| 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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