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  • 1. Allgulander, Christer
    et al.
    Mangano, Richard
    Zhang, Jun
    Dahl, Alv A
    Lepola, Ulla
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Emilien, Gerard
    Efficacy of venlafaxine ER in patients with social anxiety disorder: A double-blind, placebo-controlled, parallel-group comparison with paroxetine2004In: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 19, no 6, p. 387-396Article in journal (Refereed)
    Abstract [en]

    This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n=434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p<0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.

  • 2.
    Annerbrink, K.
    et al.
    University of Gothenburg.
    Hansson, C.
    University of Gothenburg.
    Allgulander, C.
    Karolinska Institute.
    Andersch, S.
    Sahlgrens University Hospital.
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Holm, G.
    Sahlgrens University Hospital.
    Dickson, S.
    University of Gothenburg.
    Eriksson, E.
    Gothenburg University Hospital.
    A possible association between panic disorder and the ghrelin gene in EUROPEAN NEUROPSYCHOPHARMACOLOGY, vol 21, issue , pp S238-S2382011In: EUROPEAN NEUROPSYCHOPHARMACOLOGY, Elsevier , 2011, Vol. 21, p. S238-S238Conference paper (Refereed)
    Abstract [en]

    n/a

  • 3.
    Annerbrink, Kristina
    et al.
    University of Gothenburg.
    Westberg, Lars
    University of Gothenburg.
    Olsson, Marie
    Sahlgrens University Hospital.
    Allgulander, Christer
    Karolinska Institute.
    Andersch, Sven
    University of Gothenburg.
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Holm, Goran
    Sahlgrens University Hospital.
    Eriksson, Elias
    University of Gothenburg.
    Association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder: A replication2010In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 178, no 1, p. 196-198Article in journal (Refereed)
    Abstract [en]

    The association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder was studied in a Swedish sample of 211 patients and 452 controls. We found a significant excess of the Val allele in both male and female patients, the latter but not the former finding being in line with previous studies.

  • 4.
    Annerbrink, Kristina
    et al.
    University of Gothenburg.
    Westberg, Lars
    University of Gothenburg.
    Olsson, Marie
    Apoteket AB.
    Andersch, Sven
    University of Gothenburg.
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Holm, Goran
    Sahlgrens University Hospital.
    Allgulander, Christer
    Karolinska Institute.
    Eriksson, Elias
    University of Gothenburg.
    Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene2011In: PSYCHIATRIC GENETICS, ISSN 0955-8829, Vol. 21, no 2, p. 85-89Article in journal (Refereed)
    Abstract [en]

    Background Orexin A and B are neuropeptides influencing, for example, arousal and respiration. Although panic disorder is characterized by both enhanced proneness for arousal and by respiratory abnormalities, the possible influence of orexin-related genes on the risk of developing this disorder has not been studied until now. Methods We have analyzed the Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls. Results Although the polymorphism in the HCRTR1 did not differ between groups, the Iso allele of the HCRTR2 polymorphism was significantly more frequent in patients than in controls. After the population was divided according to sex, the association between the Iso allele of the Val308Iso polymorphism and panic disorder was observed only in female patients. Conclusion Our results suggest that the HCRTR2 polymorphism may be of importance for the pathophysiology of panic disorder. The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding.

  • 5.
    Bogren, Lennart
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Bogren, Inga-Britt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Ohrt, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Panic disorder and the Defence Mechanism Test2002In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 56, p. 195-199Article in journal (Refereed)
    Abstract [en]

    The aim was to study defence categories according to the modified version of the Defence Mechanism Test (DMTm) and to see if there was a relationship between DMTm and severity of illness. The material consists of 23 patients with panic disorder according to DSM-III-R who participated in a long-term follow-up of two clinical trials. The most common defence categories were repression, denial, disavowal or denial of the threat relation or of the identity of the peripheral person. The patients with denial or polymorphous identification had more severe symptoms and the latter group also were more handicapped by their symptoms. Denial and disavowal or denial of the threat relation may be defence categories, which are not so effective in preventing the individual from experiencing anxiety. Polymorphous identification, although not so common, does not seem to be an appropriate defence among patients with panic disorder.

  • 6.
    Hansson, Caroline
    et al.
    University of Gothenburg, Sweden .
    Annerbrink, Kristina
    University of Gothenburg, Sweden .
    Nilsson, Staffan
    Chalmers, Sweden .
    Bah, Jessica
    University of Gothenburg, Sweden .
    Olsson, Marie
    University of Gothenburg, Sweden .
    Allgulander, Christer
    Karolinska Institute, Sweden .
    Andersch, Sven
    University of Gothenburg, Sweden .
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Eriksson, Elias
    University of Gothenburg, Sweden .
    Dickson, Suzanne L.
    University of Gothenburg, Sweden .
    A possible association between panic disorder and a polymorphism in the preproghrelin gene2013In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 206, no 1, p. 22-25Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups.

  • 7.
    Henningsson, S.
    et al.
    Department of Pharmacology, Göteborg University, Göteborg, Sweden.
    Annerbrink, K.
    Department of Pharmacology, Göteborg University, Göteborg, Sweden.
    Olsson, M.
    Department of Pharmacology, Göteborg University, Göteborg, Sweden.
    Allgulander, C.
    Karolinska Institutet, Neurotec Department, Section of Psychiatry, Stockholm, Sweden.
    Andersch, S.
    Institution of Clinical Neuroscience, Göteborg University, Göteborg, Sweden.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Gustafson, D.
    Institution of Clinical Neuroscience, Göteborg University, Göteborg, Sweden.
    Skoog, I.
    Institution of Clinical Neuroscience, Göteborg University, Göteborg, Sweden.
    Eriksson, E.
    Department of Pharmacology, Göteborg University, Göteborg, Sweden.
    Westberg, L.
    Department of Pharmacology, Göteborg University, Göteborg, Sweden, Department of Pharmacology, Box 431, Göteborg University, 40530 Göteborg, Sweden.
    Absence of the Arg441His polymorphism in the tryptophan hydroxylase 2 gene in adults with anxiety disorders and depression2007In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, ISSN 1552-4841, Vol. 144, no 6, p. 816-817Other (Other academic)
    Abstract [en]

    [No abstract available]

  • 8. Kechagias, Stergios
    et al.
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Kullman, Eric
    Kullman, Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-magtarm.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Almér, Lars-Olof
    Almér, Lars-Olof
    Invärtesmedicin MAS, Malmö.
    En AT-skrivning bör inte enbart ha lätta frågor om vanliga tillstånd!2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, p. 1739-1739Article in journal (Other (popular science, discussion, etc.))
  • 9.
    Nordin, Conny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Gupta, Ramesh
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Cerebrospinal fluid amino acids in pathological gamblers and healthy controls2007In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 56, no 2-3, p. 152-158Article in journal (Refereed)
    Abstract [en]

    Amino acids, such as valine, isoleucine and leucine compete with tyrosine and tryptophan for transport into the brain and might thus affect the central serotonin and catecholamine patterns. Furthermore, the excitatory amino acids glutamic acid, aspartic acid and glycine are known to act on the N-methyl-D-aspartate receptor, which is part of the reward system. Based on these facts, we have explored the role of cerebrospinal fluid (CSF) amino acids in pathological gambling. Concentrations of amino acids were determined in CSF obtained from one female and 11 pathological male gamblers and 11 healthy male controls. In an ANCOVA with best subset regression, pathological male gamblers had higher CSF levels of the excitatory glutamic and aspartic acids, as well as of phenylalanine, isoleucine, citrulline and glycine. A negative contribution of glycine in interaction with the neuraxis distance might mirror a reduced spinal supply or an altered elimination of glycine in pathological gamblers. A decreasing CSF gradient from the first (0-6 ml) to the third (13-18 ml) CSF fraction was found for glutamic acid, glycine, leucine, isoleucine, lysine, ornithine and glutamine in both pathological gamblers and healthy controls. A decreasing gradient was found, however, for aspartic acid and phenylalanine in pathological male gamblers. The altered pattern of CSF amino acids in pathological gamblers might exert an influence on central monoamines as well as on N-methyl-D-aspartate receptor function. Copyright © 2008 S. Karger AG.

  • 10.
    Nordin, Conny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    CSF cholecystokinin, γ-aminobutyric acid and neuropeptide Y in pathological gamblers and healthy controls2007In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 114, no 4, p. 499-503Article in journal (Refereed)
    Abstract [en]

    The sulphated cholecystokinin (CCK) octapeptide (CCK-8S), the CCK tetrapeptide (CCK-4), neuropeptide Y (NPY) and γ-aminobutyric acid (GABA) were determined in cerebrospinal fluid (CSF) obtained from 11 pathological male gamblers and 11 healthy male controls. Compared with healthy controls, pathological male gamblers displayed higher concentrations of CCK-8S, CCK-4 and GABA (but not NPY). A gradient with decreasing concentrations from the first to the third 6-ml CSF fraction was found for CCK-8S, CCK-4 and NPY, but only in pathological gamblers. Disrupted gradients were found for GABA and for NPY in healthy controls. Given that CCK is a modulator of dopamine in the reward process, the increase in CCK-8S and CCK-4 is not unexpected. The high level of GABA in pathological gamblers is in conformity with a compensatory inhibitory action on noradrenergic neurons. The CSF gradient of CCK-8S and CCK-4 in pathological male gamblers (but not healthy controls) might indicate a difference in diurnal variation. The results obtained are in line with an altered CCK and GABA function in pathological gambling. © 2006 Springer-Verlag.

  • 11.
    Nordin, Conny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    CSF monoamine patterns in pathological gamblers and healthy controls2006In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 40, no 5, p. 454-459Article in journal (Refereed)
    Abstract [en]

    Previous reports on compounds in the cerebrospinal fluid (CSF) of pathological gamblers have focused on disturbed NA, DA and 5-HT function in the central nervous system. We have analysed precursors, transmitters and transmitter metabolites in 3 × 6 ml of CSF obtained from one female and 11 male pathological gamblers and 11 healthy male controls lumbar punctured at the L4-5 level after 8 h of fasting without preceding strict bedrest. Pathological gamblers displayed lower CSF levels of tryptophan and 5-HT while the opposite was the case for 5-HIAA, tyrosine, DA, HVA, DOPAC and HMPG. In contrast to previous studies, the NA level did not differ between pathological gamblers and healthy controls. A disrupted CSF gradient was noted for tryptophan, 5-HT, DA, HVA, DOPAC, NA and HMPG, but only in pathological gamblers. A disrupted gradient was found for 5-HIAA in both pathological gamblers and healthy controls. The results are in line with the presence of altered indoleamine and cathecholamine function in pathological gamblers as well as an altered CSF transport from the brain to the lumbar compartment in such gamblers. © 2005 Elsevier Ltd. All rights reserved.

  • 12.
    Nordin, Conny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Increased CSF homocysteine in pathological gamblers compared with healthy controls2009In: International Journal of Mental Health and Addiction, ISSN 1557-1874, E-ISSN 1557-1882, Vol. 7, no 1, p. 168-176Article in journal (Refereed)
    Abstract [en]

    Neurocognitive disturbances suggesting a frontal lobe dysfunction have been observed in pathological gamblers and alcohol dependents. Given that a high homocysteine level has been suggested to be a mediating factor in alcohol-related cognitive decline, we have determined homocysteine and cobalamine in cerebrospinal fluid (CSF) obtained from 11 pathological male gamblers and 11 healthy male controls. Compared with healthy controls, pathological gamblers displayed higher CSF levels of homocysteine while the opposite was the case with CSF cobalamine. Smoking decreased the levels of homocysteine while the concentrations of cobalamine were increased. Homocysteine is a sulphur-containing amino acid exerting cytotoxic effects in living cells. The metabolism of homocysteine to methionine is mediated by cobalamine and folate. Human studies suggest that homocysteine plays a role in brain damage and cognitive and memory decline. The relationship between pathological gambling, homocysteine, cobalamine, folate (not determined in the study) and cognitive processing warrants further investigation.

  • 13.
    Nordin, Conny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Letter: Altered CSF taurine function in pathological gambling2006In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 40, no 5, p. 473-474Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 14.
    Nordin, Conny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Letter: Reduced free tri-iodothyronine serum levels are lower in pathological male gamblers than in healthy male controls2005In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 39, no 4, p. 449-Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 15.
    Ohrt, T
    et al.
    Fac Hlth Sci, Dept Neurosci & Locomot Psychiat, SE-58185 Linkoping, Sweden.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Thorell, Lars-Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Cognitive distortions in panic disorder and major depression: Specificity for depressed mood1999In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 53, no 6, p. 459-464Article in journal (Refereed)
    Abstract [en]

    The Dysfunctional Attitude Scale (DAS) and the Automatic Thought Questionnaire (ATQ) are two widely used instruments in research on cognitive distortion in psychopathology. To investigate the specificity of the DAS and the ATQ for major depression and for depressive symptoms in panic disorder, 23 patients with panic disorder were examined with the DAS and the ATQ before and after an 8-week treatment period. Patients from a previous study on cognitive distortion in major depression were used for comparison of pretreatment ratings. The results support the hypothesis of specificity of cognitive distortions of type dysfunctional attitudes in accordance with the DAS and negative spontaneous thoughts in accordance with the ATQ for major depression and a sensitivity of negative spontaneous thoughts to absolute and relative levels of mild depressive symptoms in patients with panic disorder.

  • 16.
    Rousseau, Andreas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    ABC om Konfusion på somatisk vårdavdelning2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, p. 2270-2274Article in journal (Other academic)
  • 17.
    Shlik, J
    et al.
    Univ Tartu, EE-50090 Tartu, Estonia Linkoping Univ, Linkoping, Sweden.
    Nordin, Conny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Gunnarsson, Tove
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Maron, E
    Univ Tartu, EE-50090 Tartu, Estonia Linkoping Univ, Linkoping, Sweden.
    Toru, I
    Univ Tartu, EE-50090 Tartu, Estonia Linkoping Univ, Linkoping, Sweden.
    Cholecystokinin-serotonin interactions2002In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 17, p. 50S-51SConference paper (Other academic)
  • 18.
    Sjödin, Ingemar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Kutcher, S.P.
    Canada.
    Ravindran, A
    Canada.
    Burt, T
    USA.
    Efficacy of sertraline in improving quality of life and functioning in generalized anxiety disorder (GAD)2003In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 13, p. 365-366Article in journal (Other (popular science, discussion, etc.))
  • 19.
    Skogh, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Dahl, Marja-Liisa
    University Uppsala Hospital.
    High Correlation Between Serum and Cerebrospinal Fluid Olanzapine Concentrations in Patients With Schizophrenia or Schizoaffective Disorder Medicating With Oral Olanzapine as the Only Antipsychotic Drug2011In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 31, no 1, p. 4-9Article in journal (Refereed)
    Abstract [en]

    The primary aim of the present study was to investigate the relationship between steady state serum and cerebrospinal fluid (CSF) concentrations of olanzapine (OLA) and its metabolite 4-N-desmethylolanzapine (DMO) in patients with schizophrenia or schizoaffective disorder treated with oral OLA as the only antipsychotic drug. The influence of smoking, gender, age, as well as polymorphisms in cytochrome P450 CYP2D6, CYP1A2, and ABCB1 genes on the serum and CSF drug levels was also analyzed. Thirty-seven white outpatients (10 smokers and 27 nonsmokers) were included. From 29 of them, CSF was collected successfully. A strong correlation (Spearman rank correlation [r(s)] = 0.93; P = 0.05) was found between serum and CSF concentrations of OLA and a somewhat weaker correlation (r(s) = 0.5; P = 0.05) between those of DMO. The CSF concentrations of OLA and DMO were on average 12% and 16% of those in serum. Extensive metabolizers of CYP2D6 had higher (P = 0.05) daily doses than poor metabolizers when the influence of smoking was taken into account. Smokers had lower (P = 0.01) concentration-to-dose ratios of OLA in serum (mean, 2.23 ng/mL per mg vs 3.32 ng/mL per mg) and CSF (0.27 ng/mL per mg vs 0.41 ng/mL per mg) than nonsmokers. The concentration-to-dose ratio for serum DMO decreased with increasing age (r(s) = -0.41; P = 0.05). Carriers of ABCB1 1236T/2677T/3435T haplotype had higher serum (mean, 37.7 ng/mL vs 22.5 ng/mL; P = 0.035) and CSF (4.7 ng/mL vs 2.6 ng/mL; P = 0.018) OLA concentrations than patients without this haplotype. The present study shows a strong correlation between serum and CSF concentrations of OLA, indicating that concentrations of OLA in serum reflect those in CSF.

  • 20.
    Skogh, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Josefsson, Martin
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Dahl, M.L.
    Karolinska University Hospital, Department of Clinical Pharmacology, Stockholm, Sweden.
    Olanzapine in serum and cerebrospinal fluid in patients with schizophrenia or schizoaffective disorder2010In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 20, no Suppl. 3, p. S469-S469Article in journal (Other academic)
    Abstract [en]

    Background:  The relationship  between serum and CSF concentrations  of olanzapine  (OLA)  in humans  has  to our  knowledge not been described earlier. Few studies have investigated how the CYP2D6 and CYP1A2 polymorphisms affect OLA pharmacoki- netics in humans [1] [2]. Polymorphisms in the ABCB1 gene have been associated with altered pharmacokinetics of certain drugs including risperidone [3].The aim of the present study was to investigate the relationship between steady state serum and cerebrospinal fluid (CSF) con- centrations of OLA and its metabolite 4t -N-desmethylolanzapine (DMO) and to address the influence  of smoking,  gender, age as well as polymorphisms in genes coding for OLA metabolism (CYP2D6, CYP1A2) and transport (ABCB1) in patients with schizophrenia  or schizoaffective  disorder, treated with oral OLAas the only antipsychotic  drug.

    Methods: Thirty seven Caucasian outpatients (10 smokers and27 non-smokers),  suffering from schizophrenia or schizoaffective disorder according to DSM-IV criteria were included in the study. From 29 out of them, CSF was collected successfully.Fasting blood samples were collected in the morning for analy- ses of OLA and DMO and for genotyping (polymorphisms of CYP2D6,  CYP1A2  and  ABCB1).  Lumbar  puncture  was  per- formed  at close  connection  to blood  sampling  at the minimum of eight hours in the fasting state. The blood and CSF samples were stored at −70ºC until analysed.A validated accurate and sensitive LC-MS/MS method was used for the analysis of OLA and DMO. Analytes were quantified  by using linear gradient reversed phase chromatography with tandem mass  spectrometry  detection  operating  in  positive  electro-sprayionization mode with multiple reactions monitoring (MRM).

    Results:  A  strong  correlation  (rs =0.93;  p < 0.05)  was  foundbetween serum and CSF concentrations  of OLA and a somewhatweaker (rs =0.5; p < 0.05) between those of DMO. The CSF con- centrations  of  OLA  and  DMO  were  in  average  13%  and  16% of those in serum. Extensive metabolizers of CYP2D6 were pre- scribed higher (p < 0.05) daily doses than poor metabolizers when the influence of smoking habits was taken into account. Smokers had  lower  concentration-to-dose   ratios  (C/D)  of  OLA  both  in serum and CSF than non-smokers  (median  7 vs. 10 nmol/L/mg in serum and 0.8 vs. 1.3 nmol/L/mg  in CSF; p < 0.01). C/D for serum DMO decreased with increasing age (rs = −0.41; p < 0.05). Carriers of ABCB1 1236T/2677T/3435T haplotype had higher serum (median 112 vs. 80 nmol/L; p < 0.05) and CSF (13.7 vs. 8.1 nmol/L; p < 0.05) OLA concentrations  than patients without this haplotype. Patients treated with benzodiazepines and/or zopiclone (n = 8) had higher DMO and DMO/OLA ratio (p < 0.05 for both) in CSF compared to patients not co-medicating  with these drugs (n = 21), even when smoking habits were taken into account.

    Conclusion:  The present study shows a very good correlation between  serum and CSF concentrations  of OLA, indicating  thatconcentrations  of OLA in serum reflect the situation in CSF.

    References

    [1]  Hägg S, Spigset O, Lakso H, et al. Olanzapine disposition in humans is unrelated to CYP1A2 and CYP2D6 phenotypes. Eur J Clin Pharmacol2001;57:493−97.

    [2]  Carrillo  JA, Herra´iz  AG, Ramos SI, et al. Role of smoking-inducedcytochrome P450 (CYP)1A2 and polymorphic CYP2D6 in steady-stateconcentration of olanzapine. J Clin Psychopharmacol 2003;23:119−27.

    [3]  Gunes A, Spina E, Dahl M-L, et al. ABCB1 polymorphisms influencesteady-state  plasma  levels  of  9-hydroxyrisperidone   and  risperidoneactive moiety. Ther Drug Monit 2008;30:628−33.

  • 21.
    Wålinder, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Prochazka, J
    Odén, A
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Dahl, ML
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Mirtazapine naturalistic depression study (in Sweden) - MINDS(S): Clinical efficacy and safety2006In: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 21, no 3, p. 151-158Article in journal (Refereed)
    Abstract [en]

    Objective: To study how implementation of a naturalistic trial design for mirtazapine treatment in major depressive disorder for six (up to 12) months could be used and evaluated by means of clinical efficacy and safety. Method: An open-labelled, prospective, multicenter, non-comparative trial was conducted during a 2-year period in patients with major depression according to DSM-IV treated in psychiatric departments and primary care in Sweden. Minimal inclusion and exclusion criteria were used in order to diminish the potential patient selection bias. Maximum flexibility of the dosage of mirtazapine was allowed, and clinical assessments included MADRS, CGI, vital signs and spontaneous reporting of adverse events. Results: 192 patients were found eligible and enrolled in the study. A significant improvement in depressive symptoms according to MADRS and CGI was observed including particularly marked sleep improvement early in the treatment. Slight increases in body weight and BMI were observed. The investigational drug was well tolerated overall. Conclusion: The clinical efficacy and safety of mirtazapine found in this naturalistic setting is in line with previously reported data on mirtazapine in traditional controlled clinical trials. The results confirm that the naturalistic study design facilitated conduct of the trial. The authors suggest that this type of study design should also be applied to other antidepressant drugs that are frequently prescribed in the general population. Copyright © 2006 John Wiley & Sons, Ltd.

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