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Sjödin, Ingemar
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Hansson, C., Annerbrink, K., Nilsson, S., Bah, J., Olsson, M., Allgulander, C., . . . Dickson, S. L. (2013). A possible association between panic disorder and a polymorphism in the preproghrelin gene. Psychiatry Research, 206(1), 22-25
Open this publication in new window or tab >>A possible association between panic disorder and a polymorphism in the preproghrelin gene
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2013 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 206, no 1, p. 22-25Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Ghrelin, Obestatin, SNP, Anxiety, rs4684677, Gln90Leu, Panic disorder
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-93863 (URN)10.1016/j.psychres.2012.09.051 (DOI)000317442900004 ()
Note

Funding Agencies|Swedish Research Council for Medicine|2009-S266|European Commission|FP7-HEALTH-2009-241592FP7-KBBE-2009-3-245009FP7-KBBE-2010-4-266408|FOU/ALF Goteborg|ALFGBG-138741|Swedish Foundation for Strategic Research|A305-188|

Available from: 2013-06-11 Created: 2013-06-11 Last updated: 2017-12-06
Annerbrink, K., Hansson, C., Allgulander, C., Andersch, S., Sjödin, I., Holm, G., . . . Eriksson, E. (2011). A possible association between panic disorder and the ghrelin gene in EUROPEAN NEUROPSYCHOPHARMACOLOGY, vol 21, issue , pp S238-S238. In: EUROPEAN NEUROPSYCHOPHARMACOLOGY (pp. S238-S238). Elsevier, 21
Open this publication in new window or tab >>A possible association between panic disorder and the ghrelin gene in EUROPEAN NEUROPSYCHOPHARMACOLOGY, vol 21, issue , pp S238-S238
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2011 (English)In: EUROPEAN NEUROPSYCHOPHARMACOLOGY, Elsevier , 2011, Vol. 21, p. S238-S238Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-73356 (URN)000297383600135 ()
Available from: 2012-01-02 Created: 2012-01-02 Last updated: 2012-01-02
Skogh, E., Sjödin, I., Josefsson, M. & Dahl, M.-L. (2011). High Correlation Between Serum and Cerebrospinal Fluid Olanzapine Concentrations in Patients With Schizophrenia or Schizoaffective Disorder Medicating With Oral Olanzapine as the Only Antipsychotic Drug. Journal of Clinical Psychopharmacology, 31(1), 4-9
Open this publication in new window or tab >>High Correlation Between Serum and Cerebrospinal Fluid Olanzapine Concentrations in Patients With Schizophrenia or Schizoaffective Disorder Medicating With Oral Olanzapine as the Only Antipsychotic Drug
2011 (English)In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 31, no 1, p. 4-9Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Williams and Wilkins, 2011
Keywords
olanzapine, smoking, serum concentration, cerebrospinal fluid, pharmacogenetics
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-64762 (URN)10.1097/JCP.0b013e318204d9e2 (DOI)000285771000002 ()
Available from: 2011-02-04 Created: 2011-02-04 Last updated: 2017-12-11Bibliographically approved
Annerbrink, K., Westberg, L., Olsson, M., Andersch, S., Sjödin, I., Holm, G., . . . Eriksson, E. (2011). Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene. PSYCHIATRIC GENETICS, 21(2), 85-89
Open this publication in new window or tab >>Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene
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2011 (English)In: PSYCHIATRIC GENETICS, ISSN 0955-8829, Vol. 21, no 2, p. 85-89Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Rapid Communications of Oxford Ltd, 2011
Keywords
association study, orexin/hypocretin, panic disorder, polymorphism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-66853 (URN)10.1097/YPG.0b013e328341a3db (DOI)000287841700004 ()
Available from: 2011-03-22 Created: 2011-03-21 Last updated: 2011-03-22
Annerbrink, K., Westberg, L., Olsson, M., Allgulander, C., Andersch, S., Sjödin, I., . . . Eriksson, E. (2010). Association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder: A replication. Psychiatry Research, 178(1), 196-198
Open this publication in new window or tab >>Association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder: A replication
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2010 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 178, no 1, p. 196-198Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
Keywords
Psychiatric genetics; Association study; Catecholamines; Anxiety
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58254 (URN)10.1016/j.psychres.2009.11.022 (DOI)000279489400036 ()
Available from: 2010-08-10 Created: 2010-08-09 Last updated: 2017-12-12
Skogh, E., Sjödin, I., Josefsson, M. & Dahl, M. (2010). Olanzapine in serum and cerebrospinal fluid in patients with schizophrenia or schizoaffective disorder. Paper presented at The 23rd ECNP Congress, Amsterdam, the Netherlands, 28 August–1 September 2010. European Neuropsychopharmacology, 20(Suppl. 3), S469-S469
Open this publication in new window or tab >>Olanzapine in serum and cerebrospinal fluid in patients with schizophrenia or schizoaffective disorder
2010 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 20, no Suppl. 3, p. S469-S469Article in journal, Meeting abstract (Other academic) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2010
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-63947 (URN)10.1016/S0924-977X(10)70690-8 (DOI)000283687800577 ()
Conference
The 23rd ECNP Congress, Amsterdam, the Netherlands, 28 August–1 September 2010
Available from: 2011-01-10 Created: 2011-01-10 Last updated: 2017-12-11Bibliographically approved
Nordin, C. & Sjödin, I. (2009). Increased CSF homocysteine in pathological gamblers compared with healthy controls. International Journal of Mental Health and Addiction, 7(1), 168-176
Open this publication in new window or tab >>Increased CSF homocysteine in pathological gamblers compared with healthy controls
2009 (English)In: International Journal of Mental Health and Addiction, ISSN 1557-1874, E-ISSN 1557-1882, Vol. 7, no 1, p. 168-176Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer, 2009
Keywords
Cobalamine; CSF; Homocysteine; Pathological gambling
National Category
Substance Abuse
Identifiers
urn:nbn:se:liu:diva-18856 (URN)10.1007/s11469-008-9172-2 (DOI)
Available from: 2009-06-05 Created: 2009-06-05 Last updated: 2017-12-13Bibliographically approved
Henningsson, S., Annerbrink, K., Olsson, M., Allgulander, C., Andersch, S., Sjödin, I., . . . Westberg, L. (2007). Absence of the Arg441His polymorphism in the tryptophan hydroxylase 2 gene in adults with anxiety disorders and depression. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 144(6)
Open this publication in new window or tab >>Absence of the Arg441His polymorphism in the tryptophan hydroxylase 2 gene in adults with anxiety disorders and depression
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2007 (English)In: 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]

Publisher
p. 816-817
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-48666 (URN)10.1002/ajmg.b.30424 (DOI)
Available from: 2009-10-11 Created: 2009-10-11
Nordin, C., Gupta, R. & Sjödin, I. (2007). Cerebrospinal fluid amino acids in pathological gamblers and healthy controls. Neuropsychobiology, 56( 2-3), 152-158
Open this publication in new window or tab >>Cerebrospinal fluid amino acids in pathological gamblers and healthy controls
2007 (English)In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 56, no 2-3, p. 152-158Article in journal (Refereed) Published
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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-41713 (URN)10.1159/000115782 (DOI)58820 (Local ID)58820 (Archive number)58820 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Nordin, C. & Sjödin, I. (2007). CSF cholecystokinin, γ-aminobutyric acid and neuropeptide Y in pathological gamblers and healthy controls. Journal of neural transmission, 114(4), 499-503
Open this publication in new window or tab >>CSF cholecystokinin, γ-aminobutyric acid and neuropeptide Y in pathological gamblers and healthy controls
2007 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 114, no 4, p. 499-503Article in journal (Refereed) Published
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.

Keywords
Pathological gambling, CSF, cholecystokinin, NPY, GABA
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-37782 (URN)10.1007/s00702-006-0593-4 (DOI)38545 (Local ID)38545 (Archive number)38545 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
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