PMC:4024607 / 6365-14167 JSONTXT

{"project":"0_colil","denotations":[{"id":"24959326-20797380-27641","span":{"begin":4437,"end":4441},"obj":"20797380"},{"id":"24959326-20797380-27642","span":{"begin":5125,"end":5129},"obj":"20797380"}],"text":"Method\n\nStudy setting\nFemale patients with a diagnosis of BPD were recruited between 1999 and 2004 for a psychotherapy treatment outcome study: “Stockholm county council and Karolinska Institute Psychotherapy project for suicide-prone women” (SKIP project). The SKIP project is a randomized controlled trial, comparing the efficacies of two forms of psychotherapy, and general psychiatric care (treatment as usual). The Regional Ethical Review Board in Stockholm approved the study protocol (Dnr. 95-283) and the participants gave their written informed consent to the study.\nInclusion criteria were a history of at least two suicide attempts (defined as a self-destructive act with some degree of intent to die), borderline diagnosis according to DSM–IV, a fair capacity to communicate verbally and in writing in the Swedish language, and aged between 18 and 50 years. Exclusion criteria were schizophrenia spectrum psychosis, melancholia, mental retardation, drug abuse and severe anorexia.\n\nPatients\nA total of 162 women with BPD were invited to take part in the SKIP project. Of these individuals, 14 declined to join the study, 41 were excluded due to not fulfilling inclusion criteria or to fulfilling exclusion criteria and one completed suicide before joining the study. Thus, out of 162 women, 106 (65%) took part in the SKIP study. We obtained laboratory data for 97 of 106 individuals; 92 patients were euthyroid (TSH reference range: 0.4–3.5 mE/l, Karolinska University Hospital) and thus included in the statistical analyses described below.\nThe mean age of the patients was 29.5 years (SD=7.6; range 19–50). The participants were interviewed by a trained psychiatrist, using the SCID I research version interview to establish the DSM–IV diagnoses (First, Spitzer, Gibbon, \u0026 Williams, 1997). Trained clinical psychologists established Axis II diagnoses by DIP–I interviews (Ottosson et al., 1995). All self-rating scales were completed under the supervision of a research nurse. 90 (98%) of the participants had at least one current Axis I psychiatric diagnosis. Among the Axis I diagnoses, 78 (85%) of the patients met the criteria for mood disorders (unipolar major depressive disorder, single episode or recurrent, bipolar disorder, depressed or dysthymic disorder), 76 (83%) for anxiety disorders. Forty nine out of 92 (53%) patients met the criteria of PTSD. 24 (26%) had a comorbid eating disorder; of whom 16 (17%) with bulimia and eight (9%) with anorexia nervosa. Eight women (9%) had a diagnosis of alcohol abuse. Fifty women had an additional personality disorder (PD); avoidant PD (n=24), paranoid PD (n=15), obsessive–compulsive PD (n=12), histrionic PD (n=10), dependent PD (n=9), narcissistic PD (n=4). 22 (24%) women had three or more personality disorders. The criteria for conduct disorder were met in seven of the women. Medication records were obtained for 68 (74%) of the patients, of whom seven patients were medication-free. Three patients were treated with lithium. The most frequent medications were venlafaxin (n=12), fluoxetine (n=11), sertraline (n=9) and citalopram (n=4). Two patients had a combination of two antidepressants.\n\nNeuroendocrine testing\nBaseline thyroid function was evaluated by measuring plasma free and bound T3, T4 and TSH levels. Venous blood was drawn and immediately frozen in aliquots at −70°C or below until analyzed. The samples were thawed and analyzed by immunoassays (Unicel DxI 800 Beckman Coulter, for FT4, FT3 and TSH and AutoDelfia, for T4 and T3) in the year 2010. No prior thawing of the frozen plasma samples had been performed. The Karolinska Laboratory at Karolinska University Hospital performed all analyses according to accredited routines. The intra-assay coefficient of variation for TSH was 3.85–5.56%, for FT4 2.74–4.4%, for FT3 5.1–6.6%, for T4 2.7–3.6% and for T3 2.9–3.1%. The inter-assay coefficient of variation for TSH was 3.02–3.68%, for FT4 3.34–8.08%, for FT3 1.3–8%, for T4 1.4–2.2% and for T3 1.2–2.1%. Analytical interferences in thyroid hormone testing are estimated to occur in less than 0.1%, at the Karolinska Clinical Laboratory. The FT3/FT4 ratio was used to estimate peripheral deiodination. Preanalytical variation was minimized by performing the venipuncture in a standardized manner for all participants, of which the majority was sampled at noon.\n\nAssessments\nThe Karolinska Interpersonal Violence Scale (KIVS) (Jokinen et al., 2010) contains four subscales with direct questions with concrete examples of exposure to violence and expressed violent behavior in childhood (aged 6–14 years) and during adult life (15 years or older). The ratings are filled in during a structured interview to elicit a comprehensive lifetime trauma and victimization history and history of lifetime expressed violent behavior. Interviews and ratings (0–5 for each subscale, total 20) were performed and assessed by trained psychiatrists. The inter-rater reliability of the KIVS subscales was high (r\u003e0.9). The KIVS scale has been validated against several other rating scales measuring aggression and acts of violence (Jokinen et al., 2010). The KIVS scores were grouped into three levels of exposure to interpersonal violence as a child: score 0 and 1 representing “no exposure or mild level of exposure,” score 2 and 3 representing “medium high level of exposure,” and score 4 and 5 representing “high level of exposure” (see Table 1).\nTable 1 The KIVS scores grouped into three levels of exposure\n\nStatistical analysis\nOne female was identified as both a univariate and a multivariate outlier. The exclusion of this individual did not affect the results and she was therefore included in all analyses. Correlation analyses were used to determine associations between the clinical ratings and biological variables. Initially, tests of nonparametric or parametric correlations were performed using Spearman's rho or Pearson's r. Some variables were analyzed by both non-parametric as well as parametric statistical methods due to the non-normality of sample distributions; however, the choice of statistical method did not change the results. Therefore, for the sake of brevity we only report parametric statistics. Group differences were computed with one-way ANOVA or with Wilcoxon test in continuous variables. For categorical variables, the group comparisons were calculated using the Chi-square test. Effect sizes for significant Chi-square tests were expressed as Kendall's tau-c and interpreted as weak association (0.10–0.20), moderate association (0.20–0.40), relatively strong association (0.40–0.60), strong association (0.60–0.80), or very strong association (0.80–1.00). If the expected number was \u003c5 in any of the cells, the Chi-square test was not performed. Based on the results of bivariate analyses, the association between FT3/FT4 ratio and exposure to interpersonal violence as a child was computed with multiple regression analysis adjusted for age, PTSD, plasma cortisol and sample storage time. The residual scatterplots were examined to check the assumptions of normality, linearity and homoscedasticity between the predicted dependent variable scores and errors of prediction, and the assumptions were deemed to be satisfied. Furthermore, the Durbin-Watson test statistic expressed no correlation in adjacent residuals and the variance inflation factor (VIF) and tolerance statistic indicated no problem with multicollinearity. In order to preserve most of the sample size and thereby statistical power, missing data was handled by pairwise deletion in the statistical analyses. The alpha level was set on \u003c0.05 while p-values 0.05\u003cp\u003c0.10 were regarded as statistical trends. The statistical analysis was performed using the SPSS statistical software package (IBM, SPSS™, version 22).\n"}

{"project":"2_test","denotations":[{"id":"24959326-20797380-29259686","span":{"begin":4437,"end":4441},"obj":"20797380"},{"id":"24959326-20797380-29259687","span":{"begin":5125,"end":5129},"obj":"20797380"}],"text":"Method\n\nStudy setting\nFemale patients with a diagnosis of BPD were recruited between 1999 and 2004 for a psychotherapy treatment outcome study: “Stockholm county council and Karolinska Institute Psychotherapy project for suicide-prone women” (SKIP project). The SKIP project is a randomized controlled trial, comparing the efficacies of two forms of psychotherapy, and general psychiatric care (treatment as usual). The Regional Ethical Review Board in Stockholm approved the study protocol (Dnr. 95-283) and the participants gave their written informed consent to the study.\nInclusion criteria were a history of at least two suicide attempts (defined as a self-destructive act with some degree of intent to die), borderline diagnosis according to DSM–IV, a fair capacity to communicate verbally and in writing in the Swedish language, and aged between 18 and 50 years. Exclusion criteria were schizophrenia spectrum psychosis, melancholia, mental retardation, drug abuse and severe anorexia.\n\nPatients\nA total of 162 women with BPD were invited to take part in the SKIP project. Of these individuals, 14 declined to join the study, 41 were excluded due to not fulfilling inclusion criteria or to fulfilling exclusion criteria and one completed suicide before joining the study. Thus, out of 162 women, 106 (65%) took part in the SKIP study. We obtained laboratory data for 97 of 106 individuals; 92 patients were euthyroid (TSH reference range: 0.4–3.5 mE/l, Karolinska University Hospital) and thus included in the statistical analyses described below.\nThe mean age of the patients was 29.5 years (SD=7.6; range 19–50). The participants were interviewed by a trained psychiatrist, using the SCID I research version interview to establish the DSM–IV diagnoses (First, Spitzer, Gibbon, \u0026 Williams, 1997). Trained clinical psychologists established Axis II diagnoses by DIP–I interviews (Ottosson et al., 1995). All self-rating scales were completed under the supervision of a research nurse. 90 (98%) of the participants had at least one current Axis I psychiatric diagnosis. Among the Axis I diagnoses, 78 (85%) of the patients met the criteria for mood disorders (unipolar major depressive disorder, single episode or recurrent, bipolar disorder, depressed or dysthymic disorder), 76 (83%) for anxiety disorders. Forty nine out of 92 (53%) patients met the criteria of PTSD. 24 (26%) had a comorbid eating disorder; of whom 16 (17%) with bulimia and eight (9%) with anorexia nervosa. Eight women (9%) had a diagnosis of alcohol abuse. Fifty women had an additional personality disorder (PD); avoidant PD (n=24), paranoid PD (n=15), obsessive–compulsive PD (n=12), histrionic PD (n=10), dependent PD (n=9), narcissistic PD (n=4). 22 (24%) women had three or more personality disorders. The criteria for conduct disorder were met in seven of the women. Medication records were obtained for 68 (74%) of the patients, of whom seven patients were medication-free. Three patients were treated with lithium. The most frequent medications were venlafaxin (n=12), fluoxetine (n=11), sertraline (n=9) and citalopram (n=4). Two patients had a combination of two antidepressants.\n\nNeuroendocrine testing\nBaseline thyroid function was evaluated by measuring plasma free and bound T3, T4 and TSH levels. Venous blood was drawn and immediately frozen in aliquots at −70°C or below until analyzed. The samples were thawed and analyzed by immunoassays (Unicel DxI 800 Beckman Coulter, for FT4, FT3 and TSH and AutoDelfia, for T4 and T3) in the year 2010. No prior thawing of the frozen plasma samples had been performed. The Karolinska Laboratory at Karolinska University Hospital performed all analyses according to accredited routines. The intra-assay coefficient of variation for TSH was 3.85–5.56%, for FT4 2.74–4.4%, for FT3 5.1–6.6%, for T4 2.7–3.6% and for T3 2.9–3.1%. The inter-assay coefficient of variation for TSH was 3.02–3.68%, for FT4 3.34–8.08%, for FT3 1.3–8%, for T4 1.4–2.2% and for T3 1.2–2.1%. Analytical interferences in thyroid hormone testing are estimated to occur in less than 0.1%, at the Karolinska Clinical Laboratory. The FT3/FT4 ratio was used to estimate peripheral deiodination. Preanalytical variation was minimized by performing the venipuncture in a standardized manner for all participants, of which the majority was sampled at noon.\n\nAssessments\nThe Karolinska Interpersonal Violence Scale (KIVS) (Jokinen et al., 2010) contains four subscales with direct questions with concrete examples of exposure to violence and expressed violent behavior in childhood (aged 6–14 years) and during adult life (15 years or older). The ratings are filled in during a structured interview to elicit a comprehensive lifetime trauma and victimization history and history of lifetime expressed violent behavior. Interviews and ratings (0–5 for each subscale, total 20) were performed and assessed by trained psychiatrists. The inter-rater reliability of the KIVS subscales was high (r\u003e0.9). The KIVS scale has been validated against several other rating scales measuring aggression and acts of violence (Jokinen et al., 2010). The KIVS scores were grouped into three levels of exposure to interpersonal violence as a child: score 0 and 1 representing “no exposure or mild level of exposure,” score 2 and 3 representing “medium high level of exposure,” and score 4 and 5 representing “high level of exposure” (see Table 1).\nTable 1 The KIVS scores grouped into three levels of exposure\n\nStatistical analysis\nOne female was identified as both a univariate and a multivariate outlier. The exclusion of this individual did not affect the results and she was therefore included in all analyses. Correlation analyses were used to determine associations between the clinical ratings and biological variables. Initially, tests of nonparametric or parametric correlations were performed using Spearman's rho or Pearson's r. Some variables were analyzed by both non-parametric as well as parametric statistical methods due to the non-normality of sample distributions; however, the choice of statistical method did not change the results. Therefore, for the sake of brevity we only report parametric statistics. Group differences were computed with one-way ANOVA or with Wilcoxon test in continuous variables. For categorical variables, the group comparisons were calculated using the Chi-square test. Effect sizes for significant Chi-square tests were expressed as Kendall's tau-c and interpreted as weak association (0.10–0.20), moderate association (0.20–0.40), relatively strong association (0.40–0.60), strong association (0.60–0.80), or very strong association (0.80–1.00). If the expected number was \u003c5 in any of the cells, the Chi-square test was not performed. Based on the results of bivariate analyses, the association between FT3/FT4 ratio and exposure to interpersonal violence as a child was computed with multiple regression analysis adjusted for age, PTSD, plasma cortisol and sample storage time. The residual scatterplots were examined to check the assumptions of normality, linearity and homoscedasticity between the predicted dependent variable scores and errors of prediction, and the assumptions were deemed to be satisfied. Furthermore, the Durbin-Watson test statistic expressed no correlation in adjacent residuals and the variance inflation factor (VIF) and tolerance statistic indicated no problem with multicollinearity. In order to preserve most of the sample size and thereby statistical power, missing data was handled by pairwise deletion in the statistical analyses. The alpha level was set on \u003c0.05 while p-values 0.05\u003cp\u003c0.10 were regarded as statistical trends. The statistical analysis was performed using the SPSS statistical software package (IBM, SPSS™, version 22).\n"}

{"project":"MyTest","denotations":[{"id":"24959326-20797380-29259686","span":{"begin":4437,"end":4441},"obj":"20797380"},{"id":"24959326-20797380-29259687","span":{"begin":5125,"end":5129},"obj":"20797380"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Method\n\nStudy setting\nFemale patients with a diagnosis of BPD were recruited between 1999 and 2004 for a psychotherapy treatment outcome study: “Stockholm county council and Karolinska Institute Psychotherapy project for suicide-prone women” (SKIP project). The SKIP project is a randomized controlled trial, comparing the efficacies of two forms of psychotherapy, and general psychiatric care (treatment as usual). The Regional Ethical Review Board in Stockholm approved the study protocol (Dnr. 95-283) and the participants gave their written informed consent to the study.\nInclusion criteria were a history of at least two suicide attempts (defined as a self-destructive act with some degree of intent to die), borderline diagnosis according to DSM–IV, a fair capacity to communicate verbally and in writing in the Swedish language, and aged between 18 and 50 years. Exclusion criteria were schizophrenia spectrum psychosis, melancholia, mental retardation, drug abuse and severe anorexia.\n\nPatients\nA total of 162 women with BPD were invited to take part in the SKIP project. Of these individuals, 14 declined to join the study, 41 were excluded due to not fulfilling inclusion criteria or to fulfilling exclusion criteria and one completed suicide before joining the study. Thus, out of 162 women, 106 (65%) took part in the SKIP study. We obtained laboratory data for 97 of 106 individuals; 92 patients were euthyroid (TSH reference range: 0.4–3.5 mE/l, Karolinska University Hospital) and thus included in the statistical analyses described below.\nThe mean age of the patients was 29.5 years (SD=7.6; range 19–50). The participants were interviewed by a trained psychiatrist, using the SCID I research version interview to establish the DSM–IV diagnoses (First, Spitzer, Gibbon, \u0026 Williams, 1997). Trained clinical psychologists established Axis II diagnoses by DIP–I interviews (Ottosson et al., 1995). All self-rating scales were completed under the supervision of a research nurse. 90 (98%) of the participants had at least one current Axis I psychiatric diagnosis. Among the Axis I diagnoses, 78 (85%) of the patients met the criteria for mood disorders (unipolar major depressive disorder, single episode or recurrent, bipolar disorder, depressed or dysthymic disorder), 76 (83%) for anxiety disorders. Forty nine out of 92 (53%) patients met the criteria of PTSD. 24 (26%) had a comorbid eating disorder; of whom 16 (17%) with bulimia and eight (9%) with anorexia nervosa. Eight women (9%) had a diagnosis of alcohol abuse. Fifty women had an additional personality disorder (PD); avoidant PD (n=24), paranoid PD (n=15), obsessive–compulsive PD (n=12), histrionic PD (n=10), dependent PD (n=9), narcissistic PD (n=4). 22 (24%) women had three or more personality disorders. The criteria for conduct disorder were met in seven of the women. Medication records were obtained for 68 (74%) of the patients, of whom seven patients were medication-free. Three patients were treated with lithium. The most frequent medications were venlafaxin (n=12), fluoxetine (n=11), sertraline (n=9) and citalopram (n=4). Two patients had a combination of two antidepressants.\n\nNeuroendocrine testing\nBaseline thyroid function was evaluated by measuring plasma free and bound T3, T4 and TSH levels. Venous blood was drawn and immediately frozen in aliquots at −70°C or below until analyzed. The samples were thawed and analyzed by immunoassays (Unicel DxI 800 Beckman Coulter, for FT4, FT3 and TSH and AutoDelfia, for T4 and T3) in the year 2010. No prior thawing of the frozen plasma samples had been performed. The Karolinska Laboratory at Karolinska University Hospital performed all analyses according to accredited routines. The intra-assay coefficient of variation for TSH was 3.85–5.56%, for FT4 2.74–4.4%, for FT3 5.1–6.6%, for T4 2.7–3.6% and for T3 2.9–3.1%. The inter-assay coefficient of variation for TSH was 3.02–3.68%, for FT4 3.34–8.08%, for FT3 1.3–8%, for T4 1.4–2.2% and for T3 1.2–2.1%. Analytical interferences in thyroid hormone testing are estimated to occur in less than 0.1%, at the Karolinska Clinical Laboratory. The FT3/FT4 ratio was used to estimate peripheral deiodination. Preanalytical variation was minimized by performing the venipuncture in a standardized manner for all participants, of which the majority was sampled at noon.\n\nAssessments\nThe Karolinska Interpersonal Violence Scale (KIVS) (Jokinen et al., 2010) contains four subscales with direct questions with concrete examples of exposure to violence and expressed violent behavior in childhood (aged 6–14 years) and during adult life (15 years or older). The ratings are filled in during a structured interview to elicit a comprehensive lifetime trauma and victimization history and history of lifetime expressed violent behavior. Interviews and ratings (0–5 for each subscale, total 20) were performed and assessed by trained psychiatrists. The inter-rater reliability of the KIVS subscales was high (r\u003e0.9). The KIVS scale has been validated against several other rating scales measuring aggression and acts of violence (Jokinen et al., 2010). The KIVS scores were grouped into three levels of exposure to interpersonal violence as a child: score 0 and 1 representing “no exposure or mild level of exposure,” score 2 and 3 representing “medium high level of exposure,” and score 4 and 5 representing “high level of exposure” (see Table 1).\nTable 1 The KIVS scores grouped into three levels of exposure\n\nStatistical analysis\nOne female was identified as both a univariate and a multivariate outlier. The exclusion of this individual did not affect the results and she was therefore included in all analyses. Correlation analyses were used to determine associations between the clinical ratings and biological variables. Initially, tests of nonparametric or parametric correlations were performed using Spearman's rho or Pearson's r. Some variables were analyzed by both non-parametric as well as parametric statistical methods due to the non-normality of sample distributions; however, the choice of statistical method did not change the results. Therefore, for the sake of brevity we only report parametric statistics. Group differences were computed with one-way ANOVA or with Wilcoxon test in continuous variables. For categorical variables, the group comparisons were calculated using the Chi-square test. Effect sizes for significant Chi-square tests were expressed as Kendall's tau-c and interpreted as weak association (0.10–0.20), moderate association (0.20–0.40), relatively strong association (0.40–0.60), strong association (0.60–0.80), or very strong association (0.80–1.00). If the expected number was \u003c5 in any of the cells, the Chi-square test was not performed. Based on the results of bivariate analyses, the association between FT3/FT4 ratio and exposure to interpersonal violence as a child was computed with multiple regression analysis adjusted for age, PTSD, plasma cortisol and sample storage time. The residual scatterplots were examined to check the assumptions of normality, linearity and homoscedasticity between the predicted dependent variable scores and errors of prediction, and the assumptions were deemed to be satisfied. Furthermore, the Durbin-Watson test statistic expressed no correlation in adjacent residuals and the variance inflation factor (VIF) and tolerance statistic indicated no problem with multicollinearity. In order to preserve most of the sample size and thereby statistical power, missing data was handled by pairwise deletion in the statistical analyses. The alpha level was set on \u003c0.05 while p-values 0.05\u003cp\u003c0.10 were regarded as statistical trends. The statistical analysis was performed using the SPSS statistical software package (IBM, SPSS™, version 22).\n"}

{"project":"NEUROSES","denotations":[{"id":"T149","span":{"begin":1425,"end":1428},"obj":"CHEBI_17842"},{"id":"T150","span":{"begin":1425,"end":1428},"obj":"CHEBI_81567"},{"id":"T151","span":{"begin":1564,"end":1567},"obj":"PATO_0000011"},{"id":"T152","span":{"begin":1564,"end":1567},"obj":"CHEBI_84123"},{"id":"T153","span":{"begin":2129,"end":2132},"obj":"CHEBI_16044"},{"id":"T154","span":{"begin":2351,"end":2354},"obj":"CHEBI_16044"},{"id":"T155","span":{"begin":2826,"end":2829},"obj":"CHEBI_16044"},{"id":"T156","span":{"begin":2129,"end":2132},"obj":"CHEBI_16811"},{"id":"T157","span":{"begin":2351,"end":2354},"obj":"CHEBI_16811"},{"id":"T158","span":{"begin":2826,"end":2829},"obj":"CHEBI_16811"},{"id":"T159","span":{"begin":2129,"end":2132},"obj":"CHEBI_16643"},{"id":"T160","span":{"begin":2351,"end":2354},"obj":"CHEBI_16643"},{"id":"T161","span":{"begin":2826,"end":2829},"obj":"CHEBI_16643"},{"id":"T162","span":{"begin":2220,"end":2229},"obj":"PATO_0000427"},{"id":"T163","span":{"begin":2522,"end":2529},"obj":"CHEBI_16236"},{"id":"T164","span":{"begin":2522,"end":2529},"obj":"CHEBI_30879"},{"id":"T165","span":{"begin":2955,"end":2959},"obj":"PATO_0002316"},{"id":"T166","span":{"begin":2994,"end":3001},"obj":"CHEBI_49713"},{"id":"T167","span":{"begin":2994,"end":3001},"obj":"CHEBI_30145"},{"id":"T168","span":{"begin":3012,"end":3020},"obj":"PATO_0000380"},{"id":"T169","span":{"begin":3057,"end":3067},"obj":"CHEBI_5118"},{"id":"T170","span":{"begin":3076,"end":3086},"obj":"CHEBI_9123"},{"id":"T171","span":{"begin":3097,"end":3107},"obj":"CHEBI_3723"},{"id":"T172","span":{"begin":3153,"end":3168},"obj":"CHEBI_35469"},{"id":"T191","span":{"begin":3487,"end":3490},"obj":"CHEBI_81567"},{"id":"T192","span":{"begin":3768,"end":3771},"obj":"CHEBI_81567"},{"id":"T193","span":{"begin":3907,"end":3910},"obj":"CHEBI_81567"},{"id":"T194","span":{"begin":3331,"end":3337},"obj":"PATO_0001985"},{"id":"T195","span":{"begin":3564,"end":3570},"obj":"PATO_0001985"},{"id":"T196","span":{"begin":3733,"end":3738},"obj":"PATO_0000003"},{"id":"T197","span":{"begin":3872,"end":3877},"obj":"PATO_0000003"},{"id":"T198","span":{"begin":4145,"end":4150},"obj":"PATO_0001038"},{"id":"T199","span":{"begin":4145,"end":4150},"obj":"PATO_0001470"},{"id":"T200","span":{"begin":4172,"end":4182},"obj":"PATO_0002107"},{"id":"T205","span":{"begin":4494,"end":4502},"obj":"PATO_0000436"},{"id":"T206","span":{"begin":4676,"end":4686},"obj":"PATO_0001411"},{"id":"T207","span":{"begin":4982,"end":4986},"obj":"PATO_0000469"},{"id":"T208","span":{"begin":5332,"end":5336},"obj":"PATO_0000469"},{"id":"T234","span":{"begin":5517,"end":5523},"obj":"PATO_0000383"},{"id":"T235","span":{"begin":5621,"end":5624},"obj":"CHEBI_52027"},{"id":"T236","span":{"begin":6107,"end":6110},"obj":"CHEBI_52027"},{"id":"T237","span":{"begin":6208,"end":6213},"obj":"CHEBI_24433"},{"id":"T238","span":{"begin":6337,"end":6342},"obj":"CHEBI_24433"},{"id":"T239","span":{"begin":6284,"end":6294},"obj":"PATO_0000689"},{"id":"T240","span":{"begin":6381,"end":6384},"obj":"CHEBI_136604"},{"id":"T241","span":{"begin":6427,"end":6430},"obj":"CHEBI_136604"},{"id":"T242","span":{"begin":6731,"end":6734},"obj":"CHEBI_136604"},{"id":"T243","span":{"begin":6385,"end":6391},"obj":"PATO_0000413"},{"id":"T244","span":{"begin":6431,"end":6437},"obj":"PATO_0000413"},{"id":"T245","span":{"begin":6735,"end":6741},"obj":"PATO_0000413"},{"id":"T246","span":{"begin":6472,"end":6475},"obj":"CHEBI_36355"},{"id":"T247","span":{"begin":6497,"end":6501},"obj":"PATO_0001779"},{"id":"T248","span":{"begin":6572,"end":6578},"obj":"PATO_0001716"},{"id":"T249","span":{"begin":6604,"end":6610},"obj":"PATO_0001716"},{"id":"T250","span":{"begin":6644,"end":6650},"obj":"PATO_0001716"},{"id":"T251","span":{"begin":6692,"end":6698},"obj":"PATO_0001056"},{"id":"T252","span":{"begin":6692,"end":6698},"obj":"PATO_0000070"},{"id":"T253","span":{"begin":6692,"end":6698},"obj":"PATO_0001555"},{"id":"T254","span":{"begin":6842,"end":6847},"obj":"PATO_0001038"},{"id":"T255","span":{"begin":6842,"end":6847},"obj":"PATO_0001470"},{"id":"T256","span":{"begin":6916,"end":6924},"obj":"PATO_0002118"},{"id":"T257","span":{"begin":6958,"end":6961},"obj":"PATO_0000011"},{"id":"T258","span":{"begin":6958,"end":6961},"obj":"CHEBI_84123"},{"id":"T259","span":{"begin":6976,"end":6984},"obj":"CHEBI_17650"},{"id":"T260","span":{"begin":7004,"end":7008},"obj":"PATO_0001309"},{"id":"T261","span":{"begin":7004,"end":7008},"obj":"PATO_0000165"},{"id":"T262","span":{"begin":7152,"end":7160},"obj":"PATO_0001227"},{"id":"T263","span":{"begin":7485,"end":7489},"obj":"PATO_0000117"},{"id":"T264","span":{"begin":7514,"end":7519},"obj":"PATO_0001024"},{"id":"T265","span":{"begin":7600,"end":7605},"obj":"CHEBI_30216"},{"id":"T266","span":{"begin":7600,"end":7605},"obj":"PATO_0001344"},{"id":"T183","span":{"begin":3203,"end":3210},"obj":"CHEBI_9584"},{"id":"T184","span":{"begin":3211,"end":3219},"obj":"PATO_0000173"},{"id":"T185","span":{"begin":3254,"end":3258},"obj":"PATO_0002316"},{"id":"T186","span":{"begin":3280,"end":3283},"obj":"CHEBI_17842"},{"id":"T187","span":{"begin":3487,"end":3490},"obj":"CHEBI_17842"},{"id":"T188","span":{"begin":3768,"end":3771},"obj":"CHEBI_17842"},{"id":"T189","span":{"begin":3907,"end":3910},"obj":"CHEBI_17842"},{"id":"T190","span":{"begin":3280,"end":3283},"obj":"CHEBI_81567"},{"id":"T139","span":{"begin":22,"end":28},"obj":"PATO_0000383"},{"id":"T140","span":{"begin":961,"end":965},"obj":"CHEBI_23888"}],"text":"Method\n\nStudy setting\nFemale patients with a diagnosis of BPD were recruited between 1999 and 2004 for a psychotherapy treatment outcome study: “Stockholm county council and Karolinska Institute Psychotherapy project for suicide-prone women” (SKIP project). The SKIP project is a randomized controlled trial, comparing the efficacies of two forms of psychotherapy, and general psychiatric care (treatment as usual). The Regional Ethical Review Board in Stockholm approved the study protocol (Dnr. 95-283) and the participants gave their written informed consent to the study.\nInclusion criteria were a history of at least two suicide attempts (defined as a self-destructive act with some degree of intent to die), borderline diagnosis according to DSM–IV, a fair capacity to communicate verbally and in writing in the Swedish language, and aged between 18 and 50 years. Exclusion criteria were schizophrenia spectrum psychosis, melancholia, mental retardation, drug abuse and severe anorexia.\n\nPatients\nA total of 162 women with BPD were invited to take part in the SKIP project. Of these individuals, 14 declined to join the study, 41 were excluded due to not fulfilling inclusion criteria or to fulfilling exclusion criteria and one completed suicide before joining the study. Thus, out of 162 women, 106 (65%) took part in the SKIP study. We obtained laboratory data for 97 of 106 individuals; 92 patients were euthyroid (TSH reference range: 0.4–3.5 mE/l, Karolinska University Hospital) and thus included in the statistical analyses described below.\nThe mean age of the patients was 29.5 years (SD=7.6; range 19–50). The participants were interviewed by a trained psychiatrist, using the SCID I research version interview to establish the DSM–IV diagnoses (First, Spitzer, Gibbon, \u0026 Williams, 1997). Trained clinical psychologists established Axis II diagnoses by DIP–I interviews (Ottosson et al., 1995). All self-rating scales were completed under the supervision of a research nurse. 90 (98%) of the participants had at least one current Axis I psychiatric diagnosis. Among the Axis I diagnoses, 78 (85%) of the patients met the criteria for mood disorders (unipolar major depressive disorder, single episode or recurrent, bipolar disorder, depressed or dysthymic disorder), 76 (83%) for anxiety disorders. Forty nine out of 92 (53%) patients met the criteria of PTSD. 24 (26%) had a comorbid eating disorder; of whom 16 (17%) with bulimia and eight (9%) with anorexia nervosa. Eight women (9%) had a diagnosis of alcohol abuse. Fifty women had an additional personality disorder (PD); avoidant PD (n=24), paranoid PD (n=15), obsessive–compulsive PD (n=12), histrionic PD (n=10), dependent PD (n=9), narcissistic PD (n=4). 22 (24%) women had three or more personality disorders. The criteria for conduct disorder were met in seven of the women. Medication records were obtained for 68 (74%) of the patients, of whom seven patients were medication-free. Three patients were treated with lithium. The most frequent medications were venlafaxin (n=12), fluoxetine (n=11), sertraline (n=9) and citalopram (n=4). Two patients had a combination of two antidepressants.\n\nNeuroendocrine testing\nBaseline thyroid function was evaluated by measuring plasma free and bound T3, T4 and TSH levels. Venous blood was drawn and immediately frozen in aliquots at −70°C or below until analyzed. The samples were thawed and analyzed by immunoassays (Unicel DxI 800 Beckman Coulter, for FT4, FT3 and TSH and AutoDelfia, for T4 and T3) in the year 2010. No prior thawing of the frozen plasma samples had been performed. The Karolinska Laboratory at Karolinska University Hospital performed all analyses according to accredited routines. The intra-assay coefficient of variation for TSH was 3.85–5.56%, for FT4 2.74–4.4%, for FT3 5.1–6.6%, for T4 2.7–3.6% and for T3 2.9–3.1%. The inter-assay coefficient of variation for TSH was 3.02–3.68%, for FT4 3.34–8.08%, for FT3 1.3–8%, for T4 1.4–2.2% and for T3 1.2–2.1%. Analytical interferences in thyroid hormone testing are estimated to occur in less than 0.1%, at the Karolinska Clinical Laboratory. The FT3/FT4 ratio was used to estimate peripheral deiodination. Preanalytical variation was minimized by performing the venipuncture in a standardized manner for all participants, of which the majority was sampled at noon.\n\nAssessments\nThe Karolinska Interpersonal Violence Scale (KIVS) (Jokinen et al., 2010) contains four subscales with direct questions with concrete examples of exposure to violence and expressed violent behavior in childhood (aged 6–14 years) and during adult life (15 years or older). The ratings are filled in during a structured interview to elicit a comprehensive lifetime trauma and victimization history and history of lifetime expressed violent behavior. Interviews and ratings (0–5 for each subscale, total 20) were performed and assessed by trained psychiatrists. The inter-rater reliability of the KIVS subscales was high (r\u003e0.9). The KIVS scale has been validated against several other rating scales measuring aggression and acts of violence (Jokinen et al., 2010). The KIVS scores were grouped into three levels of exposure to interpersonal violence as a child: score 0 and 1 representing “no exposure or mild level of exposure,” score 2 and 3 representing “medium high level of exposure,” and score 4 and 5 representing “high level of exposure” (see Table 1).\nTable 1 The KIVS scores grouped into three levels of exposure\n\nStatistical analysis\nOne female was identified as both a univariate and a multivariate outlier. The exclusion of this individual did not affect the results and she was therefore included in all analyses. Correlation analyses were used to determine associations between the clinical ratings and biological variables. Initially, tests of nonparametric or parametric correlations were performed using Spearman's rho or Pearson's r. Some variables were analyzed by both non-parametric as well as parametric statistical methods due to the non-normality of sample distributions; however, the choice of statistical method did not change the results. Therefore, for the sake of brevity we only report parametric statistics. Group differences were computed with one-way ANOVA or with Wilcoxon test in continuous variables. For categorical variables, the group comparisons were calculated using the Chi-square test. Effect sizes for significant Chi-square tests were expressed as Kendall's tau-c and interpreted as weak association (0.10–0.20), moderate association (0.20–0.40), relatively strong association (0.40–0.60), strong association (0.60–0.80), or very strong association (0.80–1.00). If the expected number was \u003c5 in any of the cells, the Chi-square test was not performed. Based on the results of bivariate analyses, the association between FT3/FT4 ratio and exposure to interpersonal violence as a child was computed with multiple regression analysis adjusted for age, PTSD, plasma cortisol and sample storage time. The residual scatterplots were examined to check the assumptions of normality, linearity and homoscedasticity between the predicted dependent variable scores and errors of prediction, and the assumptions were deemed to be satisfied. Furthermore, the Durbin-Watson test statistic expressed no correlation in adjacent residuals and the variance inflation factor (VIF) and tolerance statistic indicated no problem with multicollinearity. In order to preserve most of the sample size and thereby statistical power, missing data was handled by pairwise deletion in the statistical analyses. The alpha level was set on \u003c0.05 while p-values 0.05\u003cp\u003c0.10 were regarded as statistical trends. The statistical analysis was performed using the SPSS statistical software package (IBM, SPSS™, version 22).\n"}