| 1. |
- Aklillu, Eleni, et al.
(författare)
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Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression.
- 2009
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Ingår i: Pharmacogenetics and genomics. - 1744-6872. ; 19:4, s. 267-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Monoamine oxidase-A (MAO-A) is a key mitochondrial enzyme that metabolizes biogenic amine neurotransmitters such as dopamine and serotonin. Individuals with atypical depression (AD) are particularly responsive to treatment with MAO inhibitors (MAOIs). Biomarker tests are essential for prompt diagnosis of AD, and to identify those with an altered brain neurotransmitter metabolism who may selectively respond to MAOI therapy. METHODS: In a sample of 118 Scandinavian patients with treatment-resistant depression who are naive to MAOI therapy, we investigated the associations between a common MAOA functional promoter polymorphism (MAOA-uVNTR), cerebrospinal fluid (CSF) neurotransmitter metabolites, and AD susceptibility. The metabolites for dopamine (homovanillic acid, HVA), serotonin (5-hydroxyindoleacetic acid) and noradrenaline (3-methoxy-4-hydroxyphenylglycol) were measured in the CSF. RESULTS: AD was associated with the female sex and a higher HVA in CSF (P=0.008). The carriers of the MAOA-uVNTR short allele were significantly overrepresented among women with AD (P=0.005; odds ratio=4.76; 95% confidence interval=1.5-13.1; statistical power=80.0%). Moreover, the MAOA-uVNTR genotype significantly influenced the HVA concentration (P=0.01) and showed a strong trend in relation to 5-hydroxyindoleacetic acid concentration (P=0.057) in women. The mediational statistical analyses showed the CSF-HVA concentration as a key driver of the relationship between MAOA-uVNTR genotype and AD. CONCLUSION: The association of the MAOA-uVNTR with both susceptibility to AD and dopamine metabolite (HVA) concentration lends further biological plausibility for high MAO-A enzyme activity as a mechanistic factor for genetic predisposition to AD through altered dopamine turnover. Our observations provide new evidence on the in-vivo functional significance of the MAOA-uVNTR short allele as a high activity variant.
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| 2. |
- Backlund, Lena, et al.
(författare)
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Identifying predictors for good lithium response - A retrospective analysis of 100 patients with bipolar disorder using a life-charting method.
- 2009
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 0924-9338. ; 24:3, s. 171-7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Our aim was to investigate bipolar patients in order to test the validity of various outcome measures and to identify prognostic predictors for pharmacological treatment. MATERIAL AND METHOD: One hundred patients were interviewed using a computerized life-charting program in a descriptive, retrospective analysis. The concept "Burden of illness" was defined as a combination of severity and duration of episodes. Response to treatment was defined as the difference in burden before and after treatment, a low burden during treatment, and freedom of episodes for at least 3 years after insertion of treatment. RESULTS: The absence of mixed episodes and a high initial burden predicted a good response measured as the difference in burden. If remission for 3 years or a low burden during lithium treatment was used, the absence of rapid cycling and of mixed episodes were the most important predictors. The severity of illness before treatment had no impact. DISCUSSION AND CONCLUSION: We suggest the use of absolute measures of severity during treatment as the most appropriate measure of the outcome. Furthermore, our data provide corroboration that treatment with lithium ameliorates the prognosis of the illness, but that mixed episodes and rapid cycling predict a poorer response to lithium.
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| 3. |
- Chavali, Pavithra Lakshminarasimhan, et al.
(författare)
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Nuclear orphan receptor TLX induces Oct-3/4 for the survival and maintenance of adult hippocampal progenitors upon hypoxia.
- 2011
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 286:11, s. 9393-9404
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia promotes neural stem cell proliferation, the mechanism of which is poorly understood. Here, we have identified the nuclear orphan receptor TLX as a mediator for proliferation and pluripotency of neural progenitors, upon hypoxia. We find an enhanced early protein expression of TLX under hypoxia potentiating sustained proliferation of neural progenitors. Moreover, TLX induction upon hypoxia in differentiating conditions leads to increased proliferation and stem cell like phenotype along with coexpression with neural stem cell markers. Following hypoxia, TLX is recruited to Oct-3/4 proximal promoter, augmenting the gene transcription and promoting progenitor proliferation and pluripotency. Knock-down of Oct-3/4 significantly reduced TLX mediated proliferation, highlighting their interdependence in regulating progenitor pool. Additionally, TLX synergizes with bFGF to sustain cell viability upon hypoxia, since the knock-down of TLX along with the withdrawal of growth factor results in cell death. This can be attributed to the activation of Akt signaling pathway by TLX, the depletion of which results in reduced proliferation of progenitor cells. Cumulatively, the data presented here demonstrate a new role for TLX in neural stem cell proliferation and pluripotency upon hypoxia.
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| 4. |
- Chiragwandi, Zackary, 1968, et al.
(författare)
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Properties of a bio-photovoltaic nano-device
- 2008
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 112:48, s. 18717-18721
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Tidskriftsartikel (refereegranskat)abstract
- Properties of an on-chip photovoltaic nanodevice are demonstrated. The dyes comprise green florescent proteins(GFP). Dependence of recently reported zero external potential bias (ZEPB) photocurrent (I) on temperature,power, and wavelength (λ) is shown. Correlation between UV-vis spectrum of the GFP and the ZEPB I(λ)of the device is reported. The temperature dependence suggests the ZEPB photocurrent to reflect a liquidcrystal type ordering where the current declines monotonically with increasing temperature. The influence ofan external bias on the photocurrent is demonstrated. The resulting light-induced current is analyzed in termsof resistive and quantum mechanical contributions.
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| 5. |
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| 6. |
- Elmi, Muna, 1978, et al.
(författare)
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TLX activates MASH1 for induction of neuronal lineage commitment of adult hippocampal neuroprogenitors.
- 2010
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 45:2, s. 121-31
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Tidskriftsartikel (refereegranskat)abstract
- The orphan nuclear receptor TLX has been proposed to act as a repressor of cell cycle inhibitors to maintain the neural stem cells in an undifferentiated state, and prevents commitment into astrocyte lineages. However, little is known about the mechanism of TLX in neuronal lineage commitment and differentiation. A majority of adult rat hippocampus-derived progenitors (AHPs) cultured in the presence of FGF express a high level of TLX and a fraction of these cells also express the proneural gene MASH1. Upon FGF withdrawal, TLX rapidly decreased, while MASH1 was intensely expressed within 1h, decreasing gradually to disappear at 24h. Adenoviral transduction of TLX in AHP cells in the absence of FGF transiently increased cell proliferation, however, later resulted in neuronal differentiation by inducing MASH1, Neurogenin1, DCX, and MAP2ab. Furthermore, TLX directly targets and activates the MASH1 promoter through interaction with Sp1, recruiting co-activators whereas dismissing the co-repressor HDAC4. Conversely, silencing of TLX in AHPs decreased beta-III tubulin and DCX expression and promoted glial differentiation. Our results thus suggest that TLX not only acts as a repressor of cell cycle and glial differentiation but also activates neuronal lineage commitment in AHPs.
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| 7. |
- Eriksson, Maria Christina, 1981, et al.
(författare)
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Long-term effects of Internet-delivered cognitive behavioral therapy for depression in primary care - the PRIM-NET controlled trial.
- 2017
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Ingår i: Scandinavian journal of primary health care. - : Informa UK Limited. - 1502-7724 .- 0281-3432. ; 35:2, s. 126-136
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Tidskriftsartikel (refereegranskat)abstract
- Internet-delivered cognitive behavioral therapy (ICBT) is recommended as an efficient treatment alternative for depression in primary care. However, only few previous studies have been conducted at primary care centers (PCCs). We evaluated long-term effects of ICBT treatment for depression compared to treatment as usual (TAU) in primary care settings.Randomized controlled trial.Patients were enrolled at16 PCCs in south-west Sweden.Patients attending PCCs and diagnosed with depression (n=90).Patients were assessed by a primary care psychologist/psychotherapist and randomized to ICBT or TAU. The ICBT included an ICBT program consisting of seven modules and weekly therapist e-mail or telephone support during the 3-month treatment period.Questionnaires on depressive symptoms (BDI-II), quality of life (EQ-5D) and psychological distress (GHQ-12) were administered at baseline, with follow-ups at 3, 6 and 12 months. Antidepressants and sedatives use, sick leave and PCC contacts were registered.Intra-individual change in depressive symptoms did not differ between the ICBT group and the TAU group during the treatment period or across the follow-up periods. At 3-month follow-up, significantly fewer patients in ICBT were on antidepressants. However, the difference leveled out at later follow-ups. There were no differences between the groups concerning psychological distress, sick leave or quality of life, except for a larger improvement in quality of life in the TAU group during the 0- to 6-month period.ICBT with weekly minimal therapist support in primary care can be equally effective as TAU among depressed patients also over a 12-month period.The trial was registered in the Swedish Registry, researchweb.org, ID number 30511.
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| 8. |
- Eriksson, Olle, et al.
(författare)
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Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria.
- 2006
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Ingår i: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 0925-4927 .- 1872-7506. ; 146:2, s. 107-16
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Tidskriftsartikel (refereegranskat)abstract
- The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.
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| 9. |
- Eriksson, Olle, 1954-, et al.
(författare)
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Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.
- 2016
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls.Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women.Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain".There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation.Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.
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| 10. |
- Goodwin, GM, et al.
(författare)
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Aripiprazole in patients with bipolar mania and beyond: an update of practical guidance
- 2011
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Ingår i: CURRENT MEDICAL RESEARCH AND OPINION. - 0300-7995. ; 27:12, s. 2285-2299
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Aripiprazole is an atypical antipsychotic with a pharmacological and clinical profile distinct from other atypical antipsychotics. SCOPE: A European multidisciplinary advisory panel of university-based experts in bipolar disorders convened in April 2010 to review new clinical guidelines for the management of mania and the role of aripiprazole in its treatment. This report describes the consensus reached on how best to use aripiprazole in the treatment of mania. FINDINGS: Current guidelines recommending aripiprazole for first-line treatment of mania have not generally translated to clinical practice. The panel agreed that clinicians may not feel sufficiently knowledgeable on how to use aripiprazole effectively in mania, and that the perception that aripiprazole is less sedating than other antipschotics may hamper its use. There was consensus about the importance of ensuring that clinicians understood the distinction between antimanic efficacy and sedation. Most acutely manic patients may require night-time sedation, but continuous daytime sedation is not necessarily indicated and may interfere with long-term compliance. If sedation is necessary, guidelines recommend the use of adjunctive benzodiazepines only for a short-time. CONCLUSIONS: Clinical practice guidelines widely recommend aripiprazole as a first-line treatment for mania. Although clinical trials may not represent all patient subpopulations, they show that aripiprazole is well tolerated and has a long-term stabilizing potential. The successful use of aripiprazole rests on using the appropriate initial dose, titrating and adjusting the dose as needed and using appropriate concomitant medication to minimize any short-term adverse events. Low incidence of sedation makes aripiprazole a reasonable long-term treatment choice. If short-term sedation is required an adjunctive sedative agent can be added and removed when no longer needed. Clinical considerations should influence treatment choice, and a better distinction between sedation and antimanic effects should be an educational target aimed to overcome potential barriers for using non-sedative antimanic agents such as aripiprazole.
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| 11. |
- Hayashi, Amiko, et al.
(författare)
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Calcium-dependent intracellular signal pathways in primary cultured adipocytes and ANK3 gene variation in patients with bipolar disorder and healthy controls.
- 2015
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 20, s. 931-40
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a chronic psychiatric disorder of public health importance affecting >1% of the Swedish population. Despite progress, patients still suffer from chronic mood switches with potential severe consequences. Thus, early detection, diagnosis and initiation of correct treatment are critical. Cultured adipocytes from 35 patients with BD and 38 healthy controls were analysed using signal pathway reporter assays, that is, protein kinase C (PKC), protein kinase A (PKA), mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)), Myc, Wnt and p53. The levels of activated target transcriptional factors were measured in adipocytes before and after stimulation with lithium and escitalopram. Variations were analysed in the loci of 25 different single-nucleotide polymorphisms (SNPs). Activation of intracellular signals in several pathways analysed were significantly higher in patients than in healthy controls upon drug stimulation, especially with escitalopram stimulation of PKC, JNK and Myc, as well as lithium-stimulated PKC, whereas no meaningful difference was observed before stimulation. Univariate analyses of contingency tables for 80 categorical SNP results versus diagnoses showed a significant link with the ANK3 gene (rs10761482; likelihood ratio χ2=4.63; P=0.031). In a multivariate ordinal logistic fit for diagnosis, a backward stepwise procedure selected ANK3 as the remaining significant predictor. Comparison of the escitalopram-stimulated PKC activity and the ANK3 genotype showed them to add their share of the diagnostic variance, with no interaction (15% of variance explained, P<0.002). The study is cross-sectional with no longitudinal follow-up. Cohorts are relatively small with no medication-free patients, and there are no 'ill patient' controls. It takes 3 to 4 weeks of culture to expand adipocytes that may change epigenetic profiles but remove the possibility of medication effects. Abnormalities in the reactivity of intracellular signal pathways to stimulation and the ANK3 genotype may be associated with pathogenesis of BD. Algorithms using biological patterns such as pathway reactivity together with structural genetic SNP data may provide opportunities for earlier detection and effective treatment of BD.
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| 12. |
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| 13. |
- Ishima, T., et al.
(författare)
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Abnormal gene expression of BDNF, but not BDNF-AS, in iPSC, neural stem cells and postmortem brain samples from bipolar disorder
- 2021
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327. ; 290, s. 61-64
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Tidskriftsartikel (refereegranskat)abstract
- Background: Brain-derived neurotrophic factor (BDNF) antisense RNA (BDNF-AS) was identified as naturally conserved non-coding antisense RNA that suppresses the transcription of BDNF. Methods: We measured the expression of BDNF mRNA and BDNF-AS mRNA in iPSC and NSC from bipolar disorder (BD) patients and healthy control subjects, and postmortem brain samples such as the corpus callosum, the Brodmann area (BA8), and BA46 from BD patients and age-and sex-matched controls. Results: The expression of BDNF mRNA in iPSC from BD patients (n = 6) was significantly lower than that of control subjects (n = 4) although the expression of BDNF mRNA in NSC from BD patients was significantly higher than that of control subjects. In contrast, there were no changes in the expression of BDNF-AS mRNA in both iPSC and NSC between two groups. The expression of BDNF mRNA in the BA46 from BD patients (n = 35) was significantly lower than that of controls (n = 34) although the expression of BDNF mRNA in the corpus callosum and BA8 was not different between two groups (n = 15). In contrast, there were no changes in expression of BDNF-AS mRNA in the three brain regions between two groups. Interestingly, there were significant positive correlations between BDNF mRNA expression and BDNF-AS mRNA expression in the postmortem brain samples. Limitations: Sample sizes are relatively low. Conclusions: Our data suggest that abnormalities in the expression of BDNF, but not BDNF-AS, play a role in the pathogenesis of BD.
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| 14. |
- Izsak, Julia, et al.
(författare)
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Robust generation of person-specific, synchronously active neuronal networks using purely isogenic human iPSC-3D neural aggregate cultures
- 2019
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Reproducibly generating human induced pluripotent stem cell-based functional neuronal circuits, solely obtained from single individuals, poses particular challenges to achieve personalized and patient specific functional neuronal in vitro models. A hallmark of functional neuronal assemblies, synchronous neuronal activity, can be non-invasively studied by microelectrode array (MEA) technology, reliably capturing physiological and pathophysiological aspects of human brain function. In our here presented manuscript, we demonstrate a procedure to generate 3D neural aggregates comprising astrocytes, oligodendroglial cells, and neurons obtained from the same human tissue sample. Moreover, we demonstrate the robust ability of those neurons to create a highly synchronously active neuronal network within 3 weeks in vitro, without additionally applied astrocytes. The fusion of MEA-technology with functional neuronal circuits solely obtained from one individual's cells represent isogenic person-specific human neuronal sensor chips that pave the way for specific personalized in vitro neuronal networks as well as neurological and neuropsychiatric disease modeling.
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| 15. |
- Kishida, Ikuko, et al.
(författare)
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Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression.
- 2007
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 32:10, s. 2143-51
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p=0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p=0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p=0.0001) and L/S (p=0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p=0.002) and L/S subjects (p=0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders.
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| 16. |
- Koulentianos, Dimitris, 1987, et al.
(författare)
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Formation and relaxation of K-2 and K-2V double-core-hole states in n-butane
- 2022
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 157:4
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Tidskriftsartikel (refereegranskat)abstract
- Using a magnetic bottle multi-electron time-of-flight spectrometer in combination with synchrotron radiation, double-core-hole pre-edge and continuum states involving the K-shell of the carbon atoms in n-butane ( n-C4H10) have been identified, where the ejected core electron(s) and the emitted Auger electrons from the decay of such states have been detected in coincidence. An assignment of the main observed spectral features is based on the results of multi-configurational self-consistent field (MCSCF) calculations for the excitation energies and static exchange (STEX) calculations for energies and intensities. MCSCF results have been analyzed in terms of static and dynamic electron relaxation as well as electron correlation contributions to double-core-hole state ionization potentials. The analysis of applicability of the STEX method, which implements the one-particle picture toward the complete basis set limit, is motivated by the fact that it scales well toward large species. We find that combining the MCSCF and STEX techniques is a viable approach to analyze double-core-hole spectra.
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| 17. |
- Langworth, Sven, et al.
(författare)
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Efficacy and tolerability of reboxetine compared with citalopram: a double-blind study in patients with major depressive disorder.
- 2006
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Ingår i: Journal of clinical psychopharmacology. - Philadelphia : Ovid Technologies (Wolters Kluwer Health). - 0271-0749 .- 1533-712X. ; 26:2, s. 121-7
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to compare efficacy and tolerability of the selective noradrenaline reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram, in the treatment of major depressive disorder (MDD). In total, 357 outpatients with MDD were randomized to treatment with reboxetine 8-10 mg or citalopram 20-40 mg per day during 24 weeks. Primary end-point was change from baseline in the Hamilton Depression Rating Scale (HAM-D, 21 items). Sexual function/dysfunction was measured by the Sexual Function scale (SF). Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores: reboxetine with -21.4 and citalopram with -22.1 points (NS). LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine (-19.6 vs. -17.8; P = 0.034). The response rate was 90.3% for reboxetine and 92.7% for citalopram (NS). The most common side effect in the reboxetine group was dry mouth, and in the citalopram group sexual dysfunction. At week 24, anorgasmia was reported by 5.9% of the sexually active women in the reboxetine group vs 39% in the citalopram group. The dropout number was 91 in the reboxetine group, and 54 in the citalopram group. To summarize, both treatments gave a satisfactory antidepressant effect. The side effect profile differed between the groups, with a notably high prevalence of sexual dysfunctions in the citalopram group. The high number of dropouts in the reboxetine group, is considered as a result of the non-titration starting dose of 8 mg reboxetine per day, which gave a high incidence of early side-effects.
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| 18. |
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| 19. |
- Muhwezi, W W, et al.
(författare)
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Detection of major depression in Ugandan primary health care settings using simple questions from a subjective well-being (SWB) subscale
- 2007
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Ingår i: Soc Psychiatry Psychiatr Epidemiol. ; 42:1, s. 61-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore whether the 4-item subjective well-being subscale could be used to detect a major depressive illness. Secondly, to describe the prevalence and characteristics of depressed health care attendees at primary healthcare centres. METHOD: Using a descriptive, cross-sectional study design, we interviewed 199 consecutive patients about their socio-demographics, subjective well-being (SWB), major depressive illness symptoms and depression severity. The instruments used were translated into Luganda. RESULTS: Point prevalence of a current Major Depressive Episode (MDE) was 31.6%. Using a one week reference period, we found that experiencing a lot of distress, having less energy or poor health, having poor emotional and psychological adjustment and not being satisfied with life were significantly more common among patients with a current MDE. The 4-item SWB subscale detected depression of up to 87.1% (95% CI: 0.818-0.923). In logistic regression, all four SWB items predicted a current MDE. CONCLUSION: Major depressive illness is a common at primary healthcare level in Uganda. Four simple questions reflecting SWB items have potential to detect diagnosable patients likely to have a current MDE, making general screening procedures less necessary.
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| 20. |
- Nakasujja, N., et al.
(författare)
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Cognitive Dysfunction among HIV Positive and HIV Negative Patients with Psychosis in Uganda
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive impairment is an established phenomenon in HIV infected individuals and patients that have psychosis. However there is need to establish the severity of the impairment if patients are co morbid with both conditions. Aim: To compare cognitive function among HIV positive individuals and HIV negative individuals with psychosis. Methods: We recruited patients with psychosis at two national referral hospitals. A standardized demographics questionnaire and psychiatric, physical, and laboratory assessments were conducted. Types of psychosis were diagnosed using the Mini International Neuropsychiatric Inventory-PLUS while cognitive functioning was determined using the Mini mental state examination (MMSE) and a neuropsychological test battery. Follow-up assessments on cognitive function and severity of psychiatric illness were performed at 3 and 6 months. Pairwise comparison and multivariable logistic regression analysis were used to determine the differences between the HIV positive and HIV negative individuals. Results: There were 156 HIV positive and 322 HIV negative participants. The mean age was 33 years for the HIV positive group and 29 years for the HIV negative group (p<0.001). The HIV positive individuals were almost three times (OR = 2.62 CI 95% 1.69-4.06) more likely to be cognitively impaired on the MMSE as well as the following cognitive tests:- WHO-UCLA Auditory Verbal Learning Test (OR 1.79, 95% CI 1.09-2.92), Verbal Fluency (OR 3.42, 95% CI 2.24-5.24), Color Trails 1 (OR 2.03, 95% CI 1.29-3.02) and Color Trails 2 (OR 3.50 95% 2.00-6.10) all p = 0.01. There was improvement in cognitive function at follow up; however the impairment remained higher for the HIV positive group (p<0.001). Conclusion: Cognitive impairment in psychosis was worsened by HIV infection. Care plans to minimize the effect of this impairment should be structured for the management of individuals with HIV and psychosis.
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| 21. |
- Pålsson, Erik, 1975, et al.
(författare)
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Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls
- 2015
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X. ; 25:1, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Goran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. (C) 2014 Elsevier B.V. and ECNP. All rights reserved.
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| 22. |
- Roth, Göran, et al.
(författare)
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A longitudinal study of PTSD in a sample of adult mass-evacuated Kosovars, some of whom returned to their home country.
- 2006
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 0924-9338. ; 21:3, s. 152-9
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Tidskriftsartikel (refereegranskat)abstract
- PTSD among a sample of mass-evacuated adults from Kosovo was studied using a prospective design with a baseline study and follow-ups at 3 and 6 months in Sweden, and with an additional follow-up after 1.5 years in both Sweden and Kosovo. Trauma events and PTSD-related symptoms were measured by the Harvard Trauma Questionnaire (HTQ). At the additional follow-up after 1.5 years the same measure (HTQ) was used as well as clinical diagnostic interviews with the SCID instrument and measurement of saliva cortisol levels. Thirty-seven percent had PTSD-related symptoms at baseline. Morbidity increased at the three follow-ups. About 80% of the participants had PTSD at the additional follow-up after 1.5 years. The HTQ results were confirmed by clinical diagnoses and the participants diagnosed with PTSD also had low saliva cortisol levels. The results are discussed in terms of trauma, time needed to develop PTSD, post-migration stress and selection mechanisms.
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| 23. |
- Schlaepfer, T. E., et al.
(författare)
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The hidden third: improving outcome in treatment-resistant depression
- 2012
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Ingår i: Journal of Psychopharmacology. - 0269-8811. ; 26:5, s. 587-602
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Tidskriftsartikel (refereegranskat)abstract
- Treatment-resistant depression (TRD) presents many challenges for both patients and physicians. This review aims to evaluate the current status of the field of TRD and reflects the main findings of a consensus meeting held in September 2009. Literature searches were also conducted using PubMed and EMBASE. Abstracts of the retrieved articles were reviewed independently by the authors for inclusion. Evaluation of the clinical evidence in TRD is complicated by the absence of a validated definition, and there is a need to move away from traditional definitions of remission based on severity of symptoms to one that includes normalisation of functioning. One potential way of improving treatment of TRD is through the use of predictive biomarkers and clinical variables. The advent of new treatments may also help by focusing on neurotransmitters other than serotonin. Strategies such as the switching of antidepressants, use of combination therapy with lithium, atypical antipsychotics and other pharmacological agents can improve outcomes, and techniques such as deep brain stimulation and vagus nerve stimulation have shown promising early results. Despite consistent advances in the pharmacotherapy of mood disorders in the last decade, high rates of TRD are still a challenging aspect of overall management.
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| 24. |
- Skärsäter, Ingela, 1952, et al.
(författare)
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Sense of coherence and recovery from major depression: a four-year follow-up
- 2009
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Ingår i: Archives of Psychiatric Nursing. - 0883-9417. ; 23:2, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this longitudinal exploratory study was to identify and follow persons with the first episode of major depression (MD) to determine whether sense of coherence (SOC) changes over time. An additional purpose was to assess whether SOC is associated with depressive symptoms, aggression, and functional status either immediately after diagnosis or at 4 years postdiagnosis. The study design was longitudinal; participants participated in semistructured interviews and completed surveys every 6 months starting at diagnosis and concluding 4 years later. The sample consisted of 33 adult patients who were being treated for the first episode of MD according to the Diagnostic and Statistical Manual of Mental Disorders. Twenty-two participants completed all nine sessions. SOC was measured using the SOC scale; depressive symptoms using the Montgomery Asberg Depression Rating Scale; aggression, including the total score and subscales of anger and hostility, using the Aggression Questionnaire-revised Swedish version; and functional status using the Global Assessment of Functioning (GAF) scale and the 36-item Short-Form Health Survey (SF-36). At baseline, SOC was significantly correlated with total aggression (r = -45) and the hostility subscale (r = -.73); baseline SOC was unrelated to depressive symptoms or functional status. SOC increased significantly over time (P < .0001). At the 4-year follow-up, SOC was significantly related to depressive symptoms (r = -.60), the aggression summary score (r = -.65), the anger subscale (r = -.52), the hostility subscale (r = -.77), the GAF (r = .64), and the physical and mental health components of the SF-36 (r = .74 and .72, respectively). The finding that SOC increases as patients recover from MD suggests that treatment of depression may also bolster the patient's ability to cope, in addition to lowering depressive symptoms. The relationship between SOC and aggression in MD, with higher SOC correlated with lower aggression, needs to be examined further.
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| 25. |
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