1. |
- Torres Soler, Catalina, et al.
(författare)
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Exploration of the Moderating Effects of Physical Activity and Early Life Stress on the Relation between Brain-Derived Neurotrophic Factor (BDNF) rs6265 Variants and Depressive Symptoms among Adolescents
- 2022
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Depression affects one in five persons at 18 years of age. Allele A of the brain-derived neurotrophic factor (BDNF) rs6265 is considered to be a risk factor for depression. Previous studies of the interaction between BDNF rs6265, early adversity, and/or physical activity have shown mixed results. In this study, we explored the relation between BDNF rs6265 polymorphism and childhood stress, as well as the moderating effect of physical activity in relation to depressive symptoms using binary logistic regressions and process models 1, 2 and 3 applied to data obtained at three times (waves 1, 2 and 3) from the Survey of Adolescent Life in Vastmanland cohort study (SALVe). Results revealed that both childhood stress and physical activity had a moderation effect; physical activity in wave 1 with an R-2 change = 0.006, p = 0.013, and the Johnson-Neyman regions of significance (RoS) below 1.259, p = 0.05 for 11.97%; childhood stress in wave 2 with the R-2 change = 0.008, p = 0 002, and RoS below 1.561 with 26.71% and >4.515 with 18.20%; and a three-way interaction in wave 1 in genotype AA carriers. These results suggest that allele A is susceptible to physical activity (positive environment) and childhood stress (negative environment).
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2. |
- Kanders, Sofia H., et al.
(författare)
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A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants
- 2020
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Ingår i: Drug development research. - : John Wiley & Sons. - 0272-4391 .- 1098-2299. ; 81:1, s. 102-113
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Tidskriftsartikel (refereegranskat)abstract
- The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population‐based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES‐D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES‐D score, occurrence of a major depressive episode (MDE) during follow‐up and regular antidepressant treatment during the 6 months preceding follow‐up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES‐D score (p = .001). The HTR1A rs878567 variant was associated with ln CES‐D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19 ) CC homozygotes showed a six‐fold higher likelihood of regular AD therapy at follow‐up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.
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3. |
- Kanders, Sofia H., et al.
(författare)
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Body mass index and bullying victimization as antecedents for depressive symptoms in a Swedish youth cohort
- 2022
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Ingår i: Journal of Public Health. - : Springer Nature. - 2198-1833 .- 1613-2238. ; 30:10, s. 2513-2524
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Tidskriftsartikel (refereegranskat)abstract
- AimThe bidirectional association between obesity and depression seen in adults is not clearly established in adolescents. The aim of this study was to investigate the longitudinal association between body mass index (BMI), depressive symptoms and interactions between bullying victimization and BMI, taking gender differences into account.Subjects and methodsIn a Swedish county, self-reported bullying victimization, BMI and depressive symptoms from 1729 adolescents (y = 14.4, 56% females) were collected in 2012 (wave 1), in 2015 (wave 2) (y = 17.3 ) and in 2018 (wave 3) (y = 19.9). Longitudinal associations were assessed using binary logistic regression models controlling for confounding factors. Interaction effects between BMI and victimization on depressive symptoms were also assessed.ResultsWave 1 obese males had approximately six times increased odds ratio compared to normal weight, for wave 2 depressive symptoms. W1 overweight was associated with an odds ratio of 1.5 in all participants for wave 3 depressive symptoms. Victimization was consistently associated with higher odds ratio for future depressive symptoms. We found interaction effects between bullying victimization and BMI for future depressive symptoms with different patterns depending on sex.Conclusion Given the present findings, bullying needs to be prevented, and, if it occurs, it needs to be stopped at an early stage toprevent future depressive symptoms.
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4. |
- Kanders, Sofia H., et al.
(författare)
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Breastfeeding moderates the relationship between fat mass and obesity-associated gene rs9939609 and body mass index among adolescents
- 2021
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Ingår i: Obesity Science & Practice. - : John Wiley & Sons. - 2055-2238. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Breastfeeding, which is important for early growth, is a possible moderator of genetic influence, such as the effect of the fat mass and obesity-associated gene (FTO) on body mass index (BMI). The aim of this study was to assess the moderating effect of breastfeeding duration on the relationship between FTO rs9939609 and BMI in a Caucasian sample.Methods Adolescents born in 1997 and in 1999, who were living in the Swedish county Västmanland in 2012, were invited to participate in the Survey of Adolescent Life in Västmanland. The adolescents and their parents completed self-reported questionnaires in 2012, 2015, and 2018. Genotyping of rs9939609 T > A polymorphism was conducted from saliva DNA samples. Interaction effects of parental reported breastfeeding duration in months, including regions of significance, on the relationship between rs9939609 and BMI plus overweight were assessed.Results Considering physical activity levels, parental reported breastfeeding duration was a moderator of the relationship between rs9939609 and BMI for the younger (regions of significance = <1.6 and >28.1 months) and older adolescents (region of significance = >19.9 months), but not for the young adults. Plots of the association between breastfeeding duration and BMI showed higher BMI for AA with short breastfeeding, but lower BMI with longer breastfeeding than AT and TT. Longer breastfeeding lowered the odds for overweight among the younger adolescents, especially among AA individuals.Conclusion Rs9939609 AA individuals were more susceptible than AT and TT individuals to both short and long breastfeeding durations, which is consistent with the differential susceptibility hypothesis. FTO rs9939609 AA might be a plasticity variant with differential susceptibility to environmental influences. Breastfeeding duration may be one of many factors that affect the relationship between rs9939609 and BMI.
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5. |
- Kanders, Sofia H.
(författare)
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The relationship between overweight and depression in view of genes, environment and their joint influence
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity and depression are known to often go hand in hand, but is this due to our genetic heritage, environmental factors or a combination thereof? With a neuroscientific approach, I have investigated the relationship between obesity and depression with the aim of bridging the different levels of research available in order to better understand this complex topic. Using data from a longitudinal cohort with adults, we analysed the genetic contribution to antidepressant response in Study I. The association between antidepressant treatment and changes in body mass index, waist circumference and fat mass was assessed in Study II. In Study III, the importance of bullying victimization for the relationship between obesity and depression was analysed using a longitudinal cohort with adolescents. Lastly, the moderating effect from breastfeeding duration on the relation between a known obesity associated gene and body mass index among adolescents and young adults was examined in Study IV.The bidirectional relationship between obesity and depression is derived from several joint processes and mechanisms such as the stress system and symptomatology overlap with strong environmental influences affecting both disorders, plausibly through epigenetic processes. Even though overweight and obesity were associated with depressive symptoms, one even more important environmental factor for the development of symptoms was bullying victimization – a risk factor that persisted after six years of follow-up. The genetic contribution to these complex disorders from individual variations is small in most cases, but with a credible additive effect and with environmental factors as important moderators of these relationships. One such moderator is breastfeeding duration, which was found to contribute to the relationship between FTO and future BMI with different patterns for the individual variants, which supports the differential susceptibility hypothesis. Finally, when AD treatment is used, the patient should be monitored regularly, both regarding depressive symptoms as well as obesity-related measurements.Overall, it is of high importance to focus on prevention because the frequently chronic course of obesity, as well as depression, has a high burden on individuals, as well as on society.
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7. |
- Torres Soler, Catalina, et al.
(författare)
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A Three-Way Interaction of Sex, PER2 rs56013859 Polymorphism, and Family Maltreatment in Depressive Symptoms in Adolescents
- 2023
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of depressive symptoms in adolescents is 12–18% and is twice as frequent in females. Sleep problems and thoughts of death are depressive symptoms or co-occurrent phenomena. Family maltreatment is a risk factor for later depressive symptoms and the period circadian regulator (PER) has been studied in relation to neurotransmitters, adaptation to stress, and winter depression. The purpose of this work was to study the relation of the three-way interactions of sex, PER2 rs56013859, and family maltreatment in relation to core depressive symptoms, sleep complaints, and thoughts of death and suicide in self-reports from a cohort of Swedish adolescents in 2012, 2015, and 2018. Cross-sectional and longitudinal analyses with linear and logistic regressions were used to study the relationships to the three outcomes. The three-way interaction was related to core depressive symptoms at both baseline and six years later. In contrast, the model did not show any relation to the other dependent variables. At 13–15 years, a sex-related differential expression was observed: females with the minor allele C:C/C:T exposed to family maltreatment showed higher levels of core depressive symptoms. Six years later, the trend was inverted among carriers of minor alleles.
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8. |
- Torres Soler, Catalina
(författare)
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Depression among Adolescents : Measurement and diagnosis, Environmental factors, and Genetics
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Depression is a common disorder and a major cause of disability. The prevalence of depression in adolescents is 12-25%. The use of valid instruments in psychiatric assessment contributes to diagnostic validity and consistency.This thesis is divided into four parts:The first and second parts study the psychometric properties of the MADRS-P and CSDS/CSDSP scales. The scales are adapted to measure symptoms and function in adolescents. In the first part, the psychometric properties of the Montgomery-Åsberg Depression Rating Scale Parent used for the assessment of parent-reported depressive symptoms in adolescents are studied. In the second part, the properties of the Swedish Child Sheehan Disability Scales, in the adolescent and parent versions, are studied. These scales are used to assess levels of function in school, relationships with friends and relationships with family. The properties of the scales were studied in a population of adolescents referred to the child and adolescent psychiatric clinic.The third study analyses the interaction between BDNF rs6265 polymorphism, childhood stress and physical activity in relation to depressive symptoms, showing that the interaction of BDNF rs6265 with childhood stress and physical activity is significant in moderation models. For A allele carriers, physical activity reduces depressive symptoms in youth exposed to childhood stress. In turn, exposure to a higher level of stress increases depressive symptoms in adolescents aged 13 and 15. The minor allele confers plasticity characteristics when interacting with the mentioned environmental factors.The fourth study shows that the interaction of the three factors PER2 rs56013859, sex and family maltreatment in relation to depressive symptoms is significant in female minor C allele carriers aged 13 and 15 years.The results obtained in this thesis are applicable in the practice of child and adolescent psychiatry, and in the prevention of depressive disorders in the child and adolescent population.
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