Money talks: performance-based reimbursement systems impact on perceived work, health and patient care for physicians in Sweden.

Introduction: The study aimed to investigate in which way performance-based reimbursement (PBR) systems in Swedish healthcare services (1) subjectively impacted physicians' work and patient care and (2) were associated with the occurrence of stress-induced exhaustion disorders among physicians. Method: The study applied a mixed-method design. Data were collected from a representative sample of Swedish physicians. In the questionnaire, respondents were asked to answer an open-ended question regarding their reflections on PBR. The answers to the open-ended question were analysed using thematic analysis. Respondents were also asked to rate the impact of PBR on their work. The association between PBR and self-rated stress-induced exhaustion disease was analysed with logistic regressions. Stress-induced exhaustion disorder was measured using the Burnout Assessment Scale. Results: Thematic analysis resulted in four themes: (1) Money talks, (2) Patients are affected, (3) Medical morals are challenged, and (4) PBR increase the quantity of illegitimate tasks. Logistic regressions showed that physicians who experienced PBR had an impact on their work and had a two-fold higher risk of stress-induced exhaustion disorder. Discussion: Our findings suggest that current reimbursement systems in Sweden play an essential role in Swedish healthcare and negatively influence physicians' work and health. Also, current PBR impact patients negatively. No previous study has explored the potentially harmful impact of PBR on how physicians perceive work, health and patient care. Results indicate that policymakers should be encouraged to deeply review PBR systems and focus on ways that they can limit the negative impact on physicians' work and health while meeting future challenges.

Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts.

Emotional unstable personality disorder (EUPD; previously borderline personality disorder, BPD) is associated with excess natural-cause mortality, comorbid medical conditions, poor health habits and stress related epigenomic alterations. Previous studies demonstrated that GrimAge - a state-of-the-art epigenetic age (EA) estimator - strongly predicts mortality risk and physiological dysregulation. Herein, we utilize the GrimAge algorithm to investigate whether women with EUPD and a history of recent suicide attempts exhibit EA acceleration (EAA) in comparison to healthy controls. Genome-wide methylation patterns were measured using the Illumina Infinum Methylation Epic BeadChip in whole blood from 97 EUPD patients and 32 healthy controls. The control group was significantly older (p < 0.0001) and reported lesser exposure to violent behavior in both youth and adulthood (p < 0.0001). Groups were otherwise comparable regarding gender, BMI, or tobacco usage (p > 0.05). EA estimator DNAmGrimAge exceeded chronological age by 8.8 and 2.3 years in the EUPD and control group, respectively. Similarly, EAA marker AgeAccelGrim was substantially higher in EUPD subjects when compared to controls, in both univariate and multivariate analyzes (p < 0.00001). Tobacco usage conferred substantial within-group effects on the EA-chronological age difference, i.e., 10.74 years (SD = 4.19) compared to 6.00 years (SD = 3.10) in the non-user EUPD group (p < 0.00001). Notably, past alcohol and substance abuse, use of psychotropic medications, global assessment of functioning, self-reported exposure to violent behavior in youth and adulthood, later completed suicide (N = 8) and age at first suicide attempt did not predict EAA in the EUPD group (p > 0.05). These results underscore the importance of addressing medical health conditions along with low-cost preventative interventions aimed at improving somatic health outcomes in EUPD, such as efforts to support cessation of tobacco use. The independency of GrimAge to other EA algorithms in this group of severely impaired EUPD patients, suggest it may have unique characteristics to evaluate risk of adverse health outcomes in context of psychiatric disorders.

Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women.

Brain-derived neurotrophic factor (BDNF) has previously been associated with the pathogenesis of both emotionally unstable personality disorder (EUPD) and suicidal behavior. No study has yet investigated BDNF-associated epigenetic alterations in a group of severely impaired EUPD and suicidal patients. The discovery cohort consisted of 97 women with emotionally unstable personality disorder (EUPD) with at least two serious suicide attempts (SAs) and 32 healthy female controls. The genome-wide methylation pattern was measured by the Illumina EPIC BeadChip and analyzed by robust linear regression models to investigate mean BDNF methylation levels in a targeted analysis conditioned upon severity of suicide attempt. The validation cohort encompassed 60 female suicide attempters, stratified into low- (n = 45) and high-risk groups (n = 15) based on degree of intent-to-die and lethality of SA method, and occurrence of death-by-suicide at follow-up. Mean BDNF methylation levels exhibited increased methylation in relation to EUPD (p = 0.0159, percentage mean group difference ~3.8%). Similarly, this locus was confirmed as higher-methylated in an independent cohort of females with severe suicidal behavior (p = 0.0300). Results were independent of age and BMI. This is the first study to reveal emerging evidence of epigenetic dysregulation of BDNF with dependence on features known to confer increased risk of suicide deaths (lethality of suicide-attempt method and presence of EUPD diagnosis with history of recent SAs). Further studies investigating epigenetic and genetic effects of BDNF on severe suicidal behavior and EUPD are needed to further elucidate the role of epigenetic regulatory mechanisms and neurotrophic factors in relation to suicide and EUPD, and hold potential to result in novel treatment methods.

Plasma levels of S100B and neurofilament light chain protein in stress-related mental disorders.

The pathophysiological changes underlying stress-related mental disorders remain unclear. However, research suggests that alterations in astrocytes and neurons may be involved. This study examined potential peripheral markers of such alterations, including S100B and neurofilament light chain (NF-L). We compared plasma levels of S100B and NF-L in patients with chronic stress-induced exhaustion disorder (SED), patients with major depressive disorder (MDD), and healthy controls. We also investigated whether levels of S100B and NF-L correlated with levels of astrocyte-derived extracellular vesicles (EVs that indicate astrocyte activation or apoptosis) and with symptom severity. Only women had measurable levels of S100B. Women with SED had higher plasma levels of S100B than women with MDD (P < 0.001) and healthy controls (P < 0.001). Self-rated symptoms of cognitive failures were positively correlated with levels of S100B (rs = 0.434, P = 0.005) as were depressive symptoms (rs = 0.319, P < 0.001). Plasma levels of astrocyte-derived EVs were correlated with levels of S100B (rs = 0.464, P < 0.001). Plasma levels of NF-L did not differ between the groups and were not correlated with symptom severity or EV levels. Thus, long-term stress without sufficient recovery and SED may be associated with raised plasma levels of S100B, which may be evidence of pathophysiological changes in astrocytes. The findings also support the hypothesis that plasma levels of S100B are associated with cognitive dysfunction.

The Swedish HealthPhys Study: Study Description and Prevalence of Clinical Burnout and Major Depression among Physicians.

Objectives: The study purpose was to describe the Swedish HealthPhys cohort. Using data from the HealthPhys study, we aimed to describe the prevalence of clinical burnout and major depression in a representative sample of Swedish physicians across gender, age, worksite, hierarchical position, and speciality in spring of 2021, during the third wave of the Covid-19 pandemic. Method: The HealthPhys questionnaire was sent to a representative sample of practising physicians (n = 6699) in Sweden in February to May of 2021 with a 41.3% response rate. The questionnaire included validated instruments measuring psychosocial work environment and health including measurements for major depression and clinical burnout. Results: Data from the HealthPhys study showed that among practising physicians in Sweden the prevalence of major depression was 4.8% and clinical burnout was 4.7%. However, the variations across sub-groups of physicians regarding major depression ranged from 0% to 10.1%. For clinical burnout estimates ranged from 1.3% to 14.5%. Emergency physicians had the highest levels of clinical burnout while they had 0% prevalence of major depression. Prevalence of exhaustion was high across all groups of physicians with physicians working in emergency departments, at the highest (28.6%) and anaesthesiologist at the lowest (5.6%). Junior physicians had high levels across all measurements. Conclusions: In conclusion, the first data collection from the HealthPhys study showed that the prevalence of major depression and clinical burnout varies across genders, age, hierarchical position, worksite, and specialty. Moreover, many practising physicians in Sweden experienced exhaustion and were at high risk of burnout.

Impaired cognitive functioning in stress-induced exhaustion disorder: a new tablet-based assessment.

BACKGROUND: The adverse health effects of stress induced exhaustion disorder (SED) cause increasing concern in Western societies. This disorder is characterized by severe fatigue, decreased tolerance to further stress, and attention and memory lapses. Despite subjective complaints, individual cognitive deficits are not always detected in a clinical setting, which calls for the validation of more sensitive instruments. AIM: The objective of this study was to investigate if a short, tablet-based serial naming task, MapCog Spectra (MCS) could be used as a marker for cognitive problems in SED. PARTICIPANTS: The study comprised of 39 subjects (35 females, four males) with SED. Their mean age was 46,8 years (SD 10.1; range 30-60 yrs.). All participants were healthcare professionals, with a college or university degree, doctors, registered nurses, and psychologists. METHODS: The MCS was used to assess the number of aberrant pauses during serial naming of coloured geometrical shapes. The Coding, Matrix Reasoning, Digit Span, Symbol Search of the WAIS-IV, and RUFF 2&7 tests, were administered together with a short interview. RESULTS: Mean values were within normal reference limits for all tests, except for the MCS, which showed a significantly higher number of aberrant pauses (p < 0,001) in the SED group, compared to normal reference values. Although subjects performed within normal limits on the RUFF 2&7, a significant difference between individuals was found in the performance strategy of the participants. CONCLUSION: Here we report that subjects with SED have performance deficits on the MCS, in terms of aberrant pause times, despite average performance on WAIS-IV tests measuring inductive reasoning, processing speed, working memory, and attention. We also demonstrate that subjects use different strategies to overcome their problems. These findings add to the growing evidence of cognitive deficits in SED and that the MCS might aid neuropsychologists in disentangling cognitive markers, important to substantiate the subjective complaints of affected individuals.

Isoforms of soluble vascular endothelial growth factor in stress-related mental disorders: a cross-sectional study.

Vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of stress-related mental disorders. However, VEGF levels have seldom been compared across mental disorders and never by isoforms. Pathophysiological processes involving leakage of astrocyte-derived extracellular vesicles (EVs) across the blood-brain barrier could be associated with VEGF levels in patients with stress-related mental disorders. This cross-sectional study compared plasma levels of VEGF121, VEGF165, and VEGF121 + VEGF165 (VEGFtotal) in patients with stress-induced exhaustion disorder (SED) (n = 31), patients with major depressive disorder (MDD) (n = 31), and healthy controls (n = 61). It also analyzed the correlation between VEGF and astrocyte-derived EVs in plasma. An enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF121 and VEGF165 in citrate plasma, and flow cytometry was used to measure astrocyte-derived EVs in plasma. The mean concentration of soluble VEGF121 (sVEGF121) was significantly higher in patients with SED than healthy controls (P = 0.043). Mean sVEGF165 was significantly lower in patients with MDD than patients with SED (P = 0.004) or healthy controls (P = 0.037). Mean sVEGFtotal was significantly higher in patients with SED than in patients with MDD (P = 0.021) and also higher in patients with SED than healthy controls (P = 0.040). Levels of sVEGF121 were positively correlated with levels of astrocyte-derived EVs only in patients with SED (P = 0.0128). The same was true of levels of sVEGFtotal and astrocyte-derived EVs (P = 0.0046). Differing levels of VEGF isoforms may reflect different pathophysiological mechanisms in SED and MDD. Further research is needed to better understand the potential roles of VEGF isoforms and astrocyte-derived EVs in mental disorders.

Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study.

Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-derived EVs could be higher in patients with SED than in patients with major depressive disorder (MDD) and healthy controls. Patients with SED (n = 31), MDD (n = 31), and healthy matched controls (n = 61) were included. Astrocyte-derived EVs (previously known as microparticles) were measured in plasma with flow cytometry and labeled against glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4). In addition, platelet EVs and their CD40 ligand expression were measured. Patients with SED had significantly higher concentrations of AQP4 and GFAP-positive EVs and EVs co-expressing AQP4/GFAP than patients with MDD and healthy controls. Patients with MDD had significantly higher concentrations of GFAP-positive EVs and EVs co-expressing AQP4/GFAP than healthy controls. Platelet EVs did not differ between groups. CD40 ligand expression was significantly higher in patients with SED and MDD than in controls. In conclusion, the present study suggests that patients with SED, and to some extent, patients with MDD, have increased leakage of astrocyte-derived EVs through the blood-brain barrier.

Exposure to interpersonal violence and risk of post-traumatic stress disorder among women with borderline personality disorder.

BACKGROUND: This study aims to determine the validity of the Karolinska Interpersonal Violence Scale (KIVS), as a screening tool for PTSD, among women with borderline personality disorder (BPD) and severe suicidal behavior. METHOD: 106 women with BPD and at least two suicide attempts were assessed with the KIVS for exposure to interpersonal violence as a child and as an adult. The screening ability of the KIVS for the diagnosis of PTSD was analyzed using receiver operating characteristic curve analysis. RESULTS: PTSD diagnosis was valid for 61 (58%) women with BPD. The KIVS - exposure of lifetime interpersonal violence, displayed fair accuracy of predicting diagnosis of PTSD (area under the curve 0.79, confidence interval [0.71, 0.88]) and performed well (sensitivity 0.90 and specificity 0.62), with a cut-off score of 4 (range 0-10). Poly-traumatization was not significantly related to PTSD diagnosis as compared to single traumatization, whereas sexual victimization was significantly more prevalent in women with PTSD diagnosis, as compared to other types of traumatic events. CONCLUSION: A score of 4 or more on the KIVS - exposure to interpersonal lifetime violence presents well as a screening instrument for risk of PTSD, among women with BPD.

Clinical severity as a moderator of outcome in psychodynamic and dialectical behavior therapies for borderline personality disorder.

The aim of the present study was to assess the effect of initial level of psychiatric severity on treatment outcome in psychodynamic therapy and dialectical behavior therapy (DBT) for borderline personality disorder (BPD). It was hypothesized that DBT would lead to better outcome for patients with high psychiatric severity, whereas dynamic treatment would lead to better outcome for patients with lower psychiatric severity. Data from the 5th-year follow-up of the Stockholm City Council's and the Karolinska Institute's Psychotherapy Project were used in the present study. A total of 106 female patients diagnosed with BPD with at least 2 past suicide attempts were randomized into object-relational psychotherapy (ORP; based on transference-focused psychotherapy), DBT, and treatment as usual. Patients' baseline global severity index was used as a moderator. Global Assessment of Functioning (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [American Psychiatric Association, 1994]) was used to examine outcome. There was a significant 3-way interaction of Time × Treatment × Severity. Post hoc analyses suggested that patients with lower levels of severity had significantly better outcomes in object-relational psychotherapy. For patients with higher severity, the 3 treatments resulted in similar outcomes in terms of level of functioning. Outcome of treatment for BPD might differ significantly for patients depending on their initial levels of overall psychiatric severity. If our findings are replicated for patients with low severity and supported for a high-severity sample, psychiatric severity can be used as a low-cost and effective tool to match patients with BPD to optimal treatments. (PsycINFO Database Record

Psychodynamic profile and reflective functioning in patients with bulimia nervosa.

OBJECTIVE: The aim of this study was to examine the general psychological functioning of patients suffering from bulimia nervosa (BN) using the Karolinska Psychodynamic Profile (KAPP). Furthermore, KAPP data and data from the Reflective Functioning scale (RF), measuring the ability to mentalize, were combined in order to examine differences in alexithymia, impulse control and affect regulation in patients with high or low RF. METHOD: Seventy patients with BN were interviewed with both the KAPP and the Adult Attachment Interview (AAI) from which RF is coded. Differences in KAPP scores of patients with high or low RF were analyzed. RESULTS: Most of the patients with BN were found to have a personality structure within the normal or neurotic range (n=50 of 70). BN patients with a high RF had significantly lower scores on KAPP's alexithymia scale than patients with a low RF score, demonstrating that poor mentalizing is related to alexithymia. Concurrently, patients with high RF showed problems with impulse control and coping with aggressive affects according to KAPP scores. CONCLUSION: Although BN patients with high RF showed good capacities for describing their mental states, they still had difficulties regulating the emotions and impulses related to these states. SIGNIFICANT OUTCOME: Among patients suffering from BN, patients with high RF were significantly less alexithymic than low RF patients. LIMITATIONS: The findings of this study are limited by the relatively small numbers of participants especially in the RF subgroups, posing a danger of not finding as significant existing differences in character pathology between high and low RF groups.

Thyroid hormones and adult interpersonal violence among women with borderline personality disorder.

Elevated T3 levels have been reported in men with antisocial behavior. The aim of the present study was to investigate the relationship between thyroid hormones and expressed adult interpersonal violence in female patients with borderline personality disorder (BPD). Furthermore, expressed adult interpersonal violence in female BPD patients was compared to healthy female controls. A total of 92 clinically euthyroid women with BPD and 57 healthy women were assessed with the Karolinska Interpersonal Violence Scales (KIVS). Baseline thyroid function was evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3), thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays in patients. Plasma cortisol was also measured. Among females with BPD, expressed interpersonal violence as an adult showed a significant positive correlation with the T3 levels. The mean expression of interpersonal violence as an adult was significantly higher in BPD patients as compared to healthy controls. The multiple regression model indicated that two independent predictors of KIVS expressed interpersonal violence as an adult: T3 and comorbid diagnosis of alcohol abuse. Association between T3 levels and violent/aggressive behavior earlier reported exclusively in male samples may be valid also in females with BPD.

Karolinska Psychodynamic Profile for Sexual Disorders: KAPP-SD. A proposal for a psychodynamic rating scale for sexual disorders.

OBJECTIVE: Our first objective in this paper was to review the literature on psychodynamic rating scales of sexual disorders. Our second objective, based on the findings from our review, was to develop a psychodynamic rating scale for people with sexual disorders: the KAPP-SD. METHOD: We developed the KAPP-SD by modifying an existing psychodynamic rating scale, which assesses stable modes of mental functioning and character traits, the Karolinska Psychodynamic Profile (KAPP). We removed items 13 and 14 of the KAPP and replaced them with three other items-sexual fantasies, conceptions and role of gender identity, and conceptions and role of sexual orientation. These items are part of the assessment of an individual's sexuality and are used to evaluate a person with a sexual disorder psychodynamically. RESULTS: The KAPP-SD, a modified version of the KAPP, can be found in the Appendix. CONCLUSION: We developed the KAPP-SD in order to help sex therapists make a rigorous psychodynamic evaluation of persons with sexual disorders, which would give information on the prognosis and on the type of treatment to offer.

Hypothalamic pituitary thyroid axis and exposure to interpersonal violence in childhood among women with borderline personality disorder.

BACKGROUND: A relationship between exposure to sexual violence and thyroid hormone alterations has been observed among women with posttraumatic stress disorder (PTSD). Women with borderline personality disorder (BPD) report a high estimate of childhood trauma. OBJECTIVE: The aim of the present study was to assess relationships between thyroid hormone measures and exposure to violence in childhood in women with BPD. METHOD: A total of 92 clinically euthyroid women with BPD (53% with comorbid PTSD) diagnosis and at least two prior suicide attempts were assessed with the Karolinska Interpersonal Violence Scales (KIVS). The KIVS contains four subscales 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). Baseline thyroid function was evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3), thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays. The FT3/FT4 ratio was used to estimate peripheral deiodination. Plasma cortisol was also assessed. RESULTS: Sixty-seven percent of patients reported medium high or high level of exposure to interpersonal violence as a child. The FT3/FT4 ratio showed a significant negative correlation with exposure to violence as a child. Patients with PTSD had significantly higher plasma cortisol levels. An ad hoc analysis revealed that the correlation between KIVS exposure to interpersonal violence as a child and FT3/FT4 ratio was significant only in patients with comorbid PTSD. Altered thyroid activity, especially FT3/FT4, levels was associated with exposure to violence in childhood in women with BPD. CONCLUSION: Severe childhood trauma-related stress may promote lasting altered thyroid levels and/or contribute to the development of psychopathology associated with BPD traits or PTSD.

Shame-proneness in attempted suicide patients.

BACKGROUND: It has been suggested that shame may be an important feature in suicidal behaviors. The disposition to react with shame, "shame-proneness", has previously not been investigated in groups of attempted suicide patients. We examined shame-proneness in two groups of attempted suicide patients, one group of non-suicidal patients and one group of healthy controls. We hypothesized that the attempted suicide patients would be more shame-prone than non-suicidal patients and healthy controls. METHODS: The Test of Self-Conscious Affect (TOSCA), which is the most used measure of shame-proneness, was completed by attempted suicide patients (n = 175: 105 women and 3 men with borderline personality disorder [BPD], 45 women and 22 men without BPD), non-suicidal psychiatric patients (n = 162), and healthy controls (n = 161). The participants were convenience samples, with patients from three clinical research projects and healthy controls from a fourth research project. The relationship between shame-proneness and attempted suicide was studied with group comparisons and multiple regressions. Men and women were analyzed separately. RESULTS: Women were generally more shame-prone than men of the same participant group. Female suicide attempters with BPD were significantly more shame-prone than both female suicide attempters without BPD and female non-suicidal patients and controls. Male suicide attempters without BPD were significantly less shame-prone than non-suicidal male patients. In multiple regressions, shame-proneness was predicted by level of depression and BPD (but not by attempted suicide) in female patients, and level of depression and non-suicidality in male patients. CONCLUSIONS: Contrary to our hypothesis and related previous research, there was no general relationship between shame-proneness and attempted suicide. Shame-proneness was differentially related to attempted suicide in different groups of suicide attempters, with significantly high shame-proneness among female suicide attempters with BPD and a negative relationship between shame-proneness and attempted suicide among male patients. More research on state and trait shame in different groups of suicidal individuals seems clinically relevant.