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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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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