@misc{Krupa_Anna_Factors_2024,
 author={Krupa, Anna},
 address={Kraków},
 howpublished={online},
 year={2024},
 school={Rada Dyscypliny Nauki medyczne},
 language={pol; eng},
 abstract={Introduction Fibromyalgia (FM) is a syndrome which manifests primarily as chronic, generalized pain, accompanied also by other symptoms such as fatigue, sleep disturbances, cognitive impairment or depression. These symptoms significantly impair the patients’ functioning in the fundamental domains of everyday tasks, family and social relationships, work and cause a significant loss of the quality of life. As indicated by epidemiological data, FM impacts 2–4% of the general population. The FM diagnosis is based on symptomatic criteria, currently the criteria which offer the highest sensitivity and specificity are those proposed by the American College of Rheumatology (ACR) and revised in 2016. Unfortunately, despite the rather high prevalence of FM, the present-day knowledge on its etiopathogenesis is far form satisfactory and does not suffice to create a comprehensive description thereof. Moreover, there are no biomarkers or objective tests, which would allow for the verification of FM diagnosis, that is based primarily on the physician’s history-taking and fulfillment of criteria. Furthermore, FM is not a diagnosis of exclusion, it may coexist with other disorders. Additionally, some authors differentiate between primary (when no other pathologies are present i.e. rheumatologic or pain disorders) and secondary FM (in the case of comorbidity with other disorders i.e. rheumatolog},
 abstract={ic or pain-related). As a result, the group of FM patients, which is selected according to the symptom-based criteria, is heterogeneous with regard to the biological underpinnings of its symptoms, clinical presentation and susceptibility to treatment. Regrettably, previous studies conducted in the FM group did not differentiate subtypes of this clinical condition that would be more homogenous in terms of underlying biology or clinical manifestation. Hence, the FM treatment is symptomatic and characterized by limited, often unsatisfactory effectiveness. The most recent FM treatment guidelines recommend the multimodal care, which is principally based on non-pharmacological interventions: physical activity, cognitive–behavioral or mindfulness psychotherapy, physical therapies among others. However, the effects of these non-pharmacological therapies are often not sufficient and pharmacological treatment has to be introduced. The drugs, which effectiveness in reduction of FM symptoms is most robustly supported by scientific evidence, are the selective serotonin and noradrenaline reuptake inhibitors (SNRI) and pregabalin. Incidentally, these medicines are widely used in the treatment of depression (SNRI) and anxiety. In accordance with the recommendations proposed by the working group Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) the cut-off va},
 abstract={lues for clinically significant treatment effects in FM are 30% and 50% pain reduction which translates to moderate and substantial clinical improvement. Formerly published works on the etiopathogenesis of FM indicated the significance of genetics, mechanisms linked to central sensitization, neurogenic inflammation, small-fiber neuropathy, autoimmunization, gut microbiota dysregulation, oxidative stress as well as sleep and diurnal rhythm disturbances. Recently published works have also suggested impaired glucose metabolism, as well as insulin resistance in FM and it was shown in animal studies that antidiabetic drug (pioglitazone) reduces the severity of FM symptoms. Also, the preliminary analyses of data this study’s data revealed the presence of insulin resistance in FM, however they indicated that it only concerns a subset of patients. The comorbid mental problems remain a burning issue of FM treatment. In FM patients vs. subjects without FM, the lifetime prevalence of anxiety and depression disorders is 3–4 times higher, post-traumatic stress disorder 6 times higher and bipolar disease over 7 times higher. It was shown that the severity of affective symptoms and/or anxiety is significantly associated with FM severity and its influence of patients functioning. Moreover, it was indicated that dissociative symptoms are more pronounced in subjects with FM vs. those with rheuma},
 abstract={tic disorders or healthy controls, also a relationship between dissociative symptoms and FM clinical presentation was described. Before the publication of initial analyses of this study, no earlier works explored the severity anhedonia in this patient group and/or the role of psychopathological dimensions in the effectiveness of treatment. The research evaluating the association between such psychological variables as temperament, personality or schizotypy and clinical presentation of FM is also scarce. Single articles have highlighted, that some temperamental features are linked to the severity of FM and comorbid depression as well as anxiety and that some personality traits are related to the level of pain, FM symptoms, depression, anxiety, and patient functioning. No works assessing the severity of schizotypy in FM are available. What is more, no data were published, which would examine the relationships between the above-mentioned psychological variables and the effects of FM pharmacotherapy. Objectives The main objective of this study was to verify the hypothesis about the differences in the glucose metabolism, insulin resistance, severity of psychopathological symptoms and psychological variables in FM patients responsive to SNRI treatment (FM T[+]) and nonresponsive to SNRI treatment (FM T[-]). The additional goal was to also conduct the comparisons of glucose metabolism},
 abstract={, insulin resistance, severity of psychopathological symptoms and psychological variables in FM patients (as a whole group and with the distinction of subgroups responsive or non-responsive to SNRI treatment) and healthy controls. Consequent steps were conducted to facilitate these objectives: 1. The assessment, carried out in the whole FM group and with the distinction of subgroups FM T[+] and FM T[-] as well as in (healthy controls – HC), of variables listed below: a) FM clinical presentation (only in FM subjects) b) glucose metabolism and insulin resistance c) presence of psychopathological symptoms (depressive, anxious, anhedonia, bipolar spectrum, dissociative), d) level of psychological variables (traits of affective temperament, personality and schizotypy), 2. The comparisons between FM as a whole group and HC as well as comparisons with the distinction of subgroups FM T [+], FM T [-], HC in the aspects of: a) Variables linked to glucose metabolism and insulin resistance b) Severity of psychopathological symptoms and frequency of results indicating the level of symptoms of clinical importance (depressive, anxious, anhedonia, bipolar spectrum, dissociative), c) Levels of psychological variables (traits of affective temperament, personality and schizotypy), 3. Evaluation of the links between the above-mentioned aspects and the presence of treatment response to SNRI in FM M},
 abstract={ethods Participants were recruited from the patients of inpatient and outpatient wards of the Psychiatry Department for Adults and Department of Rheumatology and Immunology, Psychiatry Outpatient Department for Adults and Rheumatology Outpatient Department of the University Hospital in Krakow. All participants underwent the drawing of blood samples, which were evaluated for the level of fasting glucose and insulin, based on which the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) value was calculated. Subjects were examined by a physician (psychiatrist in the course of specialty training in adult psychiatry; that is the Author of this thesis) and completed self-assessment questionnaires which verified the clinical presentation of FM, severity of psychopathological symptoms and psychological variables. In order to distinguish the FM T[+] or FM T[-] patients were asked to report the severity of the pain on the Numerical Rating Scale (NRS) ranging 0–10 (with 0 meaning no pain and 10 meaning highest pain severity) and the change after at least 8 weeks of SNRI treatment was calculated by the subtraction of “post” vs. “pretreatment” NRS scores; change size ranged from 0 (no change in pain severity) to 10 (complete pain relief). Based on the IMMPACT recommendations, the treatment response to SNRI was defined as at least 30% pain relief (that is no less than: 3 points in},
 abstract={case of initial NRS score 7–10; no less than 2 in case of initial NRS score 4–6). Next appropriate statistical methods were applied to assess the relationships between FM clinical presentation, metabolic variables, psychopathological symptoms, psychological variables and response to SNRI in FM. Results 62 subjects FM and 30 HC were included in this study. FM patients were divided into subgroups of FM T[+] n = 30 and FM T[-] n = 32. All groups were comparable regarding sex and comorbid disorders. 1. The f i r s t article explored the associations between metabolic variables, psychiatric comorbidity and response to SNRI pharmacotherapy, showing that: a) FM T[-] subjects were characterized by higher symptom severity and influence of FM on their functioning than FM T[+], b) the whole FM group compared to HC showed higher scores of some but not all metabolic variables, c) FM T[+] participants had similar levels of metabolic variables compared to HC, while FM T[-] presented higher scores of fasting glucose and insulin as well as HOMA-IR values than HC and FM T[+], moreover fasting glucose levels were significantly higher among FM T[-] vs. FM T[+] (no significant differences in fasting glucose were noted between FM T[-] and HC), d) the percentages of FM patients diagnosed with depressive, anxiety or personality disorders were higher among FM T[-] than FM T[+], e) insulin resistance, d},
 abstract={epressive, anxiety or personality disorders were the predictive factors of lack of response to SNRI in FM. 2. The s e c o n d work examined the severity of psychopathological symptoms of: depression, anxiety, bipolar spectrum, anhedonia and dissociation in FM and their relationships with response to SNRI treatment, noting that: a) FM T[-] patients presented higher overall severity of FM and its severity in the domains of physical functioning, well-being, work, pain, fatigue/sleep, b) in the aspect of the analyzed continuous variables FM T[-] subjects vs. FM T[+] were characterized by: higher severity of depression, state and trait anxiety and anhedonia, data regarding the bipolar spectrum were conflicting (the Mood Disorder Questionnaire [MDQ] results indicating higher number of these symptoms in FM T[-], Hypomania Checklist [HCL] not), no differences were noted in the severity of dissociative symptoms between FM T[+] and FM T[-], c) with regard to the analyzed dichotomous variables FM T[-] participants vs. FM T[+]: more often reported the severity of anxiety above the cut-off for clinical levels, while the results concerning the frequency of subjects reporting clinical levels of depression and bipolar spectrum symptoms were incoherent (the results of Quick Inventory of Depressive Symptomatology [QIDS] and MDQ suggested higher frequency of participants reporting symptoms above},
 abstract={the cut-off for clinical level in FM T[-] vs. FM T[+], on the other hand the results of Hospital Anxiety and Depression Scale depression subscale [HADS-D] and HCL did not show significant differences between groups), moreover, no differences were observed in the frequency of reported anhedonia or dissociative symptoms above the cutoff for clinical severity between FM T[-] and FM T[+], d) in the aspects of continuous variables: among the whole FM group and subgroup of FM T[- ] the severity of depressive, anxiety, bipolar spectrum and dissociative symptoms was higher than among HC, however among FM T[+] subgroup only the severity of depressive and dissociative symptoms was higher than in HC (unclear results regarding the bipolar spectrum, some indicating higher number of symptoms in FM T[+] vs. HC, some not), e) with regard to the analyzed dichotomous variables FM as a whole group and FM T[-] participants vs. HC more often reported the severity of depressive, anxiety, anhedonia and bipolar spectrum symptoms exceeding the cut-off for clinical levels, however for the comparison between FM T[+] and HC the frequency of the reported severity of all studied symptoms above the cut-off of clinical severity was similar, f) higher levels of depression, anxiety and anhedonia were the predictive factors of the lack of response SNRI in FM. 3. The t h ir d work assessed the levels of affective},
 abstract={temperament traits, personality and schizotypy and their links to lack of response to SNRI pharmacotherapy in FM, indicating that: a) in comparison to FM T[+], FM T[-] subjects showed higher levels of irritable and anxious temperament, feature of neuroticism and cognitive disorganization as well as overall schizotypy, b) patients with FM as a whole group as well as both FM T[+] and FM T[-] subgroups vs. HC presented higher levels of depressive, cyclothymic and anxious temperaments, as well as overall schizotypy and its unusual experiences, cognitive disorganization, introvertive anhedonia and impulsive nonconformity subscales, while their levels of personality traits i.e. extraversion and emotional stability were lower c) higher levels of depressive, irritable and anxious temperaments, cognitive disorganization and overall schizotypy as well as lower extraversion and emotional stability were the predictive factors of lack of response to SNRI in FM. Conclusions The innovation of this study consists in its methodology, because this work was the first to assess FM subjects not only as a whole group but also with an a priori distinction of FM T[+] and FM T[-] subgroups. In contrast to the previous works, which examined FM as a homogenous group, this made it possible to show, that some metabolic abnormalities, psychiatric comorbidities and psychological variables characterize only},
 abstract={FM T[-] but not FM T[+]. First, it was noted that FM T[-] present impairments of glucose metabolism, insulin resistance and higher BMI compared to FM T[+] and HC. Furthermore, FM T[-] reported higher severity and of symptoms and impact of FM on their functioning and were more often burdened with depressive, anxiety or personality disorders than FM T[+]. Second, it was observed that the severity of some psychopathological variables, as well as the proportion of participants reporting clinical severity of particular psychopathological symptoms, are higher in FM T[-] than FM T[+]. Third, it was showed that FM T[-] subjects were characterized by higher levels of specific affective temperaments, personality traits and schizotypy vs. FM T[+]. Additionally, due to the study methodology, it was revealed that 1) the metabolic variable of insulin resistance, 2) being burdened with depression, anxiety or personality disorder, 3) severity of depression, anxiety and anhedonia, 4) levels of temperament features: depressive, irritable and anxious as well as schizotypy and its cognitive disorganization domain are positive predictors (meaning, they increase the risk) of lack of response to SNRI in, while the levels of 1) personality traits: extraversion and emotional stability is are negative predictors of lack of response to SNRI in FM. The obtained data allowed to reveal metabolic factors, ps},
 abstract={ychopathological symptoms and psychological variables linked to the lack of response to SNRI in FM. This knowledge might facilitate the development and optimalization as well as personalization of treatment for individuals with FM and help navigate the directions of future research of FM.},
 title={Factors associated with ineffectiveness of selective inhibitors of serotonin and noradrenalin in fibromyalgia treatment},
 type={Praca doktorska},
 keywords={fibromyalgia, depression, anxiety, insulin resistance, serotonin and noradrenaline reuptake inhibitors},
}