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| 2. |
- Arranz, Belén
(författare)
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Neurobiological aspects of human aging and suicide
- 1994
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses: 1) The involvement of the monoaminergic and neuropeptidergic neurotransmitter systems in the aging process, and 2) The contribution of these systems in the etiology of an age-related mental disorder: the depressive syndrome. Because of the evidence suggesting the efficacy of the SSRI in the treatment of some age-related symptoms, a comparison study of the binding characteristics of two SSRI, i.e. [3H]paroxetine and [3H]citalopram, to the human brain 5-HT uptake site was included.Neurochemical analysis, involving HPLC, binding assays and RIA methods, was performed in several brain regions from 23 control subjects and 18 suicides pooled according to the method of death and the prior existence of depressive symptoms.Both [3H]paroxetine and [3H]citalopram were found to label the same number of presynaptic 5-HT binding sites, which is in accordance to their ability to identify the same membrane protein. However, the 15 to 30-fold higher affinity displayed by [3H]paroxetine gives evidence to this SSRI having a more easily accesible binding domain in the 5-HT transport complex than [3H]citalopram, and hence being a better marker of thispresynaptic 5-HT carrier system.No statistical differences in either the monoamines 5-HT, NA and DA, their metabolites or the 5-HT binding sites were found between controls and overall suicides. However, a diminished number of 5-HTl D binding sites with advancing age, together with a significant decrease in the number of 5-HTl D binding sites and binding affinity was noticed in the nondepressed and depressed suicides, respectively. These results might indicate the involvement of this novel 5-HT receptor in both some of the physical disturbances present in the elderly population and in the mechanisms underlying the depressive syndrome. Advancing age was also found to be negatively correlated with brain NA, DA and HV A concentrations, thus supporting the increased likelihood of changes in feeding habits and in the hypothalamic-mediated endocrine dysfunctionscommonly observed in senescence.With regard to the neuropeptidergic neurotransmitter systems, age-related decreases in gyrus cinguli NPY and CRF concentrations were noted. In addition, although unchanged NPY, SOM and CRF concentrations were observed in the overall suicide group, the HPLC analysis revealed that the depressed suicides showed a different pattern of NPY-LI fragments, which is in agreement with depression being associated with an altered processing or metabolism of the intact NPY molecule.
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- Holländare, Fredrik, 1972-
(författare)
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Managing depression via the Internet : self-report measures, treatment & relapse prevention
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cognitive behaviour therapy (CBT) is an effective treatment for depression but access is limited. One way of increasing access is to offer CBT via the Internet. In Study I, guided Internet-based CBT was found to have a large effect on depressive symptoms compared to taking part in an online discussion group. Approximately two hours were spent on guiding each patient and the large effect found differs from previous studies that showed smaller effects, probably due to lack of guidance. The intervention had no effect on the participants’ quality of life but significantly decreased their level of anxiety. Internet-based versions of self-report measures can be more practical and efficient than paper versions. However, before implementation, evidence of psychometrical equivalence to the paper versions should be available. This was tested in Studies II and III for the Montgomery-Åsberg Depression Rating Scale – Self-rated (MADRS-S) and the Beck Depression Inventory – Second Edition (BDI-II). When the full scales were investigated, equivalent psychometric properties were found in the two versions of the MADRS-S and BDI-II. However, in the Internet-version of the BDI-II, a lower score was found for the question about suicidality and the difference was statistically significant. Although the difference was small, this indicates that suicidality might be underestimated when using the Internet-based BDI-II. As the long-term prognosis after treatment for depression is poor, in Study IV we investigated the possibility of delivering CBT-based relapse prevention via the Internet. The results revealed that fewer participants in the intervention group experienced a relapse compared to the control group and that the time spent on guiding each participant was approximately 2.5 hours. A trend towards a higher remission rate was found in the CBT group at the six-month follow-up and a reduction of depressive symptoms was associated with a lowered risk of relapse. CBT-based relapse prevention via the Internet can potentially be made available to large numbers of patients, thus improving their prognosis. The Internet increases the possibilities for health care providers in the management of depression.
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- Humble, Mats B., 1952-
(författare)
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Obsessive-compulsive disorder, serotonin and oxytocin : treatment response and side effects
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obsessive-compulsive disorder (OCD), with a prevalence of 1-2 %, frequently leads a chronic course. Persons with OCD are often reluctant to seek help and, if they do, their OCD is often missed. This is unfortunate, since active treatment may substantially improve social function and quality of life. Serotonin reuptake inhibitors (SRIs) have welldocumented efficacy in OCD, but delayed response may be problematic. Methods to predict response have been lacking. Because SRIs are effective, pathophysiological research on OCD has focussed on serotonin. However, no clear aberrations of serotonin have been found, thus other mechanisms ought to be involved.Our aims were to facilitate clinical detection and assessment of OCD, to search for biochemical correlates of response and side-effects in SRI treatment of OCD and to identify any possible involvement of oxytocin in the pathophysiology of OCD.In study I, we tested in 402 psychiatric out-patients the psychometric properties of a concise rating scale, “Brief Obsessive Compulsive Scale” (BOCS). BOCS was shown to be easy to use and have excellent discriminant validity in relation to other common psychiatric diagnoses.Studies II-V were based on 36 OCD patients from a randomised controlled trial of paroxetine, clomipramine or placebo. In study II, contrary to expectation, we found that the change (decrease) of serotonin in whole blood was most pronounced in non-responders to SRI. This is likely to reflect inflammatory influence on platelet turnover rather than serotonergic processes within the central nervous system.In studies IV-V, we found relations between changes of oxytocin in plasma and the anti-obsessive response, and between oxytocin and the SRI related delay of orgasm, respectively. In both cases, the relation to central oxytocinergic mechanisms is unclear. In males, delayed orgasm predicted anti-obsessive response.
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- Iliadis, Stavros I, 1983-
(författare)
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Personality and the HPA-axis in Association with Postpartum Depression
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Postpartum depression is a psychiatric disorder affecting a substantial proportion of newly delivered women, and remains a significant cause of childbirth-related morbidity. The aim of the present thesis was to examine psychological, endocrine and genetic aspects of postpartum depression in a large, population-based sample of women in Uppsala, Sweden. All included studies were undertaken as parts of the BASIC-project, a longitudinal study on psychological wellbeing during pregnancy and the postpartum period. Study participants were screened for depressive symptoms in pregnancy week 17 and 32 as well as at six weeks and six months postpartum, mainly by use of the Swedish version of the Edinburgh Postnatal Depression Scale (EPDS). Furthermore, personality was assessed with the Swedish universities Scale of Personality (SSP) in pregnancy week 32. Evening cortisol levels in saliva were measured in pregnancy week 36 and at six weeks postpartum. Blood samples were obtained to measure corticotropin-releasing hormone levels (CRH) and to perform genetic analyses. The results of this thesis demonstrate that neuroticism is a strong and independent predictive factor of depressive symptoms at six weeks and six months postpartum, and has a significant mediatory role in the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1) and postpartum depression. Furthermore, women with postpartum depressive symptoms present with a dysregulated hypothalamic-pituitary-adrenal axis activity in terms of elevated cortisol levels postpartum, as well as elevated CRH levels in mid-gestation. In conclusion, this thesis develops current knowledge on several attributes of postpartum depression. Further studies are required to replicate and expand on these results, which would further contribute to early identification of women at risk of postpartum depression and adoption of proper interventions that may moderate the short- and long-term consequences of the disorder.
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| 7. |
- Lindqvist, Daniel, et al.
(författare)
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Increased Plasma Levels of Circulating Cell-Free Mitochondrial DNS in Suicide Attempters - Associations with HPA-Axis Hyperactivity
- 2017
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 81:10, s. S228-S228
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major Depressive Disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood, but no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample.Methods: In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and associated with hypothalamic pituitary adrenal (HPA)-axis hyperactivity. Results: Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared to healthy controls at different time points (pre- and post-DST) (all p-values ,2.98E-12, Cohen’s d ranging from 2.55-4.01). Pre-DST plasma levels of mtDNA were positively correlated with postDST cortisol levels (rho50.49, p,0.003).Conclusions: Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased freecirculating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.
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| 9. |
- Ågren, Hans, 1945, et al.
(författare)
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Psykiatrisk laboratorieutredning
- 2009
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Ingår i: Psykiatri. Eds Herlofsson, Ekselius, Lundh, Lundin, Mårtensson & Åsberg. - Lund : Studentlitteratur. - 9789144040264 ; , s. 149-52
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Åslund, Cecilia, 1977-
(författare)
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Depression and Antisocial Behaviour in Adolescents : Influence of Social Status, Shaming, and Gene-Environment Interaction
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigated (1) social status and shaming experiences in relation to aggressive behaviour and depression, and (2) gene-environment interactions between two genetic polymorphisms related to the serotonergic system – MAOA-VNTR and 5HTTLPR – and experiences of maltreatment in relation to delinquent behaviour and depression among adolescents. The four included studies are based on questionnaire data from the Survey of Adolescent Life in Vestmanland 2006 (SALVe-2006). A total of 5396 students in 9th (15-16 years old) grade of elementary school and 2nd (17-18 years old) grade of high school comprised the target population. The students in 2nd grade of high school also provided a saliva sample for gene extraction. There were strong associations between shaming experiences and both aggressive behaviour and depression. In addition, individuals who reported many shaming experiences and had either low or high social status had increased risks of physical aggression or depression, whereas medium social status seemed to have a protective effect. Gene-environment interactions were found between experiences of maltreatment and the MAOA-VNTR in relation to delinquent behaviour. Moreover, the direction of the gene-environment interaction differed depending on sex: boys with the short (S) variant of the MAOA-VNTR, in contrast to girls with the long (LL) variant, had the highest risk of delinquency in combination with maltreatment. Gene-environment interactions were also found between experiences of maltreatment and the 5HTTLPR in relation to depression among girls. The girls that were homozygous for the S allele (SS) had the highest risk of depression in combination with maltreatment. Among boys however, no gene-environment interaction was found between the 5HTTLPR and maltreatment in relation to depression. In conclusion, it is important to consider both genetic effects, and psychosocial factors such as social status, shaming experiences, and experiences of maltreatment when investigating different aspects of health and behaviour among adolescents.
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