Polymorphism of the serotonin transporter gene modulates brain and physiological responses to acute stress in Japanese men

Ohira, Hideki; Morikura, Masahiro; Isowa, Tokiko; Nomura, Michio; Ichikawa, Naho; Kimura, Kenta; Kanayama, Noriaki; Murakami, Hiroki; Osumi, Takahiro; Konagaya, Toshihiro; Nogimori, T; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro

doi:10.3109/10253890902787826

Cited by 15 publications

(19 citation statements)

References 65 publications

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“…Ohira et al . also reported that Japanese individuals with the s/s genotype of the 5-HTTLPR showed greater blood pressure reactivity to an acute stressor than those with the s/l or l/l genotype 6 . Taken together, it is speculated that s/s individuals in Japanese are prone to become depression by psychological stress.…”

Section: Discussionmentioning

confidence: 91%

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Voxel-based morphometric brain comparison between healthy subjects and major depressive disorder patients in Japanese with the s/s genotype of 5-HTTLPR

Igata

Kakeda

Watanabe

et al. 2017

Sci Rep

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Individuals with s/s genotype of serotonin transporter gene-linked promotor region (5-HTTLPR), which appear with a high frequency in Japanese, exhibit more diagnosable depression in relation to stressful life events than those with the s/l or l/l genotype. We prospectively investigated the brain volume changes in first-episode and medication naïve major depression disorder patients (MDD) with the s/s genotype in Japanese. We assessed the differences between 27 MDD with the s/s genotype and 44 healthy subjects (HS) with the same genotype using a whole-brain voxel-by-voxel statistical analysis of MRI. Gray matter volume in a brain region with significant clusters obtained via voxel-based morphometry analysis were measured and, as an exploratory analysis, evaluated for relationships to the subcategory scores (core, sleep, activity, psychic, somatic anxiety, delusion) of the Hamilton Depression Rating Scale (HAM-D) and the Social Readjustment Rating Scale (SRRS). The brain volume in the left insula lobe was significantly smaller in the MDD than in the HS. The left insula lobe volume correlated negatively with the “psychic” score of HAM-D and the SRRS. In a Japanese population with the s/s genotype, we found an atrophy of the insula in the MDD, which might be associated with “psychic” symptom and stress events.

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Section: Discussionmentioning

confidence: 91%

“…Many studies have suggested an association between the 5-HTT genotype and physiological reactivity to acute stressors 6, 7 . Gotlib et al .…”

Section: Introductionmentioning

confidence: 99%

Voxel-based morphometric brain comparison between healthy subjects and major depressive disorder patients in Japanese with the s/s genotype of 5-HTTLPR

Igata

Kakeda

Watanabe

et al. 2017

Sci Rep

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“…In recent years, a possible association of the 5-HTTLPR with youth depression has been traced in numerous studies [42-54]. Most studies were based on Caucasian populations, except for a few examining the Japanese general population [55,56]. No significant genotypic association of the 5-HTTLPR polymorphism with depression in a Japanese pediatric population, particularly in patients who have adverse parental environment, was operationalized as the mothers’ history of recurrent major depressive disorder.…”

Section: Discussionmentioning

confidence: 99%

No interaction between serotonin transporter gene (5-HTTLPR) polymorphism and adversity on depression among Japanese children and adolescents

et al. 2013

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BackgroundIdentification of gene × environment interactions (G × E) for depression is a crucial step in ascertaining the mechanisms underpinning the disorder. Earlier studies have indicated strong genetic influences and numerous environmental risk factors. In relation to childhood and adolescent depression, evidence is accumulating that the quality of the parental environment is associated with serotonin biology in children. We hypothesized that maternal depression is a crucial environmental risk factor associated with serotonin-regulating genes.MethodsThis study was designed to ascertain the G × E interaction for diagnosis of depression in a Japanese pediatric sample. DNA samples from 55 pediatric patients with depression and 58 healthy schoolchildren were genotyped for the 5-HTT (2 short (S) alleles at the 5-HTT locus) promoter serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphism. We examined whether an adverse parental environment, operationalized as the mother’s history of recurrent major depressive disorder, interacts with 5-HTTLPR polymorphism to predict patients’ depression symptoms.ResultsBinary logistic regression analyses revealed that maternal depression (adversity), gender, and FSIQ significantly affect the diagnosis of depression among children and adolescents. However, no main effect was found for adversity or genotype. Results of multivariable logistic regression analyses using stepwise procedure have elicited some models with a good fit index, which also suggests no interaction between 5-HTTLPR and adversity on depression.ConclusionsTo assess G × E interaction, data obtained from children and adolescents who had been carefully diagnosed categorically and data from age-matched controls were analyzed using logistic regression. Despite an equivocal interaction effect, adversity and gender showed significant main effects.

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“…Further, each immune measure showed a wide range of reactivity to school entry, variability in immune response that has now been broadly documented (e.g., (14, 21, 43, 45, 46)). Such differences are likely multi-factorial in origin and may be affected by gene polymorphisms (47, 48), experiences of social subordination (49), and coping styles (50). …”

Section: Discussionmentioning

confidence: 99%

Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

Thomas

Wara²,

Saxton³

et al. 2013

Psychosomatic Medicine

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Objective To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. Methods Data from 38 HIV+ and 29 HIV− children born to seropositive women were obtained before and after school entry. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity (based on mean arterial responses to challenge tasks), and enumerative and functional changes in peripheral blood immune parameters. Results In comparison to children who were HIV−, children who were HIV+ at baseline had fewer CD4+ T lymphocytes (M = 916 vs. 1206 cells/mm3 × 103; F = 7.8, p = .007), more CD8+ cells (M = 1046 vs. 720 cells/mm3 ×103; F = 7.98, p = .006), and diminished NK cell cytotoxicity (M =−.29 vs. .41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters following school entry were associated with family stress and pre school entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8+ cells following school entry or the greatest decrease, depending upon reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. Conclusions These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV.

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Polymorphism of the serotonin transporter gene modulates brain and physiological responses to acute stress in Japanese men

Cited by 15 publications

References 65 publications

Voxel-based morphometric brain comparison between healthy subjects and major depressive disorder patients in Japanese with the s/s genotype of 5-HTTLPR

Voxel-based morphometric brain comparison between healthy subjects and major depressive disorder patients in Japanese with the s/s genotype of 5-HTTLPR

No interaction between serotonin transporter gene (5-HTTLPR) polymorphism and adversity on depression among Japanese children and adolescents

Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

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