cariola³

et al. 2015

Psychopathology

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Background: Previous studies have shown that alexithymia is associated with gene polymorphisms that regulate the availability of serotonin (5-HT) in the brain. Since the 5-HT network is involved in interferon (IFN)-induced depression, this paper aimed to investigate the role of alexithymia and the functional gene variants of the 5-HT1A receptor (HTR1A) and the 5-HT transporter (5-HTTLPR) in induction of depression during antiviral treatment. Methods: The depressive symptoms of 130 consecutive patients with chronic hepatitis C and no current psychopathology were measured during treatment with IFN and ribavirin (6-12 months) and at a 6-month follow-up. At baseline, alexithymia and 2 genotypes (5-HTTLPR and HTR1A) were also assessed. Results: Patients with homozygosity for HTR1A-G and 5-HTTLPR long alleles had significantly higher levels of alexithymia. After controlling for sociodemographic and disease-related factors, alexithymia and HTR1A-G polymorphism, both separately (20-22%) and jointly (14-16%), significantly and independently predicted the development of IFN-induced depression. Conclusions: Subjects carrying HTR1A-G and 5-HTTLRP double long alleles are more vulnerable to alexithymia. Also patients with a higher level of alexithymia and the HTR1A-G gene variant are more vulnerable to experiencing IFN-induced depressive symptoms. The clinical implications of targeting alexithymia and HTR1A receptors as a possible treatment option for mood disorders should be investigated in further studies.

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Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic Associations of Alexithymia in Predicting Interferon-Induced Depression in Chronic Hepatitis C

Porcelli

Cozzolongo

Cariola³

et al. 2015

Psychopathology

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“…Its psychological and neurobiological manifestations may be mediated by dysregulation of immune functions and proinflammatory cytokines, although the exact nature of this link is still unclear [17, 19, 22-24]. In addition, alexithymia is genetically influenced [25] and associated with genes that regulate the level of 5-HT in the brain, including the serotonin transporter 5-HTT [26]. The major role of 5-HTT is the removal of 5-HT from the synaptic cleft for recycling and metabolic decomposition.…”

Section: Introductionmentioning

confidence: 99%

“…The long allele (L) of the 5-HTT gene polymorphic region (5-HTTLPR) is more efficient in transcriptional activity and serotonin reuptake as compared to the short allele (S) and it is associated with reduced 5-HT neurotransmission [27]. Although the S allele is strongly implicated in the neuroanatomical structure of the brain and in disorders such as anxiety and depression [28-31], LL subjects appear to be more vulnerable to alexithymia than SL and SS subjects [26, 32]. In addition, the 2 functional allelic variants have been linked to a bias in the inflammatory response [33], thus pointing to the possible implication of genome-dependent 5-HTT activity in immune-mediated emotion regulation.…”

Section: Introductionmentioning

confidence: 99%

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study

Sacchinelli¹,

Piras²,

Orfei³

et al. 2018

Neuroimmunomodulation

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Objective: Interaction between the nervous and immune systems may influence emotions, ultimately affecting human health. Cytokines may play a role in developing emotional dysregulation as in alexithymia, a personality construct characterized by the subclinical inability to identify and describe emotions, often associated with several psychiatric and psychosomatic disorders. The proinflammatory cytokine IL-18, with a recognized role in brain functions, may influence serotonin metabolism and appears to be associated with alexithymia. Healthy individuals carrying the long allele (L) of the serotonin transporter gene polymorphic region (5-HTTLPR), and thus having lower concentrations of serotonin in the synaptic cleft, show a greater tendency toward alexithymia, with some gender differences. To explore a potential physiological interaction between IL-18, serotonin neurotransmission, and alexithymia, we investigated whether IL-18 serum levels and 5-HTTLPR are linked to alexithymic traits in healthy subjects. Methods: We measured IL-18 serum levels in 115 Italian-Caucasian healthy subjects genotyped for 5-HTTLPR allele variants, divided by gender and assessed for alexithymia scores using the 20-item Toronto Alexithymia Scale. Results: IL-18 levels are significantly more elevated in individuals with the LL genotype (n = 25) than in carriers of the short allele (n = 90, p = 0.0073). Specifically, in LL males (n = 11), i.e., the group with the most relevant increase in IL-18, cytokine values positively correlated with difficulty identifying feelings, which is a component of alexithymia (r = 0.634, p = 0.036). Conclusions: These results indicate a possible novel interaction between IL-18 and the serotoninergic system to mediate emotional unawareness, suggesting putative biological predictors of emotional dysregulation, which in turn can act as a risk factor for a variety of medical conditions in susceptible subjects.

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Insula’s functional connectivity with ventromedial prefrontal cortex mediates the impact of trait alexithymia on state tobacco craving

et al. 2013

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Rationale Alexithymia is a personality trait characterized by difficulty indentifying and describing subjective emotional experiences. Decreased aptitude in the perception, evaluation, and communication of affectively laden mental states has been associated with reduced emotion regulation, more severe drug craving in addicts, and structural/functional alterations in insula and anterior cingulate cortex (ACC). The insula and ACC represent sites of convergence between the putative neural substrates of alexithymia and those perpetuating cigarette smoking. Objectives We examined the interrelations between alexithymia, tobacco craving, and insula/ACC neurocircuitry using resting-state functional connectivity (rsFC). Methods Overnight-deprived smokers (n=24) and non-smokers (n=20) completed six neuroimaging assessments on different days both in the absence of, and following, varenicline and/or nicotine administration. In this secondary analysis of data from a larger study, we assessed trait alexithymia and state tobacco craving using self-reports and examined the rsFC of bilateral insular subregions (anterior, middle, posterior) and dorsal ACC. Results Higher alexithymia in smokers predicted reduced rsFC strength between the right anterior insula (aI) and ventromedial prefrontal cortex (vmPFC). Higher alexithymia also predicted more severe tobacco craving during nicotine withdrawal. Critically, the identified aI–vmPFC circuit fully mediated this alexithymia–craving relation. That is, elevated alexithymia predicted decreased aI–vmPFC rsFC and, in turn, decreased aI–vmPFC rsFC predicted increased craving during withdrawal. A moderated mediation analysis indicated that this aI–vmPFC mediational effect was not observed following drug administration. Conclusions These results suggest that a weakened right aI–vmPFC functional circuit confers increased liability for tobacco craving during smoking abstinence. Individual differences in alexithymia and/or aI–vmPFC functional coupling may be relevant factors for smoking cessation success.

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Serotonin Transporter Gene Promoter Polymorphism and Alexithymia

Cited by 33 publications

References 97 publications

Genetic Associations of Alexithymia in Predicting Interferon-Induced Depression in Chronic Hepatitis C

Genetic Associations of Alexithymia in Predicting Interferon-Induced Depression in Chronic Hepatitis C

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study

Insula’s functional connectivity with ventromedial prefrontal cortex mediates the impact of trait alexithymia on state tobacco craving

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