| 1. |
- Aiff, Harald, et al.
(författare)
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Effects of 10 to 30 years of lithium treatment on kidney function
- 2015
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 29:5, s. 608-614
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Tidskriftsartikel (refereegranskat)abstract
- Long-term lithium treatment is associated with end-stage renal disease, but there is little evidence of a clinically significant reduction in renal function in most patients. We previously found that 1.5% of people who took lithium from the 1960s and 1970s developed end-stage renal disease; however, none of the patients who started after 1980 had end-stage renal disease. Here we aimed to study the prevalence and extent of kidney damage during the course of long-term lithium treatment since 1980. We retrieved serum lithium and creatinine levels from 4879 patients examined between 1 January 1981 and 31 December 2010. Only patients who started their lithium treatment during the study period and had at least 10 years of cumulative treatment were included. The study group comprised 630 adult patients (402 women and 228 men) with normal creatinine levels at the start of lithium treatment. There was a yearly increase in median serum creatinine levels already from the first year of treatment. About one-third of the patients who had taken lithium for 10-29 years had evidence of chronic renal failure but only 5% were in the severe or very severe category. The results indicate that a substantial proportion of adult patients who are treated with lithium for more than a decade develop signs of renal functional impairment, also when treated according to modern therapeutic principles. Our results emphasise that lithium treatment requires continuous monitoring of kidney function.
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| 2. |
- Di Bonaventura, MVM, et al.
(författare)
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Regulation of adenosine A2A receptor gene expression in a model of binge eating in the amygdaloid complex of female rats
- 2019
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 33:12, s. 1550-1561
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited.Methods and aims:Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2AAdenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes.Results:Gene expression analysis revealed a selective increase of both receptor mRNAs in the amygdaloid complex of stressed and restricted rats, which exhibited binge-like eating, when compared to non-stressed and non-restricted rats. Consistently, pyrosequencing analysis revealed a significant reduction of the percentage of DNA methylation but only at the A2AAR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A2AAR agonist (VT 7) administration (which inhibited the episode of binge systemically at 0.1 mg/kg or intra-central amygdala (CeA) injection at 900 ng/side) induced a significant increase of A2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2AAR mRNA levels in rats treated with the A2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94.Conclusion:We confirm the role of A2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.
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| 3. |
- Evers, Simon S., et al.
(författare)
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Roman high and low avoidance rats differ in their response to chronic olanzapine treatment at the level of body weight regulation, glucose homeostasis, and cortico-mesolimbic gene expression
- 2017
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 31:11, s. 1437-1452
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Tidskriftsartikel (refereegranskat)abstract
- Olanzapine, an antipsychotic agent mainly used for treating schizophrenia, is frequently associated with body weight gain and diabetes mellitus. Nonetheless, studies have shown that not every individual is equally susceptible to olanzapine's weight-gaining effect. Therefore, Roman high and low avoidance rat strains were examined on their responsiveness to olanzapine treatment. The Roman high avoidance rat shares many behavioral and physiological characteristics with human schizophrenia, such as increased central dopaminergic sensitivity, whereas the Roman low avoidance rat has been shown to be prone to diet-induced obesity and insulin resistance. The data revealed that only the Roman high avoidance rats are susceptible to olanzapine-induced weight gain and attenuated glucose tolerance. Here it is suggested that the specific olanzapine-induced weight gain in Roman high avoidance rats could be related to augmented dopaminergic sensitivity at baseline through increased expression of prefrontal cortex dopamine receptor D1 mRNA and nucleus accumbens dopamine receptor D2 mRNA expression. Regression analyses revealed that olanzapine-induced weight gain in the Roman high avoidance rat is above all related to increased prolactin levels, whereas changes in glucose homeostasis is best explained by differences in central dopaminergic receptor expressions between strains and treatment. Our data indicates that individual differences in dopaminergic receptor expression in the cortico-mesolimbic system are related to susceptibility to olanzapine-induced weight gain.
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| 4. |
- Furmark, Tomas, et al.
(författare)
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Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder
- 2016
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Ingår i: Journal of Psychopharmacology. - London, United Kingdom : SAGE Publications. - 0269-8811 .- 1461-7285. ; 30:10, s. 1028-1035
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Tidskriftsartikel (refereegranskat)abstract
- It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[ -C-11]tryptophan, [C-11]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [C-11]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.
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| 5. |
- Golic, M., et al.
(författare)
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Compliance with the safety guidelines for long-term lithium treatment in Sweden
- 2018
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 32:10, s. 1104-1109
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lithium has been used for more than 50 years and guidelines for treatment monitoring have been documented in Sweden since the beginning of the 1980s. Aims: The aim of this study was to describe compliance over time with the Swedish guidelines for long-term lithium treatment. Methods: The study material was obtained from Sahlgrenska University Hospital's laboratory database. We analysed data (serum lithium and serum creatinine) of adult patients treated with lithium between 1981 and 2010, and determined compliance with guidelines and serum lithium levels over time. Results: Our study material included 2841 patients and 25,300 treatment-years. The compliance with guidelines' recommendations regarding lithium and creatinine monitoring increased from 36% in 1981 to 68% in 2010. Women were on average 2% more compliant than men (p < 0.01). Most lithium samples (87-94%) were within recommended intervals throughout the study period. The average lithium level decreased from 0.70 mmol/L in 1981 to 0.58 mmol/L in 2001, and remained stable thereafter. Conclusions: Compliance with lithium monitoring guidelines improved slowly but steadily over time. It took three decades to reach a compliance rate of just below 70%. Gender differences were small, but with a significantly better compliance rate for women. Serum lithium was kept within the recommended target interval to a large extent, throughout the study period.
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| 6. |
- Goodwin, G. M., et al.
(författare)
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Evidence-based guidelines for treating bipolar disorder : Revised third edition recommendations from the British Association for Psychopharmacology
- 2016
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Ingår i: Journal of Psychopharmacology. - : SAGE PUBLICATIONS LTD. - 0269-8811 .- 1461-7285. ; 30:6, s. 495-553
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Forskningsöversikt (refereegranskat)abstract
- The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
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| 7. |
- Hayes, JF, et al.
(författare)
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Psychiatric hospitalization following antipsychotic medication cessation in first episode psychosis
- 2019
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 33:4, s. 532-534
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Tidskriftsartikel (refereegranskat)abstract
- There are questions about the risk-benefit balance of longer-term antipsychotic medication treatment following first episode psychosis, especially in relation to relapse because of dopamine supersensitivity following treatment cessation. Aim: The purpose of this study was to determine whether hospitalization rates in first episode psychosis patients are associated with length of initial oral antipsychotic medication exposure. Methods: We examined psychiatric hospitalization rates in patients experiencing first episode of psychosis from the total population of Sweden between 1 January 2007–31 December 2016 ( n=7043). We categorised patients by the length of first antipsychotic treatment (<6 months, 6 months to <1 year, 1 year to <2 years, 2 years to <5 years and ⩾5 years). Results: Compared to those treated for <6 months, individuals receiving oral antipsychotic medications for ⩾5 years had less than half the cumulative incidence of hospitalization at all times between 1–4 years after treatment cessation. Conclusion: We found no evidence that hospitalization rates increased with increasing baseline antipsychotic exposure.
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| 8. |
- Hjorth, Stephan, 1953
(författare)
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Looking back (and in)to the future: A personal reflection on 'Serotonin autoreceptor function and antidepressant drug action' (Hjorth et al.2000)
- 2016
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 30:11, s. 1129-1136
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Tidskriftsartikel (refereegranskat)abstract
- Our article in this journal some 15 years ago focussed on the role of serotonin (5-HT) autoreceptors in the mechanism of action of antidepressant drugs. Specifically in this regard, the results were summarised of rat microdialysis studies carried out to examine: (a) the relative importance of 5-HT1A and 5-HT1B autoreceptors, including (b) possible regional variation, and (c) potential changes in autoreceptor responsiveness following chronic selective serotonin reuptake inhibitor administration. In the present reflection piece, I recap some of the key findings against a brief background and provide an account of their bearing within the context of subsequent endeavours in the antidepressant drug research and development field. I conclude by shortly commenting on selected topics relevant to novel, interesting advances and avenues for future research. © The Author(s) 2016.
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| 9. |
- Millon, C, et al.
(författare)
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Role of the galanin N-terminal fragment (1-15) in anhedonia: Involvement of the dopaminergic mesolimbic system
- 2019
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 33:6, s. 737-747
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Tidskriftsartikel (refereegranskat)abstract
- Anhedonia is a core feature of depressive disorders. The galanin N-terminal fragment (1-15) plays a role in mood regulation since it induces depression and anxiogenic-like effects in rats. In this study, we analysed galanin N-terminal fragment (1-15) actions in anhedonic-like behaviours in rats using operant and non-operant tests and the areas involved with these effects. Methods: Galanin N-terminal fragment (1-15) effects were analysed in saccharin self-administration, sucrose preference, novelty-suppressed feeding and female urine sniffing tests. The areas involved in galanin N-terminal fragment (1-15)-mediated effects were studied with positron emission tomography for in vivo imaging, and we analysed the ventral tegmental area and nucleus accumbens. Galanin N-terminal fragment (1-15) had effects on the mRNA expression of the dopamine transporters Dat and Vmat2; the C-Fos gene; the dopamine receptors D1, D2, D3, D5; and the galanin receptors 1 and 2. Results: Galanin N-terminal fragment (1-15) at a concentration of 3 nmol induced a strong anhedonia-like phenotype in all tests. The involvement of galanin receptor 2 was demonstrated with the galanin receptor 2 antagonist M871 (3 nmol). The 18F-fluorodeoxyglucose positron emission tomography images indicated the action of galanin N-terminal fragment (1-15) over several nuclei of the limbic system. Galanin N-terminal fragment (1-15)-mediated effects also involved changes in the expression of Dat, Vmat2, D3 and galanin receptors in the ventral tegmental area as well as the expression of C-Fos, D1, D2 and D3 and TH immunoreactivity in the nucleus accumbens. Conclusions: Our results indicated that galanin N-terminal fragment (1-15) exerts strong anhedonic-like effects and that this effect was accompanied by changes in the dopaminergic mesolimbic system. These results may provide a basis for the development of novel therapeutic strategies using galanin N-terminal fragment (1-15) analogues for the treatment of depression and reward-related diseases.
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| 10. |
- Ott, Michael, 1970-, et al.
(författare)
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Lithium intoxication : Incidence, clinical course and renal function - a population-based retrospective cohort study
- 2016
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 30:10, s. 1008-1019
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Tidskriftsartikel (refereegranskat)abstract
- When prescribing lithium, the risk of toxicity remains a concern. In this study, we examined a cohort of patients exposed to lithium between 1997 and 2013. The aims of this study were to determine the frequency of lithium intoxication and to evaluate the clinical course and changes in renal function. Of 1340 patients, 96 had experienced at least one episode of lithium levels ⩾1.5 mmol/L, yielding an incidence of 0.01 per patient-year. Seventy-seven patients available for review had experienced 91 episodes, of whom 34% required intensive care and 13% were treated with haemodialysis. There were no fatalities. Acute kidney injury occurred, but renal function at baseline was not different to renal function after the episode. Renal impairment was often associated with co-morbidities and other factors. Both intermittent and continuous-venovenous haemodialysis were used, but the clearance of continuous-venovenous haemodialysis can be too low in cases where large amounts of lithium have been ingested. Saline and forced diuresis have been used and are safe. Lithium intoxication seems rare and can be safely managed in most cases. Physicians should not withhold lithium for fear of intoxication in patients who benefit from it. Yet, physicians should have a low threshold to screen for toxicity.
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