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  • 101. Celiker, Shemal
    et al.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wilhelmsson, Bo
    A radiofrequency vs topical steroid treatment of chronic nasal obstruction: A prospective randomized study of 84 cases2011In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 131, no 1, p. 79-83Article in journal (Refereed)
    Abstract [en]

    Conclusions:

    Nasal congestion caused by mucosal swelling and conch hypertrophy impairs breathing and causes snoring and headaches. Treatment of conch hypertrophy with radiofrequency (RF) allows reduction of mucosal swelling, minimization of hyperplasia, and decreased mucus production. This treatment provides a clinically significant improvement in snoring, headaches, and mouth breathing.

    Objective:

    To compare the efficacy of RF surgery to nasal steroid; each method used separately and both in combination.

    Methods:

    This was a consecutive randomized study, which included 84 patients with 3 outpatient visits, where the first visit included a complete medical history, assessment of ENT status, and skin tests. Nasal flow measured with rhinomanometry was done at the first visit and then before and after each treatment. Patients were asked to respond to a questionnaire at the first visit and after each subsequent treatment. Thereafter the variables were analyzed with established statistical methods.

    Results:

    Measurement of variables and patient questionnaire responses showed a clear improvement in several symptoms, such as sneezing and headache, and a clinically significant improvement in nasal congestion and snoring.

  • 102.
    Chabok, Abbas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Colonic Diverticulitis: Diagnostic and Therapeutic Aspects2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aims of this thesis were to evaluate diagnostic and therapeutic aspects of colonic diverticulitis.

    In the first study, a systematic review of the literature was performed to evaluate radiological diagnostics for patients with acute left-sided diverticulitis. Forty-nine relevant articles were found and read in full and data were extracted or calculated. Twenty-nine of these were excluded. The best evidence for the diagnosis of diverticulitis in the literature was to be found with US. Only one small study of good quality was found for both CT and MRI.

    In the second paper, a prospective multicentre study was performed to determine the faecal carriage of antibiotic-resistant bacteria and antibiotic treatment in 208 surgical patients with acute intra-abdominal infections. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL- and AmpC producing Enterobacteriaceae were found in samples from 13 patients (6.3%).  We found high rates of resistance among Enterobacteriaceae against antibiotics which were commonly used in Sweden.

    In the third paper, a multicentre randomized study was performed to investigate the need of antibiotic treatment in acute uncomplicated diverticulitis. Six hundred and twenty-three patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics. Complications were found in six patients (1.9%) in the no antibiotic and three (1.0%) in the antibiotic group (p=0.302). The median hospital stay was three days in both groups. Recurrent diverticulitis follow-up was similar in both groups (16%, p=0.895). We conclude that antibiotic treatment for acute uncomplicated diverticulitis neither accelerated recovery nor prevented complications or recurrence. Based on the results, antibiotics should therefore be reserved mainly for the treatment of complicated diverticulitis.

    The fourth paper presents a prospective observational study performed in two centres to evaluate CT colonography in the follow-up of acute diverticulitis as regards patient acceptance and diagnostic accuracy in 108 patients. Patients experienced colonoscopy as more painful (p<0.001) and uncomfortable (p<0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a level of relatively good agreement (К= 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (К= 0.17). We concluded that CTC was less painful and unpleasant. CTC detected diverticulosis with good accuracy while the accuracy of detection of small polyps was poor. CTC could be an alternative, especially in cases of incomplete colonoscopy or in a situation with limited colonoscopy resources.

    List of papers
    1. Acute colonic diverticulitis: a systematic review of diagnostic accuracy
    Open this publication in new window or tab >>Acute colonic diverticulitis: a systematic review of diagnostic accuracy
    Show others...
    2007 (English)In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 9, no 6, p. 480-488Article, review/survey (Refereed) Published
    Abstract [en]

    Objective To appraise the literature on the diagnosis of acute colonic diverticulitis by ultrasound (US), computed tomography (CT), barium enema (BE) and magnetic resonance imaging (MRI).

    Method The databases of Pub Med, the Cochrane Library and EMBASE were searched for articles on the diagnosis of diverticulitis published up to November 2005. Studies where US, CT, BE, or MRI were compared with a reference standard on consecutive or randomly selected patients were included. Three examiners independently read the articles according to a prespecified protocol. In case of disagreement consensus was sought. The level of evidence of each article was classified according to the criteria of the Centre for Evidence-Based Medicine (CEBM), Oxford, UK.

    Results Forty-nine articles relevant to the subject were found and read in full. Twenty-nine of these were excluded. Among the remaining 20 articles, only one study, evaluating both US and CT reached level of evidence 1b according to the CEBM criteria. Two US studies and one MRI study reached level 2b. The remaining studies were level 4.

    Conclusion The best evidence for diagnosis of diverticulitis in the literature is on US. Only one small study of good quality was found for CT and for MRI-colonoscopy.

    Keywords
    Acute Disease, Barium Sulfate/diagnostic use, Diverticulitis; Colonic/*diagnosis/radiography/ultrasonography, Enema, Humans, Magnetic Resonance Imaging, Sensitivity and Specificity, Tomography; X-Ray Computed
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-16030 (URN)10.1111/j.1463-1318.2007.01238.x (DOI)17573739 (PubMedID)
    Available from: 2008-04-08 Created: 2008-04-08 Last updated: 2017-12-08Bibliographically approved
    2. Prevalence of fecal carriage of antibiotic-resistant bacteria in patients with acute surgical abdominal infections
    Open this publication in new window or tab >>Prevalence of fecal carriage of antibiotic-resistant bacteria in patients with acute surgical abdominal infections
    Show others...
    2010 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 10, p. 1203-1210Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE:

    Antibiotic resistance is increasing worldwide. The aims of the current study were to determine the fecal carriage of antibiotic-resistant bacteria and antibiotic treatment in surgical patients admitted to hospital due to acute intra-abdominal infections.

    MATERIALS AND METHODS:

    Eight Swedish surgical units participated in this prospective multicenter investigation. Rectal swabs were obtained on admission to hospital. Cultures were performed on chromogenic agar and antibiotic susceptibility testing was performed using the disk diffusion method. Extended-spectrum beta-lactamase (ESBL)-phenotype was confirmed by Etest.

    RESULTS:

    Rectal samples were obtained and analyzed from 208 patients with intra-abdominal surgical infections. Surgery was performed in 134 patients (65%). Cephalosporins were the most frequently used empirical antibiotic therapy. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL-producing Enterobacteriaceae were found in samples from 10 patients (5%). Three patients had five E. coli isolates producing AmpC enzymes.

    CONCLUSIONS:

    This study shows a high rate of resistance among Enterobacteriaceae against antibiotics which are commonly used in Sweden and should have implications for the future choice of antibiotics for surgical patients.

    Keywords
    Abdominal infection, antibiotics, antibiotic resistance, bacteria, resistance
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-133102 (URN)10.3109/00365521.2010.495417 (DOI)000282151500010 ()20521871 (PubMedID)
    Available from: 2010-11-02 Created: 2010-11-02 Last updated: 2017-12-12Bibliographically approved
    3. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis
    Open this publication in new window or tab >>Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis
    Show others...
    2012 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 4, p. 532-539Article in journal (Refereed) Published
    Abstract [en]

    Background: The standard of care for acute uncomplicated diverticulitis today is antibiotic treatment, although there are no controlled studies supporting this management. The aim was to investigate the need for antibiotic treatment in acute uncomplicated diverticulitis, with the endpoint of recovery without complications after 12 months of follow-up.

    Methods: This multicentre randomized trial involving ten surgical departments in Sweden and one in Iceland recruited 623 patients with computed tomography-verified acute uncomplicated left-sided diverticulitis. Patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics.

    Results: Age, sex, body mass index, co-morbidities, body temperature, white blood cell count and C-reactive protein level on admission were similar in the two groups. Complications such as perforation or abscess formation were found in six patients (1.9 per cent) who received no antibiotics and in three (1.0 per cent) who were treated with antibiotics (P = 0.302). The median hospital stay was 3 days in both groups. Recurrent diverticulitis necessitating readmission to hospital at the 1-year follow-up was similar in the two groups (16 per cent, P = 0.881).

    Conclusion: Antibiotic treatment for acute uncomplicated diverticulitis neither accelerates recovery nor prevents complications or recurrence. It should be reserved for the treatment of complicated diverticulitis.

    Keywords
    Colonic Diverticulitis
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-167955 (URN)10.1002/bjs.8688 (DOI)000303150400013 ()22290281 (PubMedID)
    Conference
    5th Annual Scientific Meeting of the European-Society-of-Coloproctology, 24 september 2010, Sorrento Italy
    Available from: 2012-02-07 Created: 2012-02-02 Last updated: 2017-12-08Bibliographically approved
    4. CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy
    Open this publication in new window or tab >>CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy
    Show others...
    2013 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 979-986Article in journal (Refereed) Published
    Abstract [en]

    Objective. The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard. Methods. A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner. Results. Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 mm for both methods. The mean time for CTC evaluation was 20 mm. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (kappa = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (kappa = 0.17). No cancer was found. Conclusion. CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

    Keywords
    colonic diverticulitis, CT- colonography, colonoscopy, accuracy, sensitivity, specificity
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-168281 (URN)10.3109/00365521.2013.809597 (DOI)000322850500012 ()
    Available from: 2012-02-07 Created: 2012-02-07 Last updated: 2017-12-08Bibliographically approved
  • 103.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Andreasson, Kalle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nikberg, Maziar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Low risk of complications in patients with first-time acute uncomplicated diverticulitis2017In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 32, no 12, p. 1699-1702Article in journal (Refereed)
    Abstract [en]

    First-time acute uncomplicated diverticulitis (AUD) has been considered to have an increased risk of complication, but the level of evidence is low. The aim of the present study was to evaluate the risk of complications in patients with first-time AUD and in patients with a history of diverticulitis. This paper is a population-based retrospective study at Vastmanland's Hospital, VasterA<yen>s, Sweden, where all patients were identified with a diagnosis of colonic diverticular disease ICD-10 K57.0-9 from January 2010 to December 2014. The records of all patients were surveyed and patients with a computed tomography (CT)-verified AUD were included. Complications defined as CT-verified abscess, perforation, colonic obstruction, fistula, or sepsis within 1 month from the diagnosis of AUD were registered. Of 809 patients with AUD, 642 (79%) had first-time AUD and 167 (21%) had a previous history of AUD with no differences in demographic or clinical characteristics. In total, 16 (2%) patients developed a complication within 1 month irrespective of whether they had a previous history of diverticulitis (P = 0.345). In the binary logistic regression analysis, first-time diverticulitis was not associated with increased risk of complications (OR 1.58; CI 0.52-4.81). The rate of antibiotic therapy was about 7-10% during the time period and outpatient management increased from 7% in 2010 to 61% in 2014. The risk for development of complications is low in AUD with no difference between patients with first-time or recurrent diverticulitis. This result strengthens existing evidence on the benign disease course of AUD.

  • 104.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hjern, F.
    Haapaniemi, S.
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis2012In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 4, p. 532-539Article in journal (Refereed)
    Abstract [en]

    Background: The standard of care for acute uncomplicated diverticulitis today is antibiotic treatment, although there are no controlled studies supporting this management. The aim was to investigate the need for antibiotic treatment in acute uncomplicated diverticulitis, with the endpoint of recovery without complications after 12 months of follow-up.

    Methods: This multicentre randomized trial involving ten surgical departments in Sweden and one in Iceland recruited 623 patients with computed tomography-verified acute uncomplicated left-sided diverticulitis. Patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics.

    Results: Age, sex, body mass index, co-morbidities, body temperature, white blood cell count and C-reactive protein level on admission were similar in the two groups. Complications such as perforation or abscess formation were found in six patients (1.9 per cent) who received no antibiotics and in three (1.0 per cent) who were treated with antibiotics (P = 0.302). The median hospital stay was 3 days in both groups. Recurrent diverticulitis necessitating readmission to hospital at the 1-year follow-up was similar in the two groups (16 per cent, P = 0.881).

    Conclusion: Antibiotic treatment for acute uncomplicated diverticulitis neither accelerates recovery nor prevents complications or recurrence. It should be reserved for the treatment of complicated diverticulitis.

  • 105.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Smedh, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stenson, Marianne
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 979-986Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard. Methods. A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner. Results. Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 mm for both methods. The mean time for CTC evaluation was 20 mm. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (kappa = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (kappa = 0.17). No cancer was found. Conclusion. CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

  • 106.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Tärnberg, Maria
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nilsson, Lennart E
    Lindberg, Christian
    Hanberger, Håkan
    Prevalence of fecal carriage of antibiotic-resistant bacteria in patients with acute surgical abdominal infections2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 10, p. 1203-1210Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Antibiotic resistance is increasing worldwide. The aims of the current study were to determine the fecal carriage of antibiotic-resistant bacteria and antibiotic treatment in surgical patients admitted to hospital due to acute intra-abdominal infections.

    MATERIALS AND METHODS:

    Eight Swedish surgical units participated in this prospective multicenter investigation. Rectal swabs were obtained on admission to hospital. Cultures were performed on chromogenic agar and antibiotic susceptibility testing was performed using the disk diffusion method. Extended-spectrum beta-lactamase (ESBL)-phenotype was confirmed by Etest.

    RESULTS:

    Rectal samples were obtained and analyzed from 208 patients with intra-abdominal surgical infections. Surgery was performed in 134 patients (65%). Cephalosporins were the most frequently used empirical antibiotic therapy. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL-producing Enterobacteriaceae were found in samples from 10 patients (5%). Three patients had five E. coli isolates producing AmpC enzymes.

    CONCLUSIONS:

    This study shows a high rate of resistance among Enterobacteriaceae against antibiotics which are commonly used in Sweden and should have implications for the future choice of antibiotics for surgical patients.

  • 107.
    Checknita, Dave
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Univ Sjukhuset, Psychiat Bldg R5 00 C-O Jari Tiihonen, S-17176 Stockholm, Sweden.
    Ekström, Tomas J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Tiihonen, Jari
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hodgins, Sheilagh
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Univ Montreal, Inst Univ Sante Mentale Montreal, Montreal, PQ, Canada.
    Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women2018In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 125, no 7, p. 1053-1064Article in journal (Refereed)
    Abstract [en]

    Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In addition, PA and SA may alter gene activity through epigenetic mechanisms such as DNA methylation, thereby further modifying risk for disorders. We investigated whether methylation in a region spanning the MAOA first exon and part of the first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence, drug dependence, depression disorders, anxiety disorders, and conduct disorder. 114 Swedish women completed standardized diagnostic interviews and questionnaires to report PA and SA, and provided saliva samples for DNA extraction. DNA was genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of interest (chrX: 43,515,544-43,515,991) was measured. SA, not PA, was associated with hypermethylation of the MAOA first exon relative to no-abuse, and the association was robust to adjustment for psychoactive medication, alcohol and drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not their interaction, was associated with MAOA methylation. SA associated with all measured mental disorders. Hypermethylation of MAOA first exon mediated the association of SA with current depression, and both methylation levels and SA independently predicted lifetime depression. Much remains to be learned about the independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA first exon.

  • 108.
    Cloodt, Erika
    et al.
    Lund Univ, Dept Hlth Sci Lund, Div Physiotherapy, Lund, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rodby-Bousquet, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Lund Univ, Dept Clin Sci Lund, Orthopaed, Lund, Sweden..
    Demographic and modifiable factors associated with knee contracture in children with cerebral palsy2018In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 60, no 4, p. 391-396Article in journal (Refereed)
    Abstract [en]

    AimTo identify the prevalence of knee contracture and its association with gross motor function, age, sex, spasticity, and muscle length in children with cerebral palsy (CP). MethodCross-sectional data for passive knee extension were analysed in 3045 children with CP (1756 males, 1289 females; mean age 8y 1mo [SD 3.84]). CP was classified using the Gross Motor Function Classification System (GMFCS) levels I (n=1330), II (n=508), III (n=280), IV (n=449), and V (n=478). Pearson's chi(2) test and multiple binary logistic regression were applied to analyse the relationships between knee contracture and GMFCS level, sex, age, spasticity, hamstring length, and gastrocnemius length. ResultsKnee contracture greater than or equal to 5 degrees occurred in 685 children (22%). The prevalence of knee contracture was higher in older children and in those with higher GMFCS levels. Odds ratios (ORs) for knee contracture were significantly higher for children at GMFCS level V (OR=13.17), with short hamstring muscles (OR=9.86), and in the oldest age group, 13 years to 15 years (OR=6.80). InterpretationKnee contracture is associated with higher GMFCS level, older age, and shorter muscle length; spasticity has a small effect. Maintaining muscle length, especially of the hamstrings, is important for reducing the risk of knee contracture.

  • 109.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Berglund, Kenneth
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Why Do Adolescents Drink?: Motivational Patterns Related to Alcohol Consumption and Alcohol-Related Problems2010In: Substance Use & Misuse, ISSN 1082-6084, E-ISSN 1532-2491, Vol. 45, no 10, p. 1589-1604Article in journal (Refereed)
    Abstract [en]

    The present study was designed to investigate motivational patterns for drinking alcohol and their relation about alcohol consumption and problems related to alcohol consumption. Data were collected by semistructured interviews and questionnaires, containing questions about reasons for drinking, alcohol consumption, and problems related to alcohol consumption during the years 2001, 2004, and 2005. Three independent population samples from two different counties of central Sweden were included. A total of 11,167 adolescents participated. Data on reasons for drinking were analyzed by factor analysis to extract components explaining drinking motives. Relationships between motivational patterns and alcohol use were examined with correlation analysis. Three drinking motives emerged (social-enhancement, coping, and dominance motives) and related to alcohol consumption and problems related to alcohol consumption. Limitations of the study are noted and discussed.

  • 110.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Göktürk, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hallman, Jarmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    The clock gene PER2 and sleep problems: association with alcohol consumption among Swedish adolescents2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Alcohol abuse is associated with sleep problems, which are often linked to circadian rhythm disturbances. Previous studies have separately examined the effects of mutations in the clock gene PER2 on alcohol consumption and sleep problems. Here we hypothesized that an allelic variation in the PER2 gene is associated with alcohol consumption in interaction with sleep problems among adolescents. METHODS: The Survey of Adolescent Life and Health in Västmanland 2006, a Swedish county, including 1254 students 17-18 years old, was used as a population-representative sample of adolescents. We investigated the PER2 Single Nucleotide polymorphism (SNP) 10870 (A/G) in the cohort together with an assessment of alcohol consumption according to the AUDIT-C questionnaire, and sleep problems using a survey consisting of 18 items. Furthermore, we carried out an exploratory analysis on the PER2 Single Nucleotide Polymorphism 10870 polymorphism in a group of severely alcoholic females. RESULTS: We found a significant association of the SNP 10870 in adolescent boys, where the genotype AA, in the presence of several and frequent sleep problems, was associated with increased alcohol consumption. Among adolescent girls, only sleep problems were related to alcohol consumption. A non-significant trend was observed among the severely alcoholic females, with the G allele being over-represented in the severely alcoholic females group in comparision to the control females. CONCLUSION: These results indicate that PER2 gene variation is associated with alcohol consumption in interaction with sleep problems among Swedish adolescent boys.

  • 111.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kronstrand, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Alling, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Adolescent alcohol consumption: Biomarkers PEth and FAEE in relation to interview and questionnaire data2009In: Journal of Studies on Alcohol and Drugs, ISSN 1937-1888, E-ISSN 1938-4114, Vol. 70, no 5, p. 797-804Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

     The aim of this study was to investigate the congruence of biomarkers, questionnaires, and interviews as instruments to assess adolescent alcohol consumption.

    METHOD

     The methodology used was a cross-sectional study with a randomized sample. Four different methods were used to estimate high adolescent alcohol consumption. The concordance of the results was investigated. Surveys were performed, and biological specimens were collected at all schools in the county of Västmanland, Sweden, in 2001. Eighty-one boys and 119 girls from a population of 16- and 19-year-old adolescents were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behaviors. Using a questionnaire (for a 1-hour session) and in-depth interviews, subjects were assessed regarding their alcohol-use habits. Blood and hair samples were analyzed for phosphatidylethanol (PEth) and fatty acid ethyl esters (FAEEs), respectively.

    RESULTS

     High alcohol consumption was underreported in the questionnaire compared with the interviews. PEth and FAEE analyses weakly confirmed the self-reports, and the results of the two biochemical tests did not overlap. The PEth blood test was the most specific but the least sensitive, whereas the FAEE hair test revealed low specificity and an overrepresentation of positive results in girls.

    CONCLUSIONS

    The expected higher self-report of high alcohol consumption by interview rather than by questionnaire was confirmed partly because of the influence of a bogus pipeline procedure. The absence of overlap between PEth and FAEE results and their poor agreement with self-reports suggested that biomarkers are unsuitable as screening tools for alcohol consumption in adolescents.

  • 112.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Sylvén, Sara M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Postpartum depression symptoms: a case-control study on monoaminergic functional polymorphisms and environmental stressors2011In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 21, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Postpartum depression (PPD) is an under diagnosed and under treated mood disorder, with negative impact on both the mother and the infant's health. The aim of this study is to examine whether genetic variations in the monoaminergic neurotransmitter system, together with environmental stressors, contribute to the development of PPD symptoms.

    METHODS:

    This nested case-control study included 275 women from a population-based cohort of delivering women in Sweden. A questionnaire containing the Edinburgh Postnatal Depression Scale was collected at 6 weeks and 6 months postpartum. Three functional polymorphisms were genotyped, catechol-O-methyltransferase (COMT)-ValMet, monoamine oxidase A (MAOA)-upstream variable number tandem repeat (uVNTR) and serotonin transporter linked polymorphic region (5HTT-LPR). Stressful life events, maternity stressors and previous psychiatric contact were considered as potential risk factors.

    RESULTS:

    COMT-ValMet was significantly associated with PPD symptoms at 6 weeks, but not at 6 months postpartum. A significant gene-gene interaction effect was present between COMT-ValMet and MAOA-uVNTR. In a gene-environment multivariate model, COMT-ValMet, psychiatric contact and maternity stressors were significantly associated with PPD symptoms. Among those with history of psychiatric problems, the COMT-ValMet and 5HTT-LPR risk variants were associated with PPD symptoms, whereas in the absence of previous psychiatric contact only maternity stressors were related to PPD symptoms.

    CONCLUSION:

    The interaction effect between monoaminergic genes and environmental stressors is likely to contribute to vulnerability for PPD. The different patterns of association according to history of psychiatric problems, if replicated, might be helpful in screening strategies.

  • 113.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Alpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats2015In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 12, no 7, p. 7154-7171Article in journal (Refereed)
    Abstract [en]

    Stressful events early in life, later high alcohol consumption and vulnerability to alcohol use disorder (AUD) are tightly linked. Norepinephrine is highly involved in the stress response and the alpha 2A-adrenoceptor, which is an important regulator of norepinephrine signalling, is a putative target in pharmacotherapy of AUD. The aim of the present study was to investigate the effects of early-life stress and adult voluntary alcohol drinking on the alpha 2A-adrenoceptor. The relative expression and promoter DNA methylation of the Adra2a gene were measured in the hypothalamus, a key brain region in stress regulation. A well-characterized animal model of early-life stress was used in combination with an episodic voluntary drinking in adulthood. Alcohol drinking rats with a history of early-life stress had lower Adra2a expression than drinking rats not exposed to stress. Alcohol intake and Adra2a gene expression were negatively correlated in high-drinking animals, which were predominantly rats subjected to early-life stress. The results provide support for a link between early-life stress, susceptibility for high alcohol consumption, and low Adra2a expression in the hypothalamus. These findings can increase our understanding of the neurobiological basis for vulnerability to initiate risk alcohol consumption and individual differences in the response to 2A-adrenoceptor agonists.

  • 114.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Mujtaba, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    EXPERIMENTAL EVIDENCE OF A LINK BETWEEN THE alpha 2A-ADRENERGIC RECEPTOR GENE, EARLY LIFE STRESS, AND ETHANOL DRINKING2015In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50Article in journal (Other academic)
  • 115.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: A replication study2013In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 10, p. 1300-1306Article in journal (Refereed)
    Abstract [en]

    Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Västmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R2=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.

  • 116.
    Conden, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents2013In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 13, p. 11-Article in journal (Refereed)
    Abstract [en]

    Background: Type D personality, or the "distressed personality", is a psychosocial factor associated with negative health outcomes, although its impact in younger populations is unclear. The purpose of this study was to investigate the prevalence of Type D personality and the associations between Type D personality and psychosomatic symptoms and musculoskeletal pain among adolescences. Methods: A population-based, self-reported cross-sectional study conducted in Vastmanland, Sweden with a cohort of 5012 students in the age between 15-18 years old. The participants completed the anonymous questionnaire Survey of Adolescent Life in Vastmanland 2008 during class hour. Psychosomatic symptoms and musculoskeletal pain were measured through index measuring the presence of symptoms and how common they were. DS14 and its two component subscales of negative affectivity (NA) and social inhibition (SI) were measured as well. Results: There was a difference depending on sex, where 10.4% among boys and 14.6% among girls (p = < 0.001) were defined as Type D personality. Boys and girls with a Type D personality had an approximately 2-fold increased odds of musculoskeletal pain and a 5-fold increased odds of psychosomatic symptoms. The subscale NA explained most of the relationship between Type D personality and psychosomatic symptoms and musculoskeletal pain. No interaction effect of NA and SI was found. Conclusions: There was a strong association between Type D personality and both psychosomatic symptoms and musculoskeletal pain where adolescent with a type D personality reported more symptoms. The present study contributes to the mapping of the influence of Type D on psychosomatic symptoms and musculoskeletal pain among adolescents.

  • 117.
    Condén, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality and ill-health among Swedish adolescents2013Licentiate thesis, comprehensive summary (Other academic)
    List of papers
    1. Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents
    Open this publication in new window or tab >>Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents
    2013 (English)In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 13, p. 11-Article in journal (Refereed) Published
    Abstract [en]

    Background: Type D personality, or the "distressed personality", is a psychosocial factor associated with negative health outcomes, although its impact in younger populations is unclear. The purpose of this study was to investigate the prevalence of Type D personality and the associations between Type D personality and psychosomatic symptoms and musculoskeletal pain among adolescences. Methods: A population-based, self-reported cross-sectional study conducted in Vastmanland, Sweden with a cohort of 5012 students in the age between 15-18 years old. The participants completed the anonymous questionnaire Survey of Adolescent Life in Vastmanland 2008 during class hour. Psychosomatic symptoms and musculoskeletal pain were measured through index measuring the presence of symptoms and how common they were. DS14 and its two component subscales of negative affectivity (NA) and social inhibition (SI) were measured as well. Results: There was a difference depending on sex, where 10.4% among boys and 14.6% among girls (p = < 0.001) were defined as Type D personality. Boys and girls with a Type D personality had an approximately 2-fold increased odds of musculoskeletal pain and a 5-fold increased odds of psychosomatic symptoms. The subscale NA explained most of the relationship between Type D personality and psychosomatic symptoms and musculoskeletal pain. No interaction effect of NA and SI was found. Conclusions: There was a strong association between Type D personality and both psychosomatic symptoms and musculoskeletal pain where adolescent with a type D personality reported more symptoms. The present study contributes to the mapping of the influence of Type D on psychosomatic symptoms and musculoskeletal pain among adolescents.

    Keywords
    Adolescents, Musculoskeletal pain, Negative affectivity, Psychosomatic symptoms, Social inhibition, Type D personality
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-197125 (URN)10.1186/1471-2431-13-11 (DOI)000314838500001 ()
    Available from: 2013-03-19 Created: 2013-03-18 Last updated: 2017-12-06Bibliographically approved
    2. Type D personality is associated with sleep problems in adolescents. Results from a population-based cohort study of Swedish adolescents
    Open this publication in new window or tab >>Type D personality is associated with sleep problems in adolescents. Results from a population-based cohort study of Swedish adolescents
    2013 (English)In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 74, no 4, p. 290-295Article in journal (Refereed) Published
    Abstract [en]

    Objective: Sleep problems are associated with an increased risk of psychiatric and somatic diseases. Type D personality, or the distressed personality, refers to the joint tendency to experience negative emotions and to inhibit self-expression in social interaction. Type D personality is associated with an increased number of health complaints including cardiovascular diseases. The present study investigated whether Type D personality was associated with sleep problems among adolescents. Methods: The study was part of the Survey of Adolescent Life in Vastmanland 2008 (SALVe 2008). A total of 5012 adolescents (age 15-18 years old) completed a questionnaire including the Type D measurement DS14 and questions on sleep disturbances, sleep hours during school nights, and sleep hours during weekend nights. Results: Adolescents with a Type D personality had an approximately four times increased risk of having sleep disturbances. Moreover, Type D personality was associated with sleeping fewer hours. Conclusion: As adolescence represents a formative period for development it is critical to identify sleep disorders early. The presence of Type D personality associated with poor sleep demands attention because sleep problems may be an early stage in the development of later diseases.

    Keywords
    Adolescents, Sleep behaviours, Sleep disturbances, Sleep hours, Type D personality
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-198608 (URN)10.1016/j.jpsychores.2012.11.011 (DOI)000316586600004 ()
    Available from: 2013-04-22 Created: 2013-04-22 Last updated: 2017-12-06Bibliographically approved
  • 118.
    Condén, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D Personality: Psychometric Properties of the DS14 and Associations with Ill Health and Coronary Heart Disease in General and Clinical Populations2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type D personality, or distressed personality, refers to the joint tendency to experience negative emotions and to inhibit self-expression in social interactions. The overall aims of this thesis were to examine the impact of Type D personality on adolescents’ self-perceived health, to examine the factorial and temporal stability of the Type D personality construct DS14, and to clarify whether type D personality is an independent risk factor for recurrent myocardial infarction and all-cause mortality among patients with myocardial infarction.

    The prevalence of Type D personality in the adolescent population was 10.4% for boys and 14.6% for girls. Boys and girls with Type D personality were approximately twice as likely to report musculoskeletal pain and five times as likely to report psychosomatic symptoms.

    Adolescents with Type D personality were four times more likely to have sleep disturbances and to sleep fewer hours, especially on school nights.

    Among patients with myocardial infarction, the Swedish DS14 had stable structural validity. Our measurements confirmed the two-factor model of the DS14. However, the DS14 exhibited low temporal stability, especially when comparing the measurement obtained during hospitalization with the 1- and 12-month follow-up measurements.

    Among patients with myocardial infarction, the Framingham risk score had a strong predictive value for recurrent myocardial infarction, and a somewhat weaker predictive value for all-cause mortality. However, none of the previously proposed methods for the analysis of the DS14 Type D personality measurement predicted recurrent myocardial infarction or all-cause mortality, either in univariable analyses or in addition to the Framingham risk score.

    In conclusion, the present thesis found significant associations between the DS14 and psychosomatic symptoms in adolescents. However, the measurement exhibited a low stability over time and no predictive value for recurrent myocardial infarction and mortality among patients with myocardial infarction. Taken together, these results raise the question of whether the Swedish DS14 really is a measure of personality. An alternative explanation for the strong cross-sectional associations observed between the DS14 and psychosomatic symptoms might be that the DS14 functions as a pseudo-measure of ill health, or co-varies with depressive or psychosomatic characteristics.

    List of papers
    1. Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents
    Open this publication in new window or tab >>Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents
    2013 (English)In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 13, p. 11-Article in journal (Refereed) Published
    Abstract [en]

    Background: Type D personality, or the "distressed personality", is a psychosocial factor associated with negative health outcomes, although its impact in younger populations is unclear. The purpose of this study was to investigate the prevalence of Type D personality and the associations between Type D personality and psychosomatic symptoms and musculoskeletal pain among adolescences. Methods: A population-based, self-reported cross-sectional study conducted in Vastmanland, Sweden with a cohort of 5012 students in the age between 15-18 years old. The participants completed the anonymous questionnaire Survey of Adolescent Life in Vastmanland 2008 during class hour. Psychosomatic symptoms and musculoskeletal pain were measured through index measuring the presence of symptoms and how common they were. DS14 and its two component subscales of negative affectivity (NA) and social inhibition (SI) were measured as well. Results: There was a difference depending on sex, where 10.4% among boys and 14.6% among girls (p = < 0.001) were defined as Type D personality. Boys and girls with a Type D personality had an approximately 2-fold increased odds of musculoskeletal pain and a 5-fold increased odds of psychosomatic symptoms. The subscale NA explained most of the relationship between Type D personality and psychosomatic symptoms and musculoskeletal pain. No interaction effect of NA and SI was found. Conclusions: There was a strong association between Type D personality and both psychosomatic symptoms and musculoskeletal pain where adolescent with a type D personality reported more symptoms. The present study contributes to the mapping of the influence of Type D on psychosomatic symptoms and musculoskeletal pain among adolescents.

    Keywords
    Adolescents, Musculoskeletal pain, Negative affectivity, Psychosomatic symptoms, Social inhibition, Type D personality
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-197125 (URN)10.1186/1471-2431-13-11 (DOI)000314838500001 ()
    Available from: 2013-03-19 Created: 2013-03-18 Last updated: 2017-12-06Bibliographically approved
    2. Type D personality is associated with sleep problems in adolescents. Results from a population-based cohort study of Swedish adolescents
    Open this publication in new window or tab >>Type D personality is associated with sleep problems in adolescents. Results from a population-based cohort study of Swedish adolescents
    2013 (English)In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 74, no 4, p. 290-295Article in journal (Refereed) Published
    Abstract [en]

    Objective: Sleep problems are associated with an increased risk of psychiatric and somatic diseases. Type D personality, or the distressed personality, refers to the joint tendency to experience negative emotions and to inhibit self-expression in social interaction. Type D personality is associated with an increased number of health complaints including cardiovascular diseases. The present study investigated whether Type D personality was associated with sleep problems among adolescents. Methods: The study was part of the Survey of Adolescent Life in Vastmanland 2008 (SALVe 2008). A total of 5012 adolescents (age 15-18 years old) completed a questionnaire including the Type D measurement DS14 and questions on sleep disturbances, sleep hours during school nights, and sleep hours during weekend nights. Results: Adolescents with a Type D personality had an approximately four times increased risk of having sleep disturbances. Moreover, Type D personality was associated with sleeping fewer hours. Conclusion: As adolescence represents a formative period for development it is critical to identify sleep disorders early. The presence of Type D personality associated with poor sleep demands attention because sleep problems may be an early stage in the development of later diseases.

    Keywords
    Adolescents, Sleep behaviours, Sleep disturbances, Sleep hours, Type D personality
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-198608 (URN)10.1016/j.jpsychores.2012.11.011 (DOI)000316586600004 ()
    Available from: 2013-04-22 Created: 2013-04-22 Last updated: 2017-12-06Bibliographically approved
    3. Prevalence of Type D Personality and Factorial and Temporal Stability of the DS14 after Myocardial Infarction in a Swedish Population
    Open this publication in new window or tab >>Prevalence of Type D Personality and Factorial and Temporal Stability of the DS14 after Myocardial Infarction in a Swedish Population
    2014 (English)In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 55, no 6, p. 601-610Article in journal (Refereed) Published
    Abstract [en]

    This study examined the prevalence of Type D personality and the temporal stability, internal consistency, and construct validity of the DS14 at three time points after myocardial infarction. The prevalence of Type D personality was 14.0% during hospitalization, 25.1% at 1 month, and 19.2% at 12 months. A total of 6.1% of patients were classified as Type D personality at all three assessments, whereas 68.4% were stable non-Type D and 25.6% changed between personality classifications. The DS14 had stable structural validity, but low temporal stability over time, especially from hospitalization to the 1-month and 12-month follow-ups (k = 0.365 and 0.397, respectively).

    National Category
    Psychiatry
    Identifiers
    urn:nbn:se:uu:diva-232467 (URN)10.1111/sjop.12162 (DOI)000345219900012 ()25243796 (PubMedID)
    Available from: 2014-09-19 Created: 2014-09-18 Last updated: 2017-12-05Bibliographically approved
    4. Type D personality as an independent risk factor for recurrent myocardial infarction and all-cause mortality in addition to theFramingham risk score: a prospective cohort-study
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    2014 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754Article in journal (Refereed) Submitted
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-232533 (URN)
    Available from: 2014-09-19 Created: 2014-09-19 Last updated: 2017-12-05Bibliographically approved
  • 119.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality is associated with sleep problems in adolescents. Results from a population-based cohort study of Swedish adolescents2013In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 74, no 4, p. 290-295Article in journal (Refereed)
    Abstract [en]

    Objective: Sleep problems are associated with an increased risk of psychiatric and somatic diseases. Type D personality, or the distressed personality, refers to the joint tendency to experience negative emotions and to inhibit self-expression in social interaction. Type D personality is associated with an increased number of health complaints including cardiovascular diseases. The present study investigated whether Type D personality was associated with sleep problems among adolescents. Methods: The study was part of the Survey of Adolescent Life in Vastmanland 2008 (SALVe 2008). A total of 5012 adolescents (age 15-18 years old) completed a questionnaire including the Type D measurement DS14 and questions on sleep disturbances, sleep hours during school nights, and sleep hours during weekend nights. Results: Adolescents with a Type D personality had an approximately four times increased risk of having sleep disturbances. Moreover, Type D personality was associated with sleeping fewer hours. Conclusion: As adolescence represents a formative period for development it is critical to identify sleep disorders early. The presence of Type D personality associated with poor sleep demands attention because sleep problems may be an early stage in the development of later diseases.

  • 120.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Philippe, Wagner
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality as an independent risk factor for recurrent myocardial infarction and all-cause mortality in addition to theFramingham risk score: a prospective cohort-study2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754Article in journal (Refereed)
  • 121.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp Vasteras, Dept Med, Vasteras, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Insomnia predicts long-term all-cause mortality after acute myocardial infarction: A prospective cohort study2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 215, p. 217-222Article in journal (Refereed)
    Abstract [en]

    Background: Sleep impairment such as insomnia is an established risk factor for the development of cardiovascular disease and acute myocardial infarction (AMI). The aim of the current study was to examine the association between insomnia and all-cause mortality among AMI patients. Methods: This prospective cohort study used data on n = 732 patients recruited from September 2006 to May 2011 as part of the Vastmanland Myocardial Infarction Study (VaMIS), a prospective cohort study of AMI patients living in Vastmanland County, Sweden. Participants were followed up for all-cause mortality until December 9, 2015. The outcome of interest was time-to-death (TTD), with the presence of insomnia being the risk factor of main interest. Data were analyzed using a piecewise Cox regression model with change point for insomnia at two years of follow-up, adjusted for socioeconomic, lifestyle and clinical risk factors. Results: In total, n = 175 (23.9%) of the participants suffered from insomnia. During a mean (SD) follow-up time of 6.0 (2.5) years (4392 person-years), a total of n = 231 (31.6%) participants died, n = 77 (44.0%) in the insomnia group and n= 154 (27.6%) in the non-insomnia group (log-rank test p < 0.001). In a multiple adjusted piecewise Cox regression model, insomnia did not imply a higher risk of death during the first two years after AMI (HR 0.849; 95% CI 0.508-1.421; p = 0.534). During the period after the first two years, however, insomnia implied a 1.6 times higher risk of death (HR 1.597; 95% CI 1.090-2.341; p = 0.016). Conclusions: Insomnia implies a higher risk of death among AMI patients in the long term.

  • 122.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Prevalence of Type D Personality and Factorial and Temporal Stability of the DS14 after Myocardial Infarction in a Swedish Population2014In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 55, no 6, p. 601-610Article in journal (Refereed)
    Abstract [en]

    This study examined the prevalence of Type D personality and the temporal stability, internal consistency, and construct validity of the DS14 at three time points after myocardial infarction. The prevalence of Type D personality was 14.0% during hospitalization, 25.1% at 1 month, and 19.2% at 12 months. A total of 6.1% of patients were classified as Type D personality at all three assessments, whereas 68.4% were stable non-Type D and 25.6% changed between personality classifications. The DS14 had stable structural validity, but low temporal stability over time, especially from hospitalization to the 1-month and 12-month follow-ups (k = 0.365 and 0.397, respectively).

  • 123.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Malardalen Univ, Sch Hlth Care & Social Welf, Vasteras, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Is type D personality an independent risk factor for recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients?2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 5, p. 522-533Article in journal (Refereed)
    Abstract [en]

    Background: Type D personality refers to a combination of simultaneously high levels of negative affectivity and social inhibition. The present study aimed to examine whether type D personality was independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality. Design: This was a prospective cohort study. Methods: Utilising data from the Vastmanland Myocardial Infarction Study, 946 post-acute myocardial infarction patients having data on the DS14 instrument used to measure type D personality were followed-up for recurrent myocardial infarction and all-cause mortality until 9 December 2015. Data were analysed using Cox regression, adjusted for established risk factors. Results: In total, 133 (14.1%) patients suffered from type D personality. During a mean follow-up time for recurrent myocardial infarction of 5.7 (3.2) years, 166 (17.5%) patients were affected by recurrent myocardial infarction, of which 26 (15.7%) had type D personality, while during a mean follow-up time for all-cause mortality of 6.3 (2.9) years, 321 (33.9%) patients died, of which 42 (13.1%) had type D personality. After adjusting for established risk factors, type D personality was not significantly associated with recurrent myocardial infarction or all-cause mortality using any of the previously proposed methods for measuring type D personality. A weak association was found between the social inhibition part of type D personality and a decreased risk of all-cause mortality, but this association was not significant after taking missing data into account in a multiple imputation analysis. Conclusions: No support was found for type D personality being independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality.

  • 124.
    Culverhouse, R. C.
    et al.
    Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA..
    Saccone, N. L.
    Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Horton, A. C.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Ma, Y.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Anstey, K. J.
    Australian Natl Univ, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT, Australia..
    Banaschewski, T.
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany..
    Burmeister, M.
    Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Cohen-Woods, S.
    Flinders Univ S Australia, Sch Psychol, Fac Social & Behav Sci, Adelaide, SA, Australia..
    Etain, B.
    Univ Paris Diderot, Sorbonne Paris Cite, UMR S 1144, Paris, France.;AP HP, Grp St Louis Lariboisiere F, Paris, France.;INSERM, U1144, Paris, France..
    Fisher, H. L.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England..
    Goldman, N.
    Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA..
    Guillaume, S.
    Univ Montpellier, Montpellier, France.;INSERM, Neuropsychiat U1061, Montpellier, France.;CHU Montpellier, Dept Emergency Psychiat & Acute Care, Montpellier, France..
    Horwood, J.
    Univ Otago Christchurch, Dept Psychol Med, Christchurch, New Zealand..
    Juhasz, G.
    Semmelweis Univ, Hungarian Acad Sci, MTA SE NAP Genet Brain Imaging Migraine Res Grp B, Budapest, Hungary.;Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Univ Manchester, Neurosci & Psychiat Unit, Manchester, Lancs, England.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary..
    Lester, K. J.
    Univ Sussex, Sch Psychol, Brighton, E Sussex, England..
    Mandelli, L.
    Univ Bologna, Dept Biomed & NeuroMotor Sci, Bologna, Italy..
    Middeldorp, C. M.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Olie, E.
    Univ Montpellier, Montpellier, France.;INSERM, Neuropsychiat U1061, Montpellier, France.;CHU Montpellier, Dept Emergency Psychiat & Acute Care, Montpellier, France..
    Villafuerte, S.
    Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA..
    Air, T. M.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Araya, R.
    London Sch Hyg & Trop Med, Ctr Global Mental Hlth, London, England..
    Bowes, L.
    Univ Oxford, Dept Expt Psychol, Oxford, England..
    Burns, R.
    Australian Natl Univ, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT, Australia..
    Byrne, E. M.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Coffey, C.
    Murdoch Childrens Res Inst, Ctr Adolescent Hlth, Melbourne, Vic, Australia..
    Coventry, W. L.
    Univ New England, Discipline Psychol, Armidale, NSW, Australia..
    Gawronski, K. A. B.
    Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Glei, D.
    Georgetown Univ, Ctr Populat & Hlth, Washington, DC USA..
    Hatzimanolis, A.
    Univ Athens, Sch Med, Eginit Hosp, Dept Psychiat, Athens, Greece.;Theodor Theohari Cozzika Fdn, Neurobiol Res Inst, Athens, Greece..
    Hottenga, J-J
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Jaussent, I.
    INSERM, Neuropsychiat U1061, Montpellier, France..
    Jawahar, C.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Jennen-Steinmetz, C.
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Biostat, Mannheim, Germany..
    Kramer, J. R.
    Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA..
    Lajnef, M.
    INSERM, U955, Creteil, France..
    Little, K.
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia.;Univ Melbourne, Sch Psychol Sci, Melbourne, Vic, Australia..
    zu Schwabedissen, H. M.
    Univ Basel, Dept Pharmaceut Sci, Biopharm, Basel, Switzerland..
    Nauck, M.
    Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany..
    Nederhof, E.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Petschner, P.
    Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary.;Semmelweis Univ, Hungarian Acad Sci, MTA SE Neuropsychopharmacol & Neurochem Res Grp, Budapest, Hungary..
    Peyrot, W. J.
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;GGZ InGeest, Amsterdam, Netherlands..
    Schwahn, C.
    Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany..
    Sinnamon, G.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Stacey, D.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Tian, Y.
    Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA..
    Toben, C.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Van der Auwera, S.
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany..
    Wainwright, N.
    Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Wang, J-C
    Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA..
    Willemsen, G.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Anderson, I. M.
    Univ Manchester, Neurosci & Psychiat Unit, Manchester, Lancs, England.;Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England..
    Arolt, V.
    Univ Munster, Dept Psychiat & Psychotherapy, Munster, Germany..
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp Västerås, Västerås, Sweden..
    Bagdy, G.
    Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary.;Semmelweis Univ, Hungarian Acad Sci, MTA SE Neuropsychopharmacol & Neurochem Res Grp, Budapest, Hungary..
    Baune, B. T.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Bellivier, F.
    Univ Paris Diderot, Sorbonne Paris Cite, UMR S 1144, Paris, France.;AP HP, Grp St Louis Lariboisiere F, Paris, France.;INSERM, U1144, Paris, France..
    Boomsma, D. I.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Courtet, P.
    Univ Montpellier, Montpellier, France.;INSERM, Neuropsychiat U1061, Montpellier, France.;CHU Montpellier, Dept Emergency Psychiat & Acute Care, Montpellier, France..
    Dannlowski, U.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.;Univ Munster, Dept Psychiat & Psychotherapy, Munster, Germany..
    de Geus, E. J. C.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Deakin, J. F. W.
    Univ Manchester, Neurosci & Psychiat Unit, Manchester, Lancs, England.;Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England..
    Easteal, S.
    Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia..
    Eley, T.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Fergusson, D. M.
    Univ Otago Christchurch, Dept Psychol Med, Christchurch, New Zealand..
    Goate, A. M.
    Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA..
    Gonda, X.
    Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary.;Semmelweis Univ, Hungarian Acad Sci, MTA SE Neuropsychopharmacol & Neurochem Res Grp, Budapest, Hungary.;Semmelweis Univ, Kutvolgyi Clin Ctr, Dept Psychiat & Psychotherapy, Budapest, Hungary..
    Grabe, H. J.
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany..
    Holzman, C.
    Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA..
    Johnson, E. O.
    RTI Int, Fellow Program, Res Triangle Pk, NC USA.;RTI Int, Behav Hlth & Criminal Justice Div, Res Triangle Pk, NC USA..
    Kennedy, M.
    Univ Otago, Dept Pathol, Christchurch, New Zealand..
    Laucht, M.
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany..
    Martin, N. G.
    QIMR Berghofer, Genet Epidemiol, Brisbane, Qld, Australia..
    Munafo, M. R.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.;Univ Bristol, Sch Expt Psychol, UK Ctr Tobacco & Alcohol Studies, Bristol, Avon, England..
    Nillson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp Västerås, Västerås, Sweden..
    Oldehinkel, A. J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Olsson, C. A.
    Deakin Univ Geelong, Ctr Social & Early Emot Dev, Sch Psychol, Fac Hlth, Burwood, Vic, Australia.;Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia.;Univ Melbourne, Sch Psychol Sci, Melbourne, Vic, Australia.;Murdoch Childrens Res Inst, Ctr Adolescent Hlth, Melbourne, Vic, Australia..
    Ormel, J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Otte, C.
    Charite, Klin Psychiat & Psychotherapie Campus Benjamin Fr, Berlin, Germany..
    Patton, G. C.
    Univ Melbourne, Murdoch Childrens Res Inst, Dept Paediat, Melbourne, Vic, Australia..
    Penninx, B. W. J. H.
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;GGZ InGeest, Amsterdam, Netherlands..
    Ritchie, K.
    INSERM, Neuropsychiat U1061, Montpellier, France..
    Sarchiapone, M.
    Univ Molise, Dept Hlth Sci, Campobasso, Italy..
    Scheid, J. M.
    Michigan State Univ, Dept Psychiat, E Lansing, MI 48824 USA..
    Serretti, A.
    Univ Bologna, Dept Biomed & NeuroMotor Sci, Bologna, Italy..
    Smit, J. H.
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;GGZ InGeest, Amsterdam, Netherlands..
    Stefanis, N. C.
    Univ Athens, Sch Med, Eginit Hosp, Dept Psychiat, Athens, Greece.;Theodor Theohari Cozzika Fdn, Neurobiol Res Inst, Athens, Greece..
    Surtees, P. G.
    Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Voelzke, H.
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Weinstein, M.
    Georgetown Univ, Ctr Populat & Hlth, Washington, DC USA..
    Whooley, M.
    Vet Affairs Hlth Care Syst, San Francisco, CA USA.;Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Nurnberger, J. I., Jr.
    Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA.;Indiana Univ Sch Med, Dept Med & Mol Genet, Inst Psychiat Res, Indianapolis, IN 46202 USA..
    Breslau, N.
    Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA..
    Bierut, L. J.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 1, p. 133-142Article in journal (Refereed)
    Abstract [en]

    The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

  • 125. Culverhouse, Robert C
    et al.
    Bowes, Lucy
    Breslau, Naomi
    Nurnberger, John I
    Burmeister, Margit
    Fergusson, David M
    Munafò, Marcus
    Saccone, Nancy L
    Bierut, Laura J
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression.2013In: BMC psychiatry, ISSN 1471-244X, Vol. 13, p. 304-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions.

    METHODS/DESIGN: To improve understanding of the combined roles of 5-HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression.

    STUDY ELIGIBILITY CRITERIA: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias.

    DATA SOURCES: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants.The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results.

    DISCUSSION: Variation in 5-HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion.

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