Person: Linnman, Nils
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Linnman
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Nils
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Linnman, Nils
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Publication Nocebo Effect in Randomized Clinical Trials of Antidepressants in Children and Adolescents: Systematic Review and Meta-Analysis(Frontiers Media S.A., 2014) Rojas-Mirquez, Johanna Carolina; Rodriguez-Zuñiga, Milton Jose Max; Bonilla-Escobar, Francisco Javier; Garcia-Perdomo, Herney Andres; Petkov, Mike; Becerra, Lino; Borsook, David; Linnman, NilsObjective:: To compare the incidence of adverse events between active and placebo arms of randomized clinical trials in depressive children and adolescents (C&A) with antidepressant treatments, in order to look for similarities in both groups that allow to establish a possible nocebo effect. Methods:: Systematic search strategy (January 1974–March 2013) in electronic databases, conference abstracts, and reference list of systematic reviews and included studies to identify parallel randomized placebo-controlled trials of antidepressants in C&A (<19 years) with major depressive disorder, and one or more interventions of any orally administered antidepressant. The pooled adverse events were calculated based on a fixed-effect model and statistical analysis involved the risk ratio (RR) of adverse events, with 95% confidence intervals (95% CI). Results:: Sixteen studies were included in the review, of which seven studies with a sample of 1911 patients had data to include in the meta-analysis. There was similar risk for the incidence of adverse events between non-active and active group (global RR 1.04, 95% CI: 0.97–1.11). Conclusion:: Depressive C&A allocated to placebo or active group had similar risk to develop adverse events. These similarities in both groups are attributed to the nocebo effect. It is of note that defining “nocebo” effects is challenging in clinical populations because adverse effects may be attributed to the intervention or may be manifestation of the disease itself. The inclusion of a no-treatment arm may be warranted. Nocebo effects are likely when adverse events of placebo mimic the adverse events of active treatment, as was the case here.Publication Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow(Public Library of Science, 2016) Linnman, Nils; Catana, Ciprian; Svärdsudd, Kurt; Appel, Lieuwe; Engler, Henry; Långström, Bengt; Sörensen, Jens; Furmark, Tomas; Fredrikson, Mats; Borsook, David; Peterson, MagnusSubstance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.Publication Molecular and functional PET-fMRI measures of placebo analgesia in episodic migraine: Preliminary findings(Elsevier, 2017) Linnman, Nils; Catana, Ciprian; Petkov, Mike P.; Chonde, Daniel Burje; Becerra, Lino; Hooker, Jacob; Borsook, DavidPain interventions with no active ingredient, placebo, are sometimes effective in treating chronic pain conditions. Prior studies on the neurobiological underpinnings of placebo analgesia indicate endogenous opioid release and changes in brain responses and functional connectivity during pain anticipation and pain experience in healthy subjects. Here, we investigated placebo analgesia in healthy subjects and in interictal migraine patients (n = 9) and matched healthy controls (n = 9) using 11C-diprenoprhine Positron Emission Tomography (PET) and simultaneous functional Magnetic Resonance Imaging (fMRI). Intravenous saline injections (the placebo) led to lower pain ratings, but we did not find evidence for an altered placebo response in interictal migraine subjects as compared to healthy subjects.