Karolina Palmér

Genetic and Familial Environmental Influences on the Risk for Drug Abuse: A National Swedish Adoption Study

CONTEXT Prior research suggests that drug abuse (DA) is strongly influenced by both genetic and familial environmental factors. No large-scale adoption study has previously attempted to verify and integrate these findings. OBJECTIVE To determine how genetic and environmental factors contribute to the risk for DA. DESIGN Follow-up in 9 public databases (1961-2009) of adopted children and their biological and adoptive relatives. SETTING Sweden. PARTICIPANTS The study included 18 115 adopted children born between 1950 and 1993; 78,079 biological parents and siblings; and 51,208 adoptive parents and siblings. MAIN OUTCOME MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS Risk for DA was significantly elevated in the adopted offspring of biological parents with DA (odds ratio, 2.09; 95% CI, 1.66-2.62), in biological full and half siblings of adopted children with DA (odds ratio, 1.84; 95% CI, 1.28-2.64; and odds ratio, 1.41; 95% CI, 1.19-1.67, respectively), and in adoptive siblings of adopted children with DA (odds ratio, 1.95; 95% CI, 1.43-2.65). A genetic risk index (including biological parental or sibling history of DA, criminal activity, and psychiatric or alcohol problems) and an environmental risk index (including adoptive parental history of divorce, death, criminal activity, and alcohol problems, as well as an adoptive sibling history of DA and psychiatric or alcohol problems) both strongly predicted the risk for DA. Including both indices along with sex and age at adoption in a predictive model revealed a significant positive interaction between the genetic and environmental risk indices. CONCLUSIONS Drug abuse is an etiologically complex syndrome strongly influenced by a diverse set of genetic risk factors reflecting a specific liability to DA, by a vulnerability to other externalizing disorders, and by a range of environmental factors reflecting marital instability, as well as psychopathology and criminal behavior in the adoptive home. Adverse environmental effects on DA are more pathogenic in individuals with high levels of genetic risk. These results should be interpreted in the context of limitations of the diagnosis of DA from registries.

Determination of 14 Circulating microRNAs in Swedes and Iraqis with and without Diabetes Mellitus Type 2

Background Recent reports suggest that immigrants from Middle Eastern countries are a high-risk group for type 2 diabetes (T2D) compared with Swedes, and that the pathogenesis of T2D may be ethnicity-specific. Deregulation of microRNA (miRNA) expression has been demonstrated to be associated with T2D but ethnic differences in miRNA have not been investigated. The aim of this study was to explore the ethnic specific expression (Swedish and Iraqi) of a panel of 14 previously identified miRNAs in patients without T2D (including those with prediabetes) and T2D. Methods A total of 152 individuals were included in the study (84 Iraqis and 68 Swedes). Nineteen Iraqis and 14 Swedes were diagnosed with T2D. Expression of the 14 selected miRNAs (miR-15a, miR-20, miR-21, miR-24, miR-29b, miR-126, miR-144, miR-150, miR-197, miR-223, miR-191, miR-320a, miR-486-5p, and miR-28-3p) in plasma samples was measured by real-time PCR. Results In the whole study population, the expression of miR-24 and miR-29b was significantly different between T2D patients and controls after adjustment for age, sex, waist circumference, family history of T2D, and a sedentary lifestyle. Interestingly, when stratifying the study population according to country of birth, we found that higher expression of miR-144 was significantly associated with T2D in Swedes (OR = 2.43, p = 0.035), but not in Iraqis (OR = 0.54, p = 0.169). The interaction test was significant (p = 0.017). Conclusion This study suggests that the association between plasma miR-144 expression and T2D differs between Swedes and Iraqis.

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.

Diagnostic potential of plasma microRNA signatures in patients with deep-vein thrombosis

For excluding deep-vein thrombosis (DVT), a negative D-dimer and low clinical probability are used to rule out DVT. Circulating microRNAs (miRNAs) are stably present in the plasma, serum and other body fluids. Their diagnostic function has been investigated in many diseases but not in DVT. The aims of present study were to assess the diagnostic ability of plasma miRNAs in DVT and to examine their correlation with known markers of hypercoagulability, such as D-dimer and APC-PCI complex. Plasma samples were obtained from 238 patients (aged 16-95 years) with suspected DVT included in a prospective multicentre management study (SCORE). We first performed miRNA screening of plasma samples from three plasma pools containing plasma from 12 patients with DVT and three plasma pools containing plasma from 12 patients without DVT using a microRNA Ready-to-use PCR Panel comprising 742 miRNA primer sets. Thirteen miRNAs that differentially expressed were further investigated by quantitative real-time (qRT)-PCR in the entire cohort. The plasma level of miR-424-5p (p=0.01) were significantly higher, whereas the levels of miR-136-5p (p=0.03) were significantly lower in DVT patients compared to patients without DVT. Receiver-operating characteristic curve analysis showed the area under the curve (AUC) values of 0.63 for miR-424-5p and 0.60 for miR-136-5p. The plasma level of miR-424-5p was associated with both D-dimer and APC-PCI complex levels (p<0.0001 and p=0.001, respectively). In conclusions, these findings indicate that certain miRNAs are associated with DVT and markers of hypercoagulability, though their diagnostic abilities are probably too low.

Is acculturation associated with physical activity among female immigrants in Sweden

BACKGROUND Immigrant women in Sweden have lower levels of leisure time physical activity (LTPA) than Swedish-born women. The reasons are unclear, although acculturation has been suggested to play a role. METHODS We used a cross-sectional study design to investigate the association between LTPA and two indicators of acculturation: (i) language proficiency (ability to understand news reports on the radio and television) and (ii) age at the time of migration, and if there existed a modifying effect on these hypothesized associations. The study sample consisted of 1651 women, aged 18-65, living in Sweden and born in Finland, Chile or Iraq. A postal questionnaire (translated into the womens native language) was used to collect the variables. The International Physical Activity Questionnaire was used to assess LTPA. Data were collected in 2002-05 and analyzed in 2009-10. A partial-proportional odds model was used for the analysis. RESULTS Increased language proficiency was associated with increased LTPA [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.57-3.41]. Country of birth modified the association. Furthermore, younger age at migration was associated with increased LTPA (OR = 1.44, 95% CI = 1.01-2.03). CONCLUSIONS Increased language proficiency has the potential to be an important health-promoting factor among immigrant women.

The association between cytokines and insulin sensitivity in Iraqi immigrants and native Swedes

Objectives To investigate the associations between cytokines and insulin sensitivity in Swedish residents born in Iraq and Swedish residents born in Sweden. Design Cross-sectional study. Settings Iraqi and Swedish origin residents of Rosengård area of Malmö, aged 45–65 years, were randomly selected from the census register. Participants/methods 194 (Iraqi, n=107; Swedish, n=87) participants agreed to participate in the study. Nineteen participants dropped out (Iraqi, n=11; Swedish, n=8). Participants who had already been diagnosed with type 2 diabetes mellitus (T2DM), those who could not participate in an oral glucose tolerance test and those who had a cold/fever at the time of blood sampling were excluded. In total, serum samples from 135 individuals of Swedish (n=62) and Iraqi (n=73) origin were included. Serum concentrations of a panel of 10 cytokines, comprising interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p70), IL-13, interferon-γ and tumour necrosis factor-α were analysed by Luminex multiplex assay. Results In the whole study population, levels of all tested cytokines were inversely associated with insulin sensitivity index (ISI), independent of age, sex, body mass index (BMI), sedentary lifestyle and family history of T2DM (p ≤ 0.05). Interestingly, stratification of the study population according to country of birth showed a significant inverse association between all tested cytokines and ISI in the Iraqi-born population (p ≤ 0.01). The association was independent of age, sex, BMI, sedentary lifestyle and family history of T2DM. In contrast, with the exception for IL-6 (p=0.05), no other tested cytokine was found to be significantly associated with ISI in the Swedish-born population (p≥0.05). Conclusions Our results show an association between cytokines and ISI in the Iraqi-born population but not in the Swedish-born population.

Association of mitochondrial DNA in peripheral blood with depression, anxiety and stress- and adjustment disorders in primary health care patients

Mitochondrial dysfunction may result in a variety of diseases. The objectives here were to examine possible differences in mtDNA copy number between healthy controls and patients with depression, anxiety or stress- and adjustment disorders; the association between mtDNA copy number and disease severity at baseline; and the association between mtDNA copy number and response after an 8-week treatment (mindfulness, cognitive based therapy). A total of 179 patients in primary health care (age 20-64 years) with depression, anxiety and stress- and adjustment disorders, and 320 healthy controls (aged 19-70 years) were included in the study. Relative mtDNA copy number was measured using quantitative real-time PCR on peripheral blood samples. We found that the mean mtDNA copy number was significantly higher in patients compared to controls (84.9 vs 75.9, p<0.0001) at baseline. The difference in mtDNA copy number between patients and controls remained significant after controlling for age and sex (ß=8.13, p<0.0001; linear regression analysis). The mtDNA copy number was significantly associated with Patient Health Questionnaire (PHQ-9) scores (β=0.57, p=0.02) at baseline. After treatment, the change in mtDNA copy number was significantly associated with the treatment response, i.e., change in Hospital Anxiety and Depression Scale (HADS-D) and PHQ-9 scores (ß=1.00, p=0.03 and ß=0.65, p=0.04, respectively), after controlling for baseline scores, age, sex, BMI, smoking status, alcohol drinking and medication. Our findings show that mtDNA copy number is associated with symptoms of depression, anxiety and stress- and adjustment disorders and treatment response in these disorders.

Circulating human epidermal growth factor receptor 2 (HER2) is associated with hyperglycaemia and insulin resistance.

Type 2 diabetes mellitus (T2DM) and HER2 are associated with cancer although the role of HER2 in T2DM is not well defined. Our aim was to investigate the association between HER2 levels and T2DM and whether that association was different in Swedish people born in Iraq or Sweden.Type 2 diabetes mellitus (T2DM) and human epidermal growth factor receptor 2 (HER2) are associated with cancer, although the role of HER2 in T2DM is not well defined. The aim of this study was to investigate the association between HER2 levels and T2DM and whether that association differed in Swedish people born in Iraq or Sweden.

The association between apolipoprotein M and insulin resistance varies with country of birth

BACKGROUND AND AIMS Risk of type 2 diabetes mellitus (T2DM) differs according to ethnicity. Levels of apolipoprotein M (ApoM) have been shown to be decreased in T2DM. However, its role in different ethnicities is not known. We examined the differences in plasma ApoM levels in Swedish residents born in Iraq (Iraqis) and Sweden (Swedes) in relation to T2DM and insulin resistance (IR). METHODS AND RESULTS Iraqis and Swedes, aged 45-65 years residing in Rosengård area of Malmö were randomly selected from census records and underwent an oral glucose tolerance test. Plasma levels of ApoM were quantified in 162 participants (Iraqis, n = 91; Swedes, n = 71) by a sandwich ELISA method. Age-, sex-, and body mass index (BMI) adjusted plasma ApoM levels differed by country of birth, with Swedes having 18% higher levels compared to Iraqis (p = 0.001). ApoM levels (mean ± SD) were significantly decreased in Swedes with T2DM (0.73 ± 0.18) compared to those with normal glucose tolerance (NGT) (0.89 ± 0.24; p = 0.03). By contrast, no significant difference in ApoM levels was found between Iraqis with T2DM (0.70 ± 0.17) and those with NGT (0.73 ± 0.13; p = 0.41). In multivariate linear regression analysis with an interaction term between IR and country of birth, low ApoM levels remained significantly associated with IR in Swedes (p = 0.008), independently of age, sex, BMI, family history of diabetes, HDL, LDL, and triglycerides, but not in Iraqis (p = 0.35). CONCLUSION Our results show that ApoM levels differ according to country of birth and are associated with IR and T2DM only in Swedes.

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

Abstract 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 (β=−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) (β=−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.