PMC:4024607 / 18907-26608 JSONTXT

{"project":"0_colil","denotations":[{"id":"24959326-7956187-27643","span":{"begin":502,"end":506},"obj":"7956187"},{"id":"24959326-12193835-27644","span":{"begin":520,"end":524},"obj":"12193835"},{"id":"24959326-15184704-27645","span":{"begin":1890,"end":1894},"obj":"15184704"},{"id":"24959326-15866559-27646","span":{"begin":2154,"end":2158},"obj":"15866559"},{"id":"24959326-16782196-27647","span":{"begin":2433,"end":2437},"obj":"16782196"},{"id":"24959326-8042912-27648","span":{"begin":2722,"end":2726},"obj":"8042912"},{"id":"24959326-10204962-27649","span":{"begin":2742,"end":2746},"obj":"10204962"},{"id":"24959326-22759379-27650","span":{"begin":4780,"end":4784},"obj":"22759379"},{"id":"24959326-17978317-27651","span":{"begin":5333,"end":5337},"obj":"17978317"},{"id":"24959326-19499417-27652","span":{"begin":5626,"end":5630},"obj":"19499417"}],"text":"Discussion\nIn the present study, we measured thyroid hormones and cortisol levels in female patients with BPD and a history of suicide attempts. We measured the exposure to interpersonal violence with the Karolinska Interpersonal Violence Scale. Two thirds of the patients reported medium high or high levels of exposure to interpersonal violence as a child, which is in line with studies reporting frequent trauma exposures (up to 70%) in individuals diagnosed with BPD (Paris, Zweig-Frank, \u0026 Guzder, 1994; Yen et al., 2002). More than half of the patients fulfilled the DSM criteria for comorbid PTSD. As expected, PTSD was significantly more frequent in the high exposure group as compared to the low and the medium high groups.\nThe main finding of this study was a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4 ratio. Women with BPD exposed to interpersonal violence as a child had lower FT3/FT4 ratio. There may be a threshold of trauma exposure since the FT3/FT4 ratio was significantly lower in the high exposure group, with a KIVS scale score 4 or 5, indicating that only severe exposure to interpersonal violence as a child may be associated with an altered balance of peripheral deiodination. Interestingly, the comorbid PTSD diagnosis may have modified this relationship, the finding being significant only in patients with PTSD. Furthermore, in patients with PTSD, the exposure to interpersonal violence showed a significant negative correlation with the FT3 levels. To the best of our knowledge this is the first study measuring thyroid hormones in relation to reported exposure to interpersonal violence as a child in a large group of women with BPD.\nEarlier studies with different clinical populations have reported a positive association between FT3/FT4 ratios and a history of childhood trauma. In a study by Girdler et al. (2004), women with premenstrual dysphoric disorder (PMDD) and a history of sexual abuse showed a greater FT3/FT4 ratio, as compared to women with PMDD and no history of sexual abuse as well as healthy controls. Friedman, Wang, Jalowiec, McHugo, and McDonagh-Coyle (2005) found significant elevations in TT3/FT4 and a significant reduction in TSH, in a community sample of 63 women with PTSD due to childhood sexual abuse as compared to 42 women without PTSD, of whom 17% also reported childhood sexual abuse.\nAs summarized in a report by Wang (2006), elevated T3 levels have earlier been reported in Vietnam, Israeli, World War II and Croatian combat veteran samples with PTSD. Studies of Vietnam veterans have reported elevated FT3/FT4 and TT3/FT4 ratios, in participants with PTSD, as compared to the non-PTSD group (Mason et al., 1994; Wang \u0026 Mason, 1999). In our study, levels of FT3 and FT3/FT4 ratio were higher, though not statistically significant in the comorbid PTSD group, as compared to the non-PTSD group.\nThere may be several reasons for the differences between the studies. First and foremost, the study populations differed with respect to gender, age and diagnosis. Secondly, the type, timing and duration of trauma exposure differed between the studies. The experience of stress elicits certain neurobiological mechanisms of in the HPT axis, with an increase of free thyroid hormones in the serum in conjunction with an increase of excretion via urine, leaving serum thyroid levels unchanged (Habermann et al., 1978) or within reference interval. KIVS measures different types of interpersonal violence including sexual violence. The nature of the trauma (physical or neglect), traumatic duration, setting of trauma, timing (i.e., stress exposure during certain developmental stages of the brain), and multiplicity of childhood traumata may evoke different mechanisms of stress regulation. Since the KIVS focus on interpersonal violence, neglect was not assessed in this present study. Longitudinal studies with stratification of traumatic exposure are sparse.\nSevere and prolonged traumatic stress may expose the body and brain to physiological burdens in the stress-response systems at the level of both neurotransmitters as well as neuroendocrine interactions, leaving either permanent changes or shifting the body metabolism from homeostasis, into allostasis; a new adaptive physiological or behavioral state, maybe through epigenetic mechanisms. The impact of severe trauma may be likened to an allostatic overload, forcing the individual to adapt to new hormonal set points, in order to survive the demanding environment. This may be reflected in altered hormonal levels within normal reference ranges. Moreover, processes not contingent of thyroid hormone levels may have effect on regulation on thyroid hormone levels among individuals (Costa-e-Sousa \u0026 Hollenberg, 2012). These processes may include genetically determined tissue specific local deiodination and cell membrane thyroid hormone transport, genetic variation in Type 1 iodothyronine deiodinase (Dayan \u0026 Panicker, 2009), as well as neuronal circuitries of energy regulatory pathways in the HPT axis of higher order than the negative feedback system.\nInterestingly, in the current study the cortisol levels were higher in women with PTSD. This may be in line with earlier studies indicating a dysregulation of HPA-axis in persons with PTSD (Meewisse et al., 2007). However, the high cortisol levels may also be the result of severity of BPD, comorbid depression, or the interaction between PTSD and BPD. In addition, individuals with BPD have been suggested to express hypercortisolemia in analogy with major depressive states (Zimmerman \u0026 Choi-Kain, 2009). We observed a weak but statistically significant relationship between sample storage time and FT3; therefore, we adjusted for sample storage time in the final regression model. However, the timing of blood sampling did not have a significant effect on hormone levels.\nAmong the limitations of this study is the cross-sectional study design, which prevents us from drawing casual conclusions. As the great majority of the patients were suffering from depression and had a history of severe suicidal behavior, we could not assess if the hormone levels were associated specifically to the depressive state or to the suicidal behavior. However, there were no significant differences in frequencies of antidepressants in different exposure groups. It is also worth mentioning that the study sample may not be representative of all BPD patients due to the specific selection criteria (i.e., history of at least two suicide attempts). Since the study was originally designed as a psychotherapy treatment study, it may be regarded as a convenience sample. Unfortunately, we did not have data of whether the women were in either luteal of follicular phase, which can be regarded as a limitation. Furthermore, three patients were taking lithium that is known to affect the thyroid hormone levels.\nThe strength of this study is the relatively large sample of women with thoroughly assessed DSM diagnosis of BPD. Furthermore, the study population is relatively homogenous with regard to age, gender, diagnosis and history of suicidal behavior, which should have lowered the variance due to unique adaptive metabolic mechanisms between individuals.\nIn summary, we found a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4, among 92 women with BPD. Comorbid diagnosis of PTSD was related to a more pronounced neuroendocrine dysregulation. It would be of great value to observe thyroid hormone changes in future longitudinal studies comprising individuals with and without PTSD, in order to capture time-related neuroendocrine variability."}

{"project":"2_test","denotations":[{"id":"24959326-7956187-29259688","span":{"begin":502,"end":506},"obj":"7956187"},{"id":"24959326-12193835-29259689","span":{"begin":520,"end":524},"obj":"12193835"},{"id":"24959326-15184704-29259690","span":{"begin":1890,"end":1894},"obj":"15184704"},{"id":"24959326-15866559-29259691","span":{"begin":2154,"end":2158},"obj":"15866559"},{"id":"24959326-16782196-29259692","span":{"begin":2433,"end":2437},"obj":"16782196"},{"id":"24959326-8042912-29259693","span":{"begin":2722,"end":2726},"obj":"8042912"},{"id":"24959326-10204962-29259694","span":{"begin":2742,"end":2746},"obj":"10204962"},{"id":"24959326-22759379-29259695","span":{"begin":4780,"end":4784},"obj":"22759379"},{"id":"24959326-17978317-29259696","span":{"begin":5333,"end":5337},"obj":"17978317"},{"id":"24959326-19499417-29259697","span":{"begin":5626,"end":5630},"obj":"19499417"}],"text":"Discussion\nIn the present study, we measured thyroid hormones and cortisol levels in female patients with BPD and a history of suicide attempts. We measured the exposure to interpersonal violence with the Karolinska Interpersonal Violence Scale. Two thirds of the patients reported medium high or high levels of exposure to interpersonal violence as a child, which is in line with studies reporting frequent trauma exposures (up to 70%) in individuals diagnosed with BPD (Paris, Zweig-Frank, \u0026 Guzder, 1994; Yen et al., 2002). More than half of the patients fulfilled the DSM criteria for comorbid PTSD. As expected, PTSD was significantly more frequent in the high exposure group as compared to the low and the medium high groups.\nThe main finding of this study was a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4 ratio. Women with BPD exposed to interpersonal violence as a child had lower FT3/FT4 ratio. There may be a threshold of trauma exposure since the FT3/FT4 ratio was significantly lower in the high exposure group, with a KIVS scale score 4 or 5, indicating that only severe exposure to interpersonal violence as a child may be associated with an altered balance of peripheral deiodination. Interestingly, the comorbid PTSD diagnosis may have modified this relationship, the finding being significant only in patients with PTSD. Furthermore, in patients with PTSD, the exposure to interpersonal violence showed a significant negative correlation with the FT3 levels. To the best of our knowledge this is the first study measuring thyroid hormones in relation to reported exposure to interpersonal violence as a child in a large group of women with BPD.\nEarlier studies with different clinical populations have reported a positive association between FT3/FT4 ratios and a history of childhood trauma. In a study by Girdler et al. (2004), women with premenstrual dysphoric disorder (PMDD) and a history of sexual abuse showed a greater FT3/FT4 ratio, as compared to women with PMDD and no history of sexual abuse as well as healthy controls. Friedman, Wang, Jalowiec, McHugo, and McDonagh-Coyle (2005) found significant elevations in TT3/FT4 and a significant reduction in TSH, in a community sample of 63 women with PTSD due to childhood sexual abuse as compared to 42 women without PTSD, of whom 17% also reported childhood sexual abuse.\nAs summarized in a report by Wang (2006), elevated T3 levels have earlier been reported in Vietnam, Israeli, World War II and Croatian combat veteran samples with PTSD. Studies of Vietnam veterans have reported elevated FT3/FT4 and TT3/FT4 ratios, in participants with PTSD, as compared to the non-PTSD group (Mason et al., 1994; Wang \u0026 Mason, 1999). In our study, levels of FT3 and FT3/FT4 ratio were higher, though not statistically significant in the comorbid PTSD group, as compared to the non-PTSD group.\nThere may be several reasons for the differences between the studies. First and foremost, the study populations differed with respect to gender, age and diagnosis. Secondly, the type, timing and duration of trauma exposure differed between the studies. The experience of stress elicits certain neurobiological mechanisms of in the HPT axis, with an increase of free thyroid hormones in the serum in conjunction with an increase of excretion via urine, leaving serum thyroid levels unchanged (Habermann et al., 1978) or within reference interval. KIVS measures different types of interpersonal violence including sexual violence. The nature of the trauma (physical or neglect), traumatic duration, setting of trauma, timing (i.e., stress exposure during certain developmental stages of the brain), and multiplicity of childhood traumata may evoke different mechanisms of stress regulation. Since the KIVS focus on interpersonal violence, neglect was not assessed in this present study. Longitudinal studies with stratification of traumatic exposure are sparse.\nSevere and prolonged traumatic stress may expose the body and brain to physiological burdens in the stress-response systems at the level of both neurotransmitters as well as neuroendocrine interactions, leaving either permanent changes or shifting the body metabolism from homeostasis, into allostasis; a new adaptive physiological or behavioral state, maybe through epigenetic mechanisms. The impact of severe trauma may be likened to an allostatic overload, forcing the individual to adapt to new hormonal set points, in order to survive the demanding environment. This may be reflected in altered hormonal levels within normal reference ranges. Moreover, processes not contingent of thyroid hormone levels may have effect on regulation on thyroid hormone levels among individuals (Costa-e-Sousa \u0026 Hollenberg, 2012). These processes may include genetically determined tissue specific local deiodination and cell membrane thyroid hormone transport, genetic variation in Type 1 iodothyronine deiodinase (Dayan \u0026 Panicker, 2009), as well as neuronal circuitries of energy regulatory pathways in the HPT axis of higher order than the negative feedback system.\nInterestingly, in the current study the cortisol levels were higher in women with PTSD. This may be in line with earlier studies indicating a dysregulation of HPA-axis in persons with PTSD (Meewisse et al., 2007). However, the high cortisol levels may also be the result of severity of BPD, comorbid depression, or the interaction between PTSD and BPD. In addition, individuals with BPD have been suggested to express hypercortisolemia in analogy with major depressive states (Zimmerman \u0026 Choi-Kain, 2009). We observed a weak but statistically significant relationship between sample storage time and FT3; therefore, we adjusted for sample storage time in the final regression model. However, the timing of blood sampling did not have a significant effect on hormone levels.\nAmong the limitations of this study is the cross-sectional study design, which prevents us from drawing casual conclusions. As the great majority of the patients were suffering from depression and had a history of severe suicidal behavior, we could not assess if the hormone levels were associated specifically to the depressive state or to the suicidal behavior. However, there were no significant differences in frequencies of antidepressants in different exposure groups. It is also worth mentioning that the study sample may not be representative of all BPD patients due to the specific selection criteria (i.e., history of at least two suicide attempts). Since the study was originally designed as a psychotherapy treatment study, it may be regarded as a convenience sample. Unfortunately, we did not have data of whether the women were in either luteal of follicular phase, which can be regarded as a limitation. Furthermore, three patients were taking lithium that is known to affect the thyroid hormone levels.\nThe strength of this study is the relatively large sample of women with thoroughly assessed DSM diagnosis of BPD. Furthermore, the study population is relatively homogenous with regard to age, gender, diagnosis and history of suicidal behavior, which should have lowered the variance due to unique adaptive metabolic mechanisms between individuals.\nIn summary, we found a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4, among 92 women with BPD. Comorbid diagnosis of PTSD was related to a more pronounced neuroendocrine dysregulation. It would be of great value to observe thyroid hormone changes in future longitudinal studies comprising individuals with and without PTSD, in order to capture time-related neuroendocrine variability."}

{"project":"MyTest","denotations":[{"id":"24959326-7956187-29259688","span":{"begin":502,"end":506},"obj":"7956187"},{"id":"24959326-12193835-29259689","span":{"begin":520,"end":524},"obj":"12193835"},{"id":"24959326-15184704-29259690","span":{"begin":1890,"end":1894},"obj":"15184704"},{"id":"24959326-15866559-29259691","span":{"begin":2154,"end":2158},"obj":"15866559"},{"id":"24959326-16782196-29259692","span":{"begin":2433,"end":2437},"obj":"16782196"},{"id":"24959326-8042912-29259693","span":{"begin":2722,"end":2726},"obj":"8042912"},{"id":"24959326-10204962-29259694","span":{"begin":2742,"end":2746},"obj":"10204962"},{"id":"24959326-22759379-29259695","span":{"begin":4780,"end":4784},"obj":"22759379"},{"id":"24959326-17978317-29259696","span":{"begin":5333,"end":5337},"obj":"17978317"},{"id":"24959326-19499417-29259697","span":{"begin":5626,"end":5630},"obj":"19499417"}],"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":"Discussion\nIn the present study, we measured thyroid hormones and cortisol levels in female patients with BPD and a history of suicide attempts. We measured the exposure to interpersonal violence with the Karolinska Interpersonal Violence Scale. Two thirds of the patients reported medium high or high levels of exposure to interpersonal violence as a child, which is in line with studies reporting frequent trauma exposures (up to 70%) in individuals diagnosed with BPD (Paris, Zweig-Frank, \u0026 Guzder, 1994; Yen et al., 2002). More than half of the patients fulfilled the DSM criteria for comorbid PTSD. As expected, PTSD was significantly more frequent in the high exposure group as compared to the low and the medium high groups.\nThe main finding of this study was a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4 ratio. Women with BPD exposed to interpersonal violence as a child had lower FT3/FT4 ratio. There may be a threshold of trauma exposure since the FT3/FT4 ratio was significantly lower in the high exposure group, with a KIVS scale score 4 or 5, indicating that only severe exposure to interpersonal violence as a child may be associated with an altered balance of peripheral deiodination. Interestingly, the comorbid PTSD diagnosis may have modified this relationship, the finding being significant only in patients with PTSD. Furthermore, in patients with PTSD, the exposure to interpersonal violence showed a significant negative correlation with the FT3 levels. To the best of our knowledge this is the first study measuring thyroid hormones in relation to reported exposure to interpersonal violence as a child in a large group of women with BPD.\nEarlier studies with different clinical populations have reported a positive association between FT3/FT4 ratios and a history of childhood trauma. In a study by Girdler et al. (2004), women with premenstrual dysphoric disorder (PMDD) and a history of sexual abuse showed a greater FT3/FT4 ratio, as compared to women with PMDD and no history of sexual abuse as well as healthy controls. Friedman, Wang, Jalowiec, McHugo, and McDonagh-Coyle (2005) found significant elevations in TT3/FT4 and a significant reduction in TSH, in a community sample of 63 women with PTSD due to childhood sexual abuse as compared to 42 women without PTSD, of whom 17% also reported childhood sexual abuse.\nAs summarized in a report by Wang (2006), elevated T3 levels have earlier been reported in Vietnam, Israeli, World War II and Croatian combat veteran samples with PTSD. Studies of Vietnam veterans have reported elevated FT3/FT4 and TT3/FT4 ratios, in participants with PTSD, as compared to the non-PTSD group (Mason et al., 1994; Wang \u0026 Mason, 1999). In our study, levels of FT3 and FT3/FT4 ratio were higher, though not statistically significant in the comorbid PTSD group, as compared to the non-PTSD group.\nThere may be several reasons for the differences between the studies. First and foremost, the study populations differed with respect to gender, age and diagnosis. Secondly, the type, timing and duration of trauma exposure differed between the studies. The experience of stress elicits certain neurobiological mechanisms of in the HPT axis, with an increase of free thyroid hormones in the serum in conjunction with an increase of excretion via urine, leaving serum thyroid levels unchanged (Habermann et al., 1978) or within reference interval. KIVS measures different types of interpersonal violence including sexual violence. The nature of the trauma (physical or neglect), traumatic duration, setting of trauma, timing (i.e., stress exposure during certain developmental stages of the brain), and multiplicity of childhood traumata may evoke different mechanisms of stress regulation. Since the KIVS focus on interpersonal violence, neglect was not assessed in this present study. Longitudinal studies with stratification of traumatic exposure are sparse.\nSevere and prolonged traumatic stress may expose the body and brain to physiological burdens in the stress-response systems at the level of both neurotransmitters as well as neuroendocrine interactions, leaving either permanent changes or shifting the body metabolism from homeostasis, into allostasis; a new adaptive physiological or behavioral state, maybe through epigenetic mechanisms. The impact of severe trauma may be likened to an allostatic overload, forcing the individual to adapt to new hormonal set points, in order to survive the demanding environment. This may be reflected in altered hormonal levels within normal reference ranges. Moreover, processes not contingent of thyroid hormone levels may have effect on regulation on thyroid hormone levels among individuals (Costa-e-Sousa \u0026 Hollenberg, 2012). These processes may include genetically determined tissue specific local deiodination and cell membrane thyroid hormone transport, genetic variation in Type 1 iodothyronine deiodinase (Dayan \u0026 Panicker, 2009), as well as neuronal circuitries of energy regulatory pathways in the HPT axis of higher order than the negative feedback system.\nInterestingly, in the current study the cortisol levels were higher in women with PTSD. This may be in line with earlier studies indicating a dysregulation of HPA-axis in persons with PTSD (Meewisse et al., 2007). However, the high cortisol levels may also be the result of severity of BPD, comorbid depression, or the interaction between PTSD and BPD. In addition, individuals with BPD have been suggested to express hypercortisolemia in analogy with major depressive states (Zimmerman \u0026 Choi-Kain, 2009). We observed a weak but statistically significant relationship between sample storage time and FT3; therefore, we adjusted for sample storage time in the final regression model. However, the timing of blood sampling did not have a significant effect on hormone levels.\nAmong the limitations of this study is the cross-sectional study design, which prevents us from drawing casual conclusions. As the great majority of the patients were suffering from depression and had a history of severe suicidal behavior, we could not assess if the hormone levels were associated specifically to the depressive state or to the suicidal behavior. However, there were no significant differences in frequencies of antidepressants in different exposure groups. It is also worth mentioning that the study sample may not be representative of all BPD patients due to the specific selection criteria (i.e., history of at least two suicide attempts). Since the study was originally designed as a psychotherapy treatment study, it may be regarded as a convenience sample. Unfortunately, we did not have data of whether the women were in either luteal of follicular phase, which can be regarded as a limitation. Furthermore, three patients were taking lithium that is known to affect the thyroid hormone levels.\nThe strength of this study is the relatively large sample of women with thoroughly assessed DSM diagnosis of BPD. Furthermore, the study population is relatively homogenous with regard to age, gender, diagnosis and history of suicidal behavior, which should have lowered the variance due to unique adaptive metabolic mechanisms between individuals.\nIn summary, we found a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4, among 92 women with BPD. Comorbid diagnosis of PTSD was related to a more pronounced neuroendocrine dysregulation. It would be of great value to observe thyroid hormone changes in future longitudinal studies comprising individuals with and without PTSD, in order to capture time-related neuroendocrine variability."}

{"project":"NEUROSES","denotations":[{"id":"T400","span":{"begin":18,"end":25},"obj":"PATO_0000467"},{"id":"T401","span":{"begin":66,"end":74},"obj":"CHEBI_17650"},{"id":"T402","span":{"begin":85,"end":91},"obj":"PATO_0000383"},{"id":"T403","span":{"begin":289,"end":293},"obj":"PATO_0000469"},{"id":"T404","span":{"begin":297,"end":301},"obj":"PATO_0000469"},{"id":"T405","span":{"begin":661,"end":665},"obj":"PATO_0000469"},{"id":"T406","span":{"begin":719,"end":723},"obj":"PATO_0000469"},{"id":"T407","span":{"begin":1054,"end":1058},"obj":"PATO_0000469"},{"id":"T408","span":{"begin":399,"end":407},"obj":"PATO_0000380"},{"id":"T409","span":{"begin":645,"end":653},"obj":"PATO_0000380"},{"id":"T410","span":{"begin":572,"end":575},"obj":"CHEBI_38624"},{"id":"T411","span":{"begin":675,"end":680},"obj":"CHEBI_24433"},{"id":"T412","span":{"begin":1068,"end":1073},"obj":"CHEBI_24433"},{"id":"T413","span":{"begin":700,"end":703},"obj":"PATO_0000471"},{"id":"T414","span":{"begin":863,"end":868},"obj":"PATO_0001470"},{"id":"T415","span":{"begin":948,"end":953},"obj":"PATO_0001470"},{"id":"T416","span":{"begin":1017,"end":1022},"obj":"PATO_0001470"},{"id":"T417","span":{"begin":863,"end":868},"obj":"PATO_0001038"},{"id":"T418","span":{"begin":948,"end":953},"obj":"PATO_0001038"},{"id":"T419","span":{"begin":1017,"end":1022},"obj":"PATO_0001038"},{"id":"T420","span":{"begin":885,"end":892},"obj":"PATO_0001646"},{"id":"T421","span":{"begin":885,"end":892},"obj":"PATO_0002425"},{"id":"T422","span":{"begin":970,"end":979},"obj":"PATO_0000152"},{"id":"T423","span":{"begin":1215,"end":1222},"obj":"CHEBI_3612"},{"id":"T424","span":{"begin":1215,"end":1222},"obj":"PATO_0000185"},{"id":"T425","span":{"begin":1226,"end":1236},"obj":"PATO_0002107"},{"id":"T426","span":{"begin":1682,"end":1687},"obj":"PATO_0000586"},{"id":"T427","span":{"begin":1688,"end":1693},"obj":"CHEBI_24433"},{"id":"T428","span":{"begin":2701,"end":2706},"obj":"CHEBI_24433"},{"id":"T429","span":{"begin":2901,"end":2906},"obj":"CHEBI_24433"},{"id":"T430","span":{"begin":2002,"end":2007},"obj":"PATO_0001038"},{"id":"T431","span":{"begin":2002,"end":2007},"obj":"PATO_0001470"},{"id":"T432","span":{"begin":2231,"end":2234},"obj":"CHEBI_17842"},{"id":"T433","span":{"begin":2231,"end":2234},"obj":"CHEBI_81567"},{"id":"T434","span":{"begin":2440,"end":2448},"obj":"PATO_0001688"},{"id":"T435","span":{"begin":2609,"end":2617},"obj":"PATO_0001688"},{"id":"T436","span":{"begin":3053,"end":3056},"obj":"PATO_0000011"},{"id":"T437","span":{"begin":3053,"end":3056},"obj":"CHEBI_84123"},{"id":"T438","span":{"begin":3103,"end":3111},"obj":"PATO_0001309"},{"id":"T439","span":{"begin":3595,"end":3603},"obj":"PATO_0001309"},{"id":"T440","span":{"begin":3269,"end":3273},"obj":"PATO_0002316"},{"id":"T441","span":{"begin":3374,"end":3381},"obj":"CHEBI_9584"},{"id":"T442","span":{"begin":3785,"end":3795},"obj":"PATO_0000076"},{"id":"T443","span":{"begin":3812,"end":3817},"obj":"PATO_0001516"},{"id":"T444","span":{"begin":3878,"end":3885},"obj":"PATO_0000467"},{"id":"T445","span":{"begin":3919,"end":3933},"obj":"PATO_0002067"},{"id":"T446","span":{"begin":3960,"end":3966},"obj":"PATO_0001609"},{"id":"T447","span":{"begin":4113,"end":4130},"obj":"CHEBI_25512"},{"id":"T448","span":{"begin":4186,"end":4195},"obj":"PATO_0002293"},{"id":"T449","span":{"begin":4591,"end":4597},"obj":"PATO_0000461"},{"id":"T450","span":{"begin":4696,"end":4706},"obj":"PATO_0000076"},{"id":"T451","span":{"begin":4946,"end":4959},"obj":"CHEBI_24864"},{"id":"T452","span":{"begin":5032,"end":5038},"obj":"PATO_0001021"},{"id":"T453","span":{"begin":5166,"end":5174},"obj":"CHEBI_17650"},{"id":"T454","span":{"begin":5358,"end":5366},"obj":"CHEBI_17650"},{"id":"T455","span":{"begin":5285,"end":5288},"obj":"CHEBI_29031"},{"id":"T456","span":{"begin":5285,"end":5288},"obj":"CHEBI_61431"},{"id":"T457","span":{"begin":5285,"end":5288},"obj":"CHEBI_53393"},{"id":"T458","span":{"begin":5285,"end":5288},"obj":"CHEBI_64342"},{"id":"T459","span":{"begin":5353,"end":5357},"obj":"PATO_0000469"},{"id":"T460","span":{"begin":5718,"end":5722},"obj":"PATO_0000165"},{"id":"T461","span":{"begin":5774,"end":5778},"obj":"PATO_0000165"},{"id":"T462","span":{"begin":5718,"end":5722},"obj":"PATO_0001309"},{"id":"T463","span":{"begin":5774,"end":5778},"obj":"PATO_0001309"},{"id":"T464","span":{"begin":5848,"end":5851},"obj":"CHEBI_52027"},{"id":"T465","span":{"begin":5885,"end":5892},"obj":"CHEBI_24621"},{"id":"T466","span":{"begin":5944,"end":5959},"obj":"PATO_0002006"},{"id":"T467","span":{"begin":6032,"end":6037},"obj":"PATO_0000586"},{"id":"T468","span":{"begin":6965,"end":6970},"obj":"PATO_0000586"},{"id":"T469","span":{"begin":6168,"end":6175},"obj":"CHEBI_24621"},{"id":"T470","span":{"begin":6188,"end":6198},"obj":"PATO_0001668"},{"id":"T471","span":{"begin":6330,"end":6345},"obj":"CHEBI_35469"},{"id":"T472","span":{"begin":6774,"end":6779},"obj":"PATO_0000083"},{"id":"T473","span":{"begin":6860,"end":6867},"obj":"CHEBI_49713"},{"id":"T474","span":{"begin":6860,"end":6867},"obj":"CHEBI_30145"},{"id":"T475","span":{"begin":7012,"end":7015},"obj":"CHEBI_38624"},{"id":"T476","span":{"begin":7108,"end":7111},"obj":"PATO_0000011"},{"id":"T477","span":{"begin":7108,"end":7111},"obj":"CHEBI_84123"},{"id":"T478","span":{"begin":7211,"end":7217},"obj":"PATO_0000430"},{"id":"T479","span":{"begin":7517,"end":7522},"obj":"PATO_0000586"},{"id":"T480","span":{"begin":7523,"end":7528},"obj":"PATO_0000002"},{"id":"T481","span":{"begin":7661,"end":7665},"obj":"PATO_0001309"},{"id":"T482","span":{"begin":7661,"end":7665},"obj":"PATO_0000165"},{"id":"T483","span":{"begin":7689,"end":7700},"obj":"PATO_0001303"},{"id":"T484","span":{"begin":5426,"end":5436},"obj":"PM3425"},{"id":"T485","span":{"begin":6083,"end":6093},"obj":"PM3425"},{"id":"T486","span":{"begin":5426,"end":5436},"obj":"PM3425"},{"id":"T487","span":{"begin":6083,"end":6093},"obj":"PM3425"}],"text":"Discussion\nIn the present study, we measured thyroid hormones and cortisol levels in female patients with BPD and a history of suicide attempts. We measured the exposure to interpersonal violence with the Karolinska Interpersonal Violence Scale. Two thirds of the patients reported medium high or high levels of exposure to interpersonal violence as a child, which is in line with studies reporting frequent trauma exposures (up to 70%) in individuals diagnosed with BPD (Paris, Zweig-Frank, \u0026 Guzder, 1994; Yen et al., 2002). More than half of the patients fulfilled the DSM criteria for comorbid PTSD. As expected, PTSD was significantly more frequent in the high exposure group as compared to the low and the medium high groups.\nThe main finding of this study was a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4 ratio. Women with BPD exposed to interpersonal violence as a child had lower FT3/FT4 ratio. There may be a threshold of trauma exposure since the FT3/FT4 ratio was significantly lower in the high exposure group, with a KIVS scale score 4 or 5, indicating that only severe exposure to interpersonal violence as a child may be associated with an altered balance of peripheral deiodination. Interestingly, the comorbid PTSD diagnosis may have modified this relationship, the finding being significant only in patients with PTSD. Furthermore, in patients with PTSD, the exposure to interpersonal violence showed a significant negative correlation with the FT3 levels. To the best of our knowledge this is the first study measuring thyroid hormones in relation to reported exposure to interpersonal violence as a child in a large group of women with BPD.\nEarlier studies with different clinical populations have reported a positive association between FT3/FT4 ratios and a history of childhood trauma. In a study by Girdler et al. (2004), women with premenstrual dysphoric disorder (PMDD) and a history of sexual abuse showed a greater FT3/FT4 ratio, as compared to women with PMDD and no history of sexual abuse as well as healthy controls. Friedman, Wang, Jalowiec, McHugo, and McDonagh-Coyle (2005) found significant elevations in TT3/FT4 and a significant reduction in TSH, in a community sample of 63 women with PTSD due to childhood sexual abuse as compared to 42 women without PTSD, of whom 17% also reported childhood sexual abuse.\nAs summarized in a report by Wang (2006), elevated T3 levels have earlier been reported in Vietnam, Israeli, World War II and Croatian combat veteran samples with PTSD. Studies of Vietnam veterans have reported elevated FT3/FT4 and TT3/FT4 ratios, in participants with PTSD, as compared to the non-PTSD group (Mason et al., 1994; Wang \u0026 Mason, 1999). In our study, levels of FT3 and FT3/FT4 ratio were higher, though not statistically significant in the comorbid PTSD group, as compared to the non-PTSD group.\nThere may be several reasons for the differences between the studies. First and foremost, the study populations differed with respect to gender, age and diagnosis. Secondly, the type, timing and duration of trauma exposure differed between the studies. The experience of stress elicits certain neurobiological mechanisms of in the HPT axis, with an increase of free thyroid hormones in the serum in conjunction with an increase of excretion via urine, leaving serum thyroid levels unchanged (Habermann et al., 1978) or within reference interval. KIVS measures different types of interpersonal violence including sexual violence. The nature of the trauma (physical or neglect), traumatic duration, setting of trauma, timing (i.e., stress exposure during certain developmental stages of the brain), and multiplicity of childhood traumata may evoke different mechanisms of stress regulation. Since the KIVS focus on interpersonal violence, neglect was not assessed in this present study. Longitudinal studies with stratification of traumatic exposure are sparse.\nSevere and prolonged traumatic stress may expose the body and brain to physiological burdens in the stress-response systems at the level of both neurotransmitters as well as neuroendocrine interactions, leaving either permanent changes or shifting the body metabolism from homeostasis, into allostasis; a new adaptive physiological or behavioral state, maybe through epigenetic mechanisms. The impact of severe trauma may be likened to an allostatic overload, forcing the individual to adapt to new hormonal set points, in order to survive the demanding environment. This may be reflected in altered hormonal levels within normal reference ranges. Moreover, processes not contingent of thyroid hormone levels may have effect on regulation on thyroid hormone levels among individuals (Costa-e-Sousa \u0026 Hollenberg, 2012). These processes may include genetically determined tissue specific local deiodination and cell membrane thyroid hormone transport, genetic variation in Type 1 iodothyronine deiodinase (Dayan \u0026 Panicker, 2009), as well as neuronal circuitries of energy regulatory pathways in the HPT axis of higher order than the negative feedback system.\nInterestingly, in the current study the cortisol levels were higher in women with PTSD. This may be in line with earlier studies indicating a dysregulation of HPA-axis in persons with PTSD (Meewisse et al., 2007). However, the high cortisol levels may also be the result of severity of BPD, comorbid depression, or the interaction between PTSD and BPD. In addition, individuals with BPD have been suggested to express hypercortisolemia in analogy with major depressive states (Zimmerman \u0026 Choi-Kain, 2009). We observed a weak but statistically significant relationship between sample storage time and FT3; therefore, we adjusted for sample storage time in the final regression model. However, the timing of blood sampling did not have a significant effect on hormone levels.\nAmong the limitations of this study is the cross-sectional study design, which prevents us from drawing casual conclusions. As the great majority of the patients were suffering from depression and had a history of severe suicidal behavior, we could not assess if the hormone levels were associated specifically to the depressive state or to the suicidal behavior. However, there were no significant differences in frequencies of antidepressants in different exposure groups. It is also worth mentioning that the study sample may not be representative of all BPD patients due to the specific selection criteria (i.e., history of at least two suicide attempts). Since the study was originally designed as a psychotherapy treatment study, it may be regarded as a convenience sample. Unfortunately, we did not have data of whether the women were in either luteal of follicular phase, which can be regarded as a limitation. Furthermore, three patients were taking lithium that is known to affect the thyroid hormone levels.\nThe strength of this study is the relatively large sample of women with thoroughly assessed DSM diagnosis of BPD. Furthermore, the study population is relatively homogenous with regard to age, gender, diagnosis and history of suicidal behavior, which should have lowered the variance due to unique adaptive metabolic mechanisms between individuals.\nIn summary, we found a negative relationship between exposure to interpersonal violence in childhood and the FT3/FT4, among 92 women with BPD. Comorbid diagnosis of PTSD was related to a more pronounced neuroendocrine dysregulation. It would be of great value to observe thyroid hormone changes in future longitudinal studies comprising individuals with and without PTSD, in order to capture time-related neuroendocrine variability."}