Inflammatory proteins and miRNA-144-5p in patients with depression, anxiety, or stress- and adjustment disorders after psychological treatment.

Both inflammatory proteins and microRNAs (miRNA) have been reported to be associated with various psychiatric disorders. However, the association between inflammatory proteins and miRNAs remains largely unknown, especially for patients with depression, anxiety, or stress- and adjustment disorders. In this study, we analyzed plasma levels of 92 inflammatory proteins from 178 patients with depression, anxiety, or stress- and adjustment disorders at baseline and after 8-week psychological treatments which resulted in a significant decrease in the Montgomery Åsberg Depression Rating Scale (MADRS-S) score. We investigated the response of the proteins after treatment and the correlation with miR-144-5p. After Benjamini-Hochberg correction for multiple testing, a total of 36 inflammatory proteins changed significantly after 8-week psychological treatments. Among the 36 significantly changed proteins, 21 proteins showed a decrease, and 17/21 proteins were inversely associated with plasma miR-144-5p levels at baseline. In addition, decreases in these proteins were associated with increases in miR-144-5p after treatment. The findings were similar after stratification by use of medications. The associations between the proteins and depression at baseline, measured by MADRS-S, as well as the change in protein levels and treatment response were, however, less clear. These findings need to be examined in future studies.

Risk of prostate cancer in relatives of prostate cancer patients in Sweden: A nationwide cohort study.

BACKGROUND: Evidence-based guidance for starting ages of screening for first-degree relatives (FDRs) of patients with prostate cancer (PCa) to prevent stage III/IV or fatal PCa is lacking in current PCa screening guidelines. We aimed to provide evidence for risk-adapted starting age of screening for relatives of patients with PCa. METHODS AND FINDINGS: In this register-based nationwide cohort study, all men (aged 0 to 96 years at baseline) residing in Sweden who were born after 1931 along with their fathers were included. During the follow-up (1958 to 2015) of 6,343,727 men, 88,999 were diagnosed with stage III/IV PCa or died of PCa. The outcomes were defined as the diagnosis of stage III/IV PCa or death due to PCa, stratified by age at diagnosis. Using 10-year cumulative risk curves, we calculated risk-adapted starting ages of screening for men with different constellations of family history of PCa. The 10-year cumulative risk of stage III/IV or fatal PCa in men at age 50 in the general population (a common recommended starting age of screening) was 0.2%. Men with ≥2 FDRs diagnosed with PCa reached this screening level at age 41 (95% confidence interval (CI): 39 to 44), i.e., 9 years earlier, when the youngest one was diagnosed before age 60; at age 43 (41 to 47), i.e., 7 years earlier, when ≥2 FDRs were diagnosed after age 59, which was similar to that of men with 1 FDR diagnosed before age 60 (41 to 45); and at age 45 (44 to 46), when 1 FDR was diagnosed at age 60 to 69 and 47 (46 to 47), when 1 FDR was diagnosed after age 69. We also calculated risk-adapted starting ages for other benchmark screening ages, such as 45, 55, and 60 years, and compared our findings with those in the guidelines. Study limitations include the lack of genetic data, information on lifestyle, and external validation. CONCLUSIONS: Our study provides practical information for risk-tailored starting ages of PCa screening based on nationwide cancer data with valid genealogical information. Our clinically relevant findings could be used for evidence-based personalized PCa screening guidance and supplement current PCa screening guidelines for relatives of patients with PCa.

Effect of mindfulness on physical activity in primary healthcare patients: a randomised controlled trial pilot study.

Increased physical activity can have health benefits among inactive individuals. In Sweden, the healthcare system uses physical activity on prescription (PAP) to motivate patients to increase their physical activity level. Mindfulness may further heighten the internal motivation to engage in physical activity. However, previous research has not demonstrated clear evidence of such an association. AIM: Examine the feasibility of the study design as a preparation for a full-scale study, and examine the differences, between three interventions, in change over time in physical activity levels and in related variables. METHOD: Comparison between three different interventions in an ordinary primary health care setting: PAP, mindfulness, and a combination of PAP and mindfulness. Physical activity was measured with self-report and ACTi Graph GT1X activity monitor. Statistical analysis was performed with a mixed-effect model to account for repeated observations and estimate differences both within groups and between groups at 3- and 6-months follow-up. RESULTS: Between September 2016 and December 2018, a total of 88 participants were randomised into three groups. The total dropout rate was 20.4%, the attendance rate to the mindfulness courses (52% > 6 times) and the web-based mindfulness training (8% > 800 min) was low according to the stated feasibility criteria. Eleven participants were excluded from analysis due to low activity monitor wear time. Neither the activity monitor data nor self-reported physical activity showed any significant differences between the groups. CONCLUSION: The study design needs adjustment for the mindfulness intervention design before a fully scaled study can be conducted. A combination of PAP and mindfulness may increase physical activity and self-rated health more than PAP or mindfulness alone. TRIAL REGISTRATION: ClinicalTrials.gov, registration number NCT02869854 . Regional Ethical Review Board in Lund registration number 2016/404.

Economic evaluation of mindfulness group therapy for patients with depression, anxiety, stress and adjustment disorders compared with treatment as usual.

BACKGROUND: A randomised controlled trial found that a structured mindfulness group therapy (MGT) programme was as effective as treatment as usual (mostly cognitive-behavioural therapy) for patients with a diagnosis of depression, anxiety or stress and adjustment disorders in Sweden (ClinicalTrials.gov: NCT01476371). AIMS: To perform a cost-effectiveness analysis of MGT compared with treatment as usual from both a healthcare and a societal perspective for the trial duration (8 weeks). METHOD: The costs from a healthcare perspective included treatment as usual, medication and costs for providing MGT. The societal perspective included costs from the healthcare perspective plus savings from productivity gains for the trial duration. The effectiveness was measured as quality-adjusted life-years (QALY) using the EQ-5D-5L questionnaire and the UK value set. Uncertainty surrounding the incremental costs and effects were estimated using non-parametric bootstrapping with 5000 replications and presented with 95% confidence intervals and cost-effectiveness acceptability curves. RESULTS: The MGT group had significantly lower healthcare and societal costs (mean differences -€115 (95% CI -193 to -36) and -€112 (95% CI -207 to -17), respectively) compared with the control group. In terms of effectiveness, there was no significant difference in QALY gain (mean difference -0.003, 95% CI -0.0076 to 0.0012) between the two groups. CONCLUSIONS: MGT is a cost-saving alternative to treatment as usual over the trial duration from both a healthcare and a societal perspective for patients with a diagnosis of depression, anxiety or stress and adjustment disorders in Sweden.

Long-term improvements after mindfulness-based group therapy of depression, anxiety and stress and adjustment disorders: A randomized controlled trial.

BACKGROUND: Although mindfulness-based group therapies (MGTs) for depressive, anxiety or stress and adjustment disorders are promising, there is a substantial lack of knowledge regarding the long-term improvements after such therapies in these common psychiatric disorders. METHODS: Two hundred and fifteen patients were randomized in a randomized clinical trial (RCT) (ClinicalTrials.gov ID: NCT01476371) conducted in 2012 at 16 primary healthcare centres in southern Sweden. The patients were randomized to MGT or treatment as usual (TAU) and completed four psychometric self-rated scales after 8 weeks of treatment. Approximately 12 months after the completion of the 8-week treatment, the same scales were repeated. Ordinal and generalized linear-mixed models, adjusted for cluster effects, were used for the analysis. RESULTS: For all four psychometric scales (MADRS-S [Montgomery-Åsberg Depression Rating Scale-S], HADS-D, HADS-A [Hospital Anxiety and Depression Scale A and D] and PHQ-9 [Patient Health Questionnaire-9]) the scores at the 1-year follow-up were significantly improved (all P values <0.001) in both groups. Furthermore, there were no significant differences between the MGT and TAU in the psychometric scores at the 1-year follow-up. CONCLUSIONS: To the best of our knowledge, this is the first RCT comparing the long-term improvements after MGT with TAU. Although it cannot be excluded that our findings are a result of the natural course of common psychiatric disorders or other factors, they suggest a long-term positive improvement after both MGT and TAU.

Pilot study on increased adherence to physical activity on prescription (PAP) through mindfulness: study protocol.

BACKGROUND: In the Swedish population aged between 50 and 64 years only 7.1% reach the recommended level of physical activity. Physical activity on prescription (PAP) has been used in Sweden since the beginning of the twenty-first century with moderate adherence of approximately 50%. Mindfulness seems to affect motivation to and satisfaction with physical activity. The aim is to test the feasibility of a study in routine care; i.e. to test if mindfulness can improve adherence to PAP, measured by changes in physical activity. METHODS/DESIGN: We will include 90 sedentary individuals, aged 40-65 years, from primary health care centres in Sweden. Individuals will be randomised to only PAP, mindfulness and PAP or mindfulness only. The PAP group will be based on patients' preferences. The mindfulness groups will meet once a week for 8 weeks and practise 20 min of individual training per day. There will not be any motivational interview or physical activity on prescription in the group assigned to only mindfulness. The participants will complete the Five Facet Mindfulness Questionnaire, the Insomnia Severity Index and also answer questions concerning their lifestyle. Physical activity will be measured by ACTi Graph GT1X activity monitor at baseline and after 3 and 6 months. Patients with a severe psychological disease, unstable angina or a recent myocardial infarction will be excluded. The main outcome will be adherence to PAP in an ordinary primary health care setting. In this pilot study, we will also evaluate measures such as the recruitment rate, number of dropouts and adherence to mindfulness practice. DISCUSSION: This study is the first to explore the effect of mindfulness on adherence to PAP and test the feasibility of the study design. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02869854 . Registered on 26 August 2016.

Macrophage Migration Inhibitory Factor and microRNA-451a in Response to Mindfulness-based Therapy or Treatment as Usual in Patients with Depression, Anxiety, or Stress and Adjustment Disorders.

Background: Macrophage migration inhibitory factor is a proinflammatory cytokine that has been associated with various psychiatric disorders. MicroRNA-451a can directly target macrophage migration inhibitory factor and downregulate its expression in cells. However, the role of macrophage migration inhibitory factor and microRNA-451a in psychiatric patients treated with psychotherapeutic interventions is unknown. In this study, our aim was to investigate levels of macrophage migration inhibitory factor and its regulating microRNA-451a in patients with depression, anxiety, or stress and adjustment disorders who underwent mindfulness-based therapy or treatment as usual. Methods: A total of 168 patients with psychiatric disorders were included from a randomized controlled trial that compared mindfulness-based therapy with treatment as usual. Plasma levels of macrophage migration inhibitory factor and microRNA-451a were measured at baseline and after the 8-week follow-up using Luminex assay and qPCR. Results: Macrophage migration inhibitory factor levels decreased significantly in patients posttreatment, whereas microRNA-451a levels showed a nonsignificant change. Macrophage migration inhibitory factor levels were inversely associated with microRNA-451a expression levels at baseline (ß=-0.04, P=.008). The change in macrophage migration inhibitory factor levels (follow-up levels minus baseline levels) was associated with the change in microRNA-451a (follow-up levels minus baseline levels) (ß=-0.06, P < .0001). The change in either macrophage migration inhibitory factor or microRNA-451a was not associated with improvement in psychiatric symptoms. Conclusion: We demonstrate that the levels of macrophage migration inhibitory factor decreased after psychotherapeutic interventions in patients with psychiatric disorders. However, this reduction was not associated with an improvement in psychiatric symptoms in response to the treatment. We also found an association between macrophage migration inhibitory factor and its regulating microRNA. However, this association needs to be further examined in future studies.

Yoga - a laborious way to well-being: patients' experiences of yoga as a treatment for hypertension in primary care.

OBJECTIVE: The aim of the study was to describe patients' experience of yoga as a treatment for hypertension, as well as their experience of living with hypertension. DESIGN: Qualitative interview study Method and materials: In 2013-2014, in southern Sweden, patients with hypertension from three health care centres were invited to participate in a randomised controlled trial on yoga for hypertension. After completion of the study, eight women and five men (aged 35-79), who had practiced the yoga intervention, were interviewed about their experiences. We used a semi-structured interview guide according to Kvale. Qualitative analysis was conducted by systematic text condensation inspired by Malterud. RESULTS: Two main themes emerged during the analysis process: Yoga - a laborious way to well-being and hypertension - a silent disease. The positive experiences of doing yoga were described in terms of tranquillity and increased agility. The drawbacks were mainly linked to the time required to perform the exercises. Living with high blood pressure and having to take medication can imply a stigma and cause concerns for future cardiovascular events. Most patients that we interviewed expressed a wish to find alternative ways to treat their high blood pressure. Participating in the yoga study was seen as a good possibility to try such an alternative way. CONCLUSIONS: Many patients with hypertension in Swedish primary care seem to be interested in trying alternative treatments to control blood pressure. The patients in our study experienced several benefits from doing yoga, but they also pointed out difficulties in implementing yoga as a regular and permanent lifestyle change.

Role of IL-8, CRP and epidermal growth factor in depression and anxiety patients treated with mindfulness-based therapy or cognitive behavioral therapy in primary health care.

Epidermal growth factor (EGF) and inflammatory markers have been associated with various neuro-psychiatric disorders. However, their role in mild to moderate depression and anxiety patients treated with mindfulness-based group therapy (mindfulness) or cognitive behavioral therapy (CBT) is not known. In this study we analyzed plasma levels of interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hsCRP) and EGF before (baseline) and after treatment (8 weeks) and investigated their role in response to both arms of the treatment. To cover variety of mental symptoms, treatment response was analyzed by four scales, the Montgomery-Åsberg depression rating scale (MADRS), Hospital anxiety and depression scale- Depression (HADS-D) and anxiety (HADS-A) and patients health questionnaire-9. EGF levels were significantly decreased after both mindfulness and CBT and were associated with treatment response on all scales independent of the use of tranquilizers and antidepressant treatment. Moreover, baseline EGF levels were significantly associated only with baseline scores of anxiety scale. Levels of inflammatory markers analyzed in this study, were not significantly associated with treatment response on any scale. Our findings suggest that improvement in symptoms of depression and anxiety after both mindfulness and CBT is associated with changes in EGF levels but not with the inflammatory markers.

Kinesiophobia and its relation to pain characteristics and cognitive affective variables in older adults with chronic pain.

BACKGROUND: The contribution of kinesiophobia (fear of movement) to the pain experience among older adults has been poorly evaluated. The aim of this study was to study prevalence at baseline, development over a 12-month period and cognitive-affective variables of kinesiophobia in a population-based sample of older adults with chronic pain. METHODS: The study included 433 older adults (+65 years) with chronic pain (mean age 74.8 years) randomly selected using a Swedish register of inhabitants. Kinesiophobia was measured at baseline and 12-month follow-up with the 11-item version of the Tampa Scale of Kinesiophobia (TSK-11). Associations of demographic-, cognitive affective - and pain-related variables to kinesiophobia were analysed with linear regression analyses. RESULTS: The mean level of kinesiophobia was low. Worsening and recovering from kinesiophobia occurred over time, but the mean level of kinesiophobia remained unchanged (p = 0.972). High levels of kinesiophobia (TSK ≥35) were found among frailer and older adults predominately living in care homes, but not dependent on sex. Poor self-perceived health (OR = 8.84) and high pain intensity (OR = 1.22) were significantly associated with kinesiophobia. CONCLUSION: Results indicate that potential interventions regarding kinesiophobia among older adults should aim to decrease pain intensity and strengthen health beliefs.

Yoga's effect on inflammatory biomarkers and metabolic risk factors in a high risk population - a controlled trial in primary care.

BACKGROUND: Yoga can reduce blood pressure and has also been suggested to reduce inflammatory biomarkers and metabolic risk factors for cardiovascular diseases (CVDs). We aimed to assess the benefit of two yoga interventions on inflammatory biomarkers and metabolic risk factors in a high risk population in primary care. METHODS: Adult patients from a health care center in Sweden, with diagnosed hypertension, were invited to undergo a baseline check at the health care center. Baseline check included standardized blood pressure measurement, BMI and weight circumference measurements, blood sampling (hs-CRP, IL-6, FP-glucose, HbA1c, cholesterol, TG, LDL and HDL) and a questionnaire on self-rated quality of life (WHOQOL-BREF). There were three groups: 1) yoga class with yoga instructor; 2) yoga at home; and 3) a control group. In total, 83 patients were included and matched at the group level for systolic blood pressure. A majority of the patients (92 %) were on antihypertensive medication, which they were requested not to change during the study. After 12 weeks of intervention, the assessments were performed again. RESULTS: We recorded no evidence that yoga altered inflammatory biomarkers or metabolic risk factors in our study population. A total of 49 participants (59 %) met the criteria for metabolic syndrome. CONCLUSION: The yoga interventions performed in our study did not affect inflammatory biomarkers or metabolic risk factors associated with CVD in the study population of primary care patients with hypertension. Further randomized trials are needed to elucidate the effects of yoga on CVD risk factors in this particular group. TRAIL REGISTRATION: NCT01302535 , February 22, 2011.

An extended Swedish national adoption study of alcohol use disorder.

IMPORTANCE: Alcohol use disorder (AUD) runs strongly in families. It is unclear to what extent the cross-generational transmission of AUD results from genetic vs environmental factors. OBJECTIVE: To determine to what extent genetic and environmental factors contribute to the risk for AUD. DESIGN, SETTING, AND PARTICIPANTS: Follow-up in 8 public data registers of adoptees, their biological and adoptive relatives, and offspring and parents from stepfamilies and not-lived-with families in Sweden. In this cohort study, subtypes of AUD were assessed by latent class analysis. A total of 18,115 adoptees (born 1950-1993) and 171,989 and 107,696 offspring of not-lived-with parents and stepparents, respectively (born 1960-1993). MAIN OUTCOMES AND MEASURES: Alcohol use disorder recorded in medical, legal, or pharmacy registry records. RESULTS: Alcohol use disorder in adoptees was significantly predicted by AUD in biological parents (odds ratio, 1.46; 95% CI, 1.29-1.66) and siblings (odds ratio, 1.94; 95% CI, 1.55-2.44) as well as adoptive parents (odds ratio, 1.40; 95% CI, 1.09-1.80). Genetic and environmental risk indices created from biological and adoptive relatives acted additively on adoptee AUD liability. Results from biological and adoptive relatives were replicated and extended from examinations of, respectively, not-lived-with parents and stepparents. Multivariate models in these families showed that AUD in offspring was significantly predicted by AUD, drug abuse, psychiatric illness, and crime in not-lived-with parents and by AUD, drug abuse, crime, and premature death in stepparents. Latent class analyses of adoptees and offspring of not-lived-with parents with AUDs revealed 3 AUD classes characterized by (1) female preponderance and high rates of psychiatric illness, (2) mild nonrecurrent symptoms, and (3) early-onset recurrence, drug abuse, and crime. These classes had distinct genetic signatures in the patterns of risk for various disorders in their not-lived-with parents and striking differences in the rates of recorded mood disorders. CONCLUSIONS AND RELEVANCE: Parent-offspring transmission of AUD results from both genetic and environmental factors. Genetic risk for AUD reflects both a specific liability to AUD and to other externalizing disorders. Environmental risk reflects features of both parental psychopathology and other aspects of the rearing environment. Alcohol use disorder is a heterogeneous syndrome and meaningful subtypes emerged from latent class analysis, which were validated by patterns of disorders in biological parents and specific psychiatric comorbidities. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.

Mindfulness group therapy in primary care patients with depression, anxiety and stress and adjustment disorders: randomised controlled trial.

BACKGROUND: Individual-based cognitive-behavioural therapy (CBT) is in short supply and expensive. AIMS: The aim of this randomised controlled trial (RCT) was to compare mindfulness-based group therapy with treatment as usual (primarily individual-based CBT) in primary care patients with depressive, anxiety or stress and adjustment disorders. METHOD: This 8-week RCT (ClinicalTrials.gov ID: NCT01476371) was conducted during spring 2012 at 16 general practices in Southern Sweden. Eligible patients (aged 20-64 years) scored ≥10 on the Patient Health Questionnaire-9, ≥7 on the Hospital Anxiety and Depression Scale or 13-34 on the Montgomery-Åsberg Depression Rating Scale (self-rated version). The power calculations were based on non-inferiority. In total, 215 patients were randomised. Ordinal mixed models were used for the analysis. RESULTS: For all scales and in both groups, the scores decreased significantly. There were no significant differences between the mindfulness and control groups. CONCLUSIONS: Mindfulness-based group therapy was non-inferior to treatment as usual for patients with depressive, anxiety or stress and adjustment disorders.

Impact of yoga on blood pressure and quality of life in patients with hypertension - a controlled trial in primary care, matched for systolic blood pressure.

BACKGROUND: Medical treatment of hypertension is not always sufficient to achieve blood pressure control. Despite this, previous studies on supplementary therapies, such as yoga, are relatively few. We investigated the effects of two yoga interventions on blood pressure and quality of life in patients in primary health care diagnosed with hypertension. METHODS: Adult patients (age 20-80 years) with diagnosed hypertension were identified by an electronic chart search at a primary health care center in southern Sweden. In total, 83 subjects with blood pressure values of 120-179/≤109 mmHg at baseline were enrolled. At baseline, the patients underwent standardized blood pressure measurement at the health care center and they completed a questionnaire on self-rated quality of life (WHOQOL-BREF). There were three groups: 1) yoga class with yoga instructor (n = 28); 2) yoga at home (n = 28); and 3) a control group (n = 27). The participants were matched at the group level for systolic blood pressure. After 12 weeks of intervention, the assessments were performed again. At baseline a majority of the patients (92%) were on antihypertensive medication, and the patients were requested not to change their medication during the study. RESULTS: The yoga class group showed no improvement in blood pressure or self-rated quality of life, while in the yoga at home group there was a decline in diastolic blood pressure of 4.4 mmHg (p < 0.05) compared to the control group. Moreover, the yoga at home group showed significant improvement in self-rated quality of life compared to the control group (p < 0.05). CONCLUSIONS: A short yoga program for the patient to practice at home seems to have an antihypertensive effect, as well as a positive effect on self-rated quality of life compared to controls. This implies that simple yoga exercises may be useful as a supplementary blood pressure therapy in addition to medical treatment when prescribed by primary care physicians.