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Silje Skrede's picture

Silje Skrede

Professor, NORMENT
  • E-mailSilje.Skrede@uib.no
  • Phone+47 480 93 727
  • Visitor Address
    Haukeland universitetssykehus, Laboratoriebygget
  • Postal Address
    Postboks 7804
    5020 Bergen

Antipsychotic agents, while proving beneficial for many patients suffering from schizophrenia bipolar disorder, have recognized metbolic adverse effects such as increased appetite, weight gain, diabetes and dyslipidemia. The overall aim of my research has been to idenify molecular mehcanisms mediating these metabolic effects, with particular emphasis on effects on gene expression. Results from cultured cells and animal models show how some antipsychotic agents can activate regulatory mechanisms in appetite control centers in the hypothalamus, as well as genes encoding rate-limiting enzymes of lipid synthesis in peripheral tissues such as the liver and adipose tissues. Revealing the impact of antipsychotic agents at this detailed level may aid future development of drugs with less harmful side effects. 

Interestingly, many of the same biological pathways are interesting in the context of sleep and biological rhythms. Exeriments performed by the Bergen Stress and Sleep Group have demonstrated how disruption of biological rhytms through forced shift work in the rat stimulated the expression of lipid synthesis-related genes in the liver. Furthermore, altered expression of so-called clock genes may be important both in the central nervous system and in peripheral tissues. 

In addition, since 2011 I have been acting as co-ordinator and analytic adviser for the biobank belonging to the BestIntro (Bergen-Stavanger-Innsbruck-Trondheim) study. Approximately 6000 biological samples have been collected from patients included in this randomized controlled trial, which aims to compare clinical and adverse effects of three different antipsychotic agents. 

Academic article
  • 2019. One-Year Treatment with Olanzapine Depot in Female Rats: Metabolic Effects. International Journal of Neuropsychopharmacology. 358-369.
  • 2019. Exploring lithium's transcriptional mechanisms of action in bipolar disorder: a multi-step study. Neuropsychopharmacology. 1-9.
  • 2018. Increase in serum HDL level is associated with less negative symptoms after one year of antipsychotic treatment in first-episode psychosis. Schizophrenia Research. 253-260.
  • 2017. Subchronic olanzapine exposure leads to increased expression of myelination-related genes in rat fronto-medial cortex. Translational psychiatry.
  • 2017. No escaping the rat race: simulated night shift work alters the time-of-day variation in BMAL1 translational activity in the prefrontal cortex. Frontiers in Neural Circuits. 1-12.
  • 2016. Shift in food intake and changes in metabolic regulation and gene expression during simulated night-shiftwork: A rat model. Nutrients. 1-13.
  • 2016. Implication of NOTCH1 Gene in Susceptibility to Anxiety and Depression among Sexual Abuse Victims. Translational psychiatry.
  • 2016. Genetic evidence for a role of the SREBP transcription system and lipid biosynthesis in schizophrenia and antipsychotic treatment. European Neuropsychopharmacology. 589-598.
  • 2016. Blue-blocking glasses as additive treatment for mania: A randomized placebo-controlled trial. Bipolar Disorders. 221-232.
  • 2016. A rodent model of night-shift work induces short-term and enduring sleep and electroencephalographic disturbances. Journal of Biological Rhythms. 48-63.
  • 2015. The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells. Stem Cell Research. 530-541.
  • 2015. Olanzapine depot exposure in male rats: Dose-dependent lipogenic effects without concomitant weight gain. European Neuropsychopharmacology. 923-932.
  • 2015. Incident users of antipsychotic agents and future use of cholesterol-lowering drugs: An observational, pharmacoepidemiologic study. Journal of Clinical Psychiatry. e111-e116.
  • 2015. Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine. Journal of Psychopharmacology. 1280-1289.
  • 2014. Olanzapine depot formulation in rat: a step forward in modelling antipsychotic-induced metabolic adverse effects. International Journal of Neuropsychopharmacology. 91-104.
  • 2014. Blocking blue light during mania - markedly increased regularity of sleep and rapid improvement of symptoms: A case report. Bipolar Disorders. 894-898.
  • 2014. Antileukaemic effect of PI3K-mTOR inhibitors in acute myeloid leukaemia-gene expression profiles reveal CDC25B expression as determinate of pharmacological effect. British Journal of Haematology. 200-211.
  • 2013. Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1. PLOS ONE. 10 pages.
  • 2013. Antipsychotic-induced increase in lipid biosynthesis: activation through inhibition? Journal of Lipid Research.
  • 2012. Olanzapine, but not aripiprazole, weight-independently elevates serum triglycerides and activates lipogenic gene expression in female rats. International Journal of Neuropsychopharmacology. 163-179.
  • 2012. Lipid-lowering effects of tetradecylthioacetic acid in antipsychotic-exposed, female rats: challenges with long-term treatment. PLOS ONE. 11 pages.
  • 2012. Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat. Psychopharmacology. 783-794.
  • 2011. Olanzapine-induced hyperphagia and weight gain associate with crexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation. PLOS ONE. 9 pages.
  • 2011. Lipogenic effects of psychotropic drugs: focus on the SREBP system. Frontiers in Bioscience. 49-60.
  • 2009. Psychotropic drugs up-regulate the expression of cholesterol transport proteins including ApoE in cultured human CNS- and liver cells. BMC Pharmacology.
  • 2009. Acute clozapine exposure in vivo induces lipid accumulation and marked sequential changes in the expression of SREBP, PPAR, and LXR target genes in rat liver. Psychopharmacology. 73-84.
  • 2006. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs. BMC Neuroscience.
  • 2005. Antipsychotic drugs activate SREBP-regulated expression of lipid biosynthetic genes in cultured human glioma cells: a novel mechanism of action? The Pharmacogenomics Journal. 298-304.
  • 2003. Schizofreni og membranpatologi - har antipsykotika en rolle i "membranteorien"? Tidsskrift for Den norske legeforening. in press.
Report
  • 2015. Nye brukere av antipsykotika og utvikling av diabetes mellitus. SAMBA/14/15. SAMBA/14/15. .
Academic lecture
  • 2016. Simulated night work alters clock gene expression in central and peripheral tissue in rats.
  • 2016. Implication of NOTCH1 Gene in Comorbid Anxiety and Depression Symptoms in a Sample of Sexual Abuse Victims.
  • 2015. Night work - disturbances in sleep and circadian rhythm parameters. An animal model.
Editorial
  • 2013. Antipsychotic-induced increase in lipid biosynthesis: activation through inhibition? Journal of Lipid Research. 307-309.
Short communication
  • 2019. Short communication: Distribution of psychotropic drugs into lipoproteins. Therapeutic Drug Monitoring. 766-771.
Masters thesis
  • 2018. Gene Expression Changes in Rat Brain Following Long-term Antipsychotic Drug Exposure.
Popular scientific article
  • 2018. Virker antipsykotika gjennom stimulering av myelinproduksjon i hjernen? BestPractice Psykiatri/Nevrologi/Geriatri.
  • 2018. Selektive serotonin-reopptaks-hemmere (SSRI) og blødningsrisiko. Utposten.
Letter to the editor
  • 2019. Stability of antidepressants and antipsychotics in gel separator tubes. Therapeutic Drug Monitoring. 249-250.
Doctoral dissertation
  • 2012. Developing a rodent model for antipsychotic-induced metabolic adverse effects.
Abstract
  • 2016. Simulated night work alters clock gene expression in central and peripheral tissue in rats. Journal of Sleep Research. 57-57.
Poster
  • 2018. Extending the photoperiod impacts circadian rhythmicity and gene expression in prefrontal cortex and retina- Impact of exposure to blue-enriched light. .
  • 2018. Extended photoperiod alters sleep and expression of synaptic plasticity-associated genes. The impact of blue-enriched light.
  • 2018. Extended photoperiod alters circadian rhythmicity and expression of neuroplasticity markers. The impact of blue-enriched light.
  • 2017. The influence of 3 weeks of antipsychotic treatment on cell adhesion molecules in drug naive patients with schizophrenia spectrum disorder .
Academic literature review
  • 2014. A critical review of pro-cognitive drug targets in psychosis: convergence on myelination and inflammation.

More information in national current research information system (CRIStin)