| 1. |
- Bendre, Megha, et al.
(författare)
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Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats.
- 2019
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Ingår i: Alcohol. - : Elsevier BV. - 0741-8329 .- 1873-6823. ; 79, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. The monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next-generation bisulfite sequencing of the Maoa promoter, intron 1-5, exons 5 and 6, together comprised of 107 CpGs, in a subgroup of rats. Pyrosequencing was used to analyse the methylation of ten candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interaction effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption and Maoa expression in reward-related brain regions.
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| 2. |
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| 3. |
- Comasco, Erika, 1982-, et al.
(författare)
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Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression
- 2019
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 10:7, s. 3132-3142
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Tidskriftsartikel (refereegranskat)abstract
- Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt± and 5-htt+/+ male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt+/+ rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt+/− genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not across, brain regions in all groups except in non-maternally separated 5-htt+/+ rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents.
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| 4. |
- Granholm, Linnea, et al.
(författare)
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Episodic Ethanol Exposure in Adolescent Rats Causes Residual Alterations in Endogenous Opioid Peptides
- 2018
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Ingår i: Frontiers in Psychiatry. - : FRONTIERS MEDIA SA. - 1664-0640. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Adolescent binge drinking is associated with an increased risk of substance use disorder, but how ethanol affects the central levels of endogenous opioid peptides is still not thoroughly investigated. The aim of this study was to examine the effect of repeated episodic ethanol exposure during adolescence on the tissue levels of three different endogenous opioid peptides in rats. OutbredWistar rats received orogastric (i.e., gavage) ethanol for three consecutive days per week between 4 and 9 weeks of age. At 2 h and 3 weeks, respectively, after the last exposure, beta-endorphin, dynorphin B and Met-enkephalin-Arg(6)Phe(7) (MEAP) were analyzed with radioimmunoassay. Beta-endorphin levels were low in the nucleus accumbens during ethanol intoxication. Remaining effects of adolescent ethanol exposure were found especially for MEAP, with low levels in the amygdala, and high in the substantia nigra and ventral tegmental area three weeks after the last exposure. In the hypothalamus and pituitary, the effects of ethanol on beta-endorphin were dependent on time from the last exposure. An interaction effect was also found in the accumbal levels of MEAP and nigral dynorphin B. These results demonstrate that repeated episodic exposure to ethanol during adolescence affected opioid peptide levels in regions involved in reward and reinforcement as well as stress response. These alterations in opioid networks after adolescent ethanol exposure could explain, in part, the increased risk for high ethanol consumption later in life.
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| 5. |
- Granholm, Linnea, 1986-
(författare)
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Stress, Drugs and Neuroscience : Neurobiological Effects of Social Stressors and Drug Exposure in Young and Adolescent Rats
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Experiences early in life or during adolescence modulate neuronal networks in the immature brain and consequently lay the foundation for future susceptibility or resilience towards psychiatric disorders. The objective in this thesis is to understand, in part, how the surrounding environment shapes the brain of a young individual. Three types of negative life events were studied, in an animal model, for their effects on the brain reward system (i.e., endogenous opioids and dopamine) and voluntary drug intake. These were: disruption of maternal care, disruption of interaction with peers, and exposure to drugs. Stress, in the form of maternal separation, altered expression of opioid genes in the dorsal striatum and amygdala, and the response to subsequent alcohol intake on these genes was dependent on early life conditions. Basal levels of endogenous opioids were also dependent on how the animals were housed in early adolescence. Short single housing (30 minutes) caused an acute stress response as evidenced by increased serum corticosterone and nociceptin/orphanin FQ in brain areas associated with stress. A prolonged single housing resulted in a marked decrease of Met-Enk-Arg6-Phe7 (i.e., a marker of enkephalins) in several brain areas. The endogenous opioids were also affected by repeated exposure of ethanol during adolescence; ethanol intoxication increased the accumbal levels of Met-Enk-Arg6-Phe7 and decreased those of β-endorphin. Residual effects of the adolescent ethanol exposure were found in Met-Enk-Arg6-Phe7 levels in the amygdala, ventral tegmental area, and substantia nigra. Furthermore, rats exposed to ethanol as adolescents had alterations in the dopamine dynamics in the dorsal striatum. Both endogenous opioids and dopamine are essential in mediating rewarding properties. Alterations of these systems, caused by environmental disturbances and alcohol exposure, presented herein could explain, in part, the increased susceptibility for alcohol- and substance use disorders later in life.
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| 6. |
- Granholm, Linnea, et al.
(författare)
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The expression of opioid genes in non-classical reward areas depends on early life conditions and ethanol intake
- 2017
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1668, s. 36-45
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Tidskriftsartikel (refereegranskat)abstract
- The young brain is highly sensitive to environmental influences that can cause long-term changes in neuronal function, possibly through altered gene expression. The endogenous opioid system continues to mature after birth and because of its involvement in reward, an inadequate maturation of this system could lead to enhanced susceptibility for alcohol use disorder. Recent studies show that the classical reward areas nucleus accumbens and ventral tegmental area are less affected by early life stress whereas endogenous opioids in non-classical areas, e.g. dorsal striatum and amygdala, are highly responsive. The aim was to investigate the interaction between early life conditions and adult voluntary ethanol intake on opioid gene expression. Male Wistar rats were exposed to conventional rearing, 15, or 360min of daily maternal separation (MS) postnatal day 1-21, and randomly assigned to ethanol or water drinking postnatal week 10-16. Rats exposed to early life stress (MS360) had increased opioid receptor gene (Oprm1, Oprd1 and Oprk1) expression in the dorsal striatum. Ethanol drinking was associated with lower striatal Oprd1 and Oprk1 expression solely in rats exposed to early life stress. Furthermore, rats exposed to early life stress had high inherent Pomc expression in the amygdala but low expression after ethanol intake. Thus, adverse events early in life induced changes in opioid gene expression and also influenced the central molecular response to ethanol intake. These long-term consequences of early life stress can contribute to the enhanced risk for excessive ethanol intake and alcohol use disorder seen after exposure to childhood adversity.
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| 7. |
- Lager, Susanne, et al.
(författare)
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Alcohol consumption habits and associations with anxiety or depressive symptoms postpartum in women with high socioeconomic status in Sweden.
- 2022
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Ingår i: Archives of Women's Mental Health. - : Springer Nature. - 1434-1816 .- 1435-1102.
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Tidskriftsartikel (refereegranskat)abstract
- Postpar tum depression and anxiety are common among new mothers. It is well-established that in the general population alcohol use is associated with depression and anxiety. Linking alcohol consumption to symptoms of postpartum depression (PPDS) or postpartum anxiety (PPAS) is presently less established. This study aims to determine if alcohol consumption pre-pregnancy, 6 weeks postpartum, 6 months postpartum, or changes in alcohol consumption are associated with PPDS or PPAS. Longitudinal data on 3849 women from a Swedish perinatal cohort were analyzed using logistic regression analyses for associations between alcohol consumption and symptoms of anxiety or depression, as assessed with the Edinburgh Postnatal Depression Scale. There was no association between pre-pregnancy drinking habits and PPDS (p = 0.588, n = 2479) or PPAS (p = 0.942; n = 2449) at 6 weeks postpartum. Similarly, no associations were observed between concurrent drinking habits at 6 weeks postpartum and PPAS (p = 0.070, n = 3626), 6 months postpartum and PPDS (0.647, n = 3461) or PPAS (p = 0.700, n = 3431). However, there was an association between drinking habits at 6 weeks postpartum and concurrent PPDS (p = 0.047, n = 3659). In conclusion, robust associations were not found between postpartum alcohol consumption and mood symptoms. This lack of association between poor mental health and risk behaviors in new mothers could be interpreted as a result of long-term policy work and high participation in Swedish maternity care. Future studies need to address these research questions in more diverse socio-cultural contexts.
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| 8. |
- Landgren, Ellen, et al.
(författare)
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“Mastering a New Life Situation” – Patients’ Preferences of Treatment Outcomes in Early Rheumatoid Arthritis – A Longitudinal Qualitative Study
- 2020
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Ingår i: Patient Preference and Adherence. - : Dove Medical Press Ltd.. - 1177-889X. ; 14, s. 1421-1433
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore patients’ preferred treatment outcomes during their first two years with rheumatoid arthritis (RA). Patients and Methods: A qualitative, longitudinal, multicenter study with interviews at two time points was performed in Sweden. Individual interviews were conducted at time point 1 with 31 patients with RA, defined as disease duration of ≤1 year and treatment for 3–7 months. Seven focus group interviews and five individual interviews were conducted at time point 2 with 22 patients 12–20 months after treatment initiation. The interviews were analyzed using the Qualitative Analysis Guide of Leuven. A core category with four related concepts emerged. Results: The core finding of patient-preferred treatment outcomes was “mastering a new life situation”. Patients preferred to experience control of the disease by controlling the symptoms and by experiencing absence of disease. To experience autonomy by regaining former activity level, experiencing independence, and being empowered was another preferred outcome. Patients preferred to regain identity through being able to participate, experience well-being, and regain former self-image. To experience joy in everyday life through vitality and believing in the future was another preferred outcome. Patients’ preferences developed over time from the acute phase of controlling the symptoms and wanting to return to the life they lived prior to diagnosis, to a more preventive way of self-management and empower-ment to master the new life situation. Conclusion: The patients’ preferred treatment outcomes during the first two years with RA were to master their new life situation and changed from a preference to return to a life lived prior disease onset, to a preference of living with quality of life, despite RA. This study increases the understanding of patients’ preferred treatment outcomes in the early disease course and can be a foundation for tailoring interventions to be more person-centered and to improve long-term treatment outcomes. © 2020 Landgren et al.
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| 9. |
- Landgren, E., et al.
(författare)
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Patients' Perceptions of Person-Centred Care in Early RA : A Qualitative Study
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:Suppl. 1, s. 1024-1024
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Tidskriftsartikel (refereegranskat)abstract
- Data on patients’ experience can identify strengths and weaknesses with given care, why a person-centred care will improve health care quality. In rheumatology care, most research on patient preferences for and experiences of RA care is performed in patients with established RA and less often in patients with early RA. In the early course of RA patients often struggle to manage their new life situation with a chronic disease and its treatment. Expectations and experiences of health care may change over time why it is important to understand how newly diagnosed patients perceive person-centred care.Objectives:To explore patients’ perceptions of person-centred care early in the RA disease course within the framework of person-centred care.Methods:In this qualitative study 31 patients with early RA from four rheumatology specialist outpatient clinics were interviewed. An abductive qualitative content analysis was conducted based on the framework of McCormack and McCance (2006, 2016). The four constructs; prerequisites, care environment, person-centred processes, and person-centred outcomes constituted the four categories in the deductive part of the study. An inductive analysis revealed eleven sub-categories exploring the content of person-centred care for patients with early RA.Results:For patients with early RA person-centred care was described as; 1. Prerequisites were to be treated with respect, to meet dedicated healthcare professionals, and to meet professional competence. 2. The care environment was to have access to a multidisciplinary team, to have access to health care, and a supportive organization. 3. Person-centred processes were to be listened to, to be supported, and to be involved in decision-making. 4. The person-centred outcomes were to be satisfied with received health care and to achieve optimal health.Conclusion:A true person-centred care is important to patients early in the RA disease course, supporting the relevance to implement person-centred approach at all stages in the health care system. This study contributes to information about how to further develop person-centredness in rheumatology care also early in the disease course.References:[1]McCormack, B., & McCance, T. V. (2006). Development of a framework for person-centred nursing. J Adv Nurs, 56(5), 472-479. doi:10.1111/j.1365-2648.2006.04042.x[2]McCormack, B., & McCance, T. V. (2016). Person-centred practice in nursing and health care: theory and practice (2nd edition ed.): John Wiley & Sons.Disclosure of Interests:None declared
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| 10. |
- Landgren, Ellen, et al.
(författare)
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Patients’ Perceptions of Person‐Centered Care in Early Rheumatoid Arthritis : A Qualitative Study
- 2021
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Ingår i: ACR Open Rheumatology. - Hoboken, NJ : John Wiley & Sons. - 2578-5745. ; 3:11, s. 788-795
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Most research on patient experiences of rheumatoid arthritis (RA) care is performed with patients who have established RA and less often with patients with early RA. Experiences of and expectations about health care may change over time, which is why the aim was to explore patients’ perceptions of person-centered care (PCC) early in the RA disease course.Methods: Thirty-one patients with early RA were interviewed in this qualitative study. An abductive qualitative content analysis was conducted based on the framework of McCormack and McCance (1,2). The four constructs, prerequisites, care environment, person-centered processes, and person-centered outcomes, constituted the four categories in the deductive part of the study. An inductive analysis generated 11 subcategories exploring the content of PCC.Results: For patients with early RA, PCC was described in terms of 1) prerequisites including being treated with respect, meeting dedicated health care professionals, and meeting professional competence; 2) care environment including having access to a multidisciplinary team, having access to health care, and encountering a supportive organization; 3) person-centered processes including being listened to, being supported, and being involved in decision-making; and 4) person-centered outcomes including being satisfied with received health care and achieving optimal health.Conclusion: Genuine PCC is important for patients early in the RA disease course, supporting the implementation of a person-centered approach during all stages in the health care system. This study contributes to information about how to further develop person-centeredness in rheumatology care. © 2021 The Authors.
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