Association between dopaminergic polymorphisms and borderline personality traits among at-risk young adults and psychiatric inpatients

Background: In the development of borderline personality disorder (BPD) both genetic and environmental factors have important roles. The characteristic affective disturbance and impulsive aggression are linked to imbalances in the central serotonin system, and most of the genetic association studies focused on serotonergic candidate genes. However, the efficacy of dopamine D2 receptor (DRD2) blocking antipsychotic drugs in BPD treatment also suggests involvement of the dopamine system in the neurobiology of BPD.Methods: In the present study we tested the dopamine dysfunction hypothesis of impulsive self- and other-damaging behaviors: borderline and antisocial traits were assessed by Structured Clinical Interview for Diagnosis (SCID) for DSM-IV in a community-based US sample of 99 young adults from low-to-moderate income families. For the BPD trait analyses a second, independent group was used consisting of 136 Hungarian patients with bipolar or major depressive disorder filling out self-report SCID-II Screen questionnaire. In the genetic association analyses the previously indicated polymorphisms of the catechol-O-methyl-transferase (COMT Val158Met) and dopamine transporter (DAT1 40 bp VNTR) were studied. In addition, candidate polymorphisms of the DRD2 and DRD4 dopamine receptor genes were selected from the impulsive behavior literature.Results: The DRD2 TaqI B1-allele and A1-allele were associated with borderline traits in the young adult sample (p = 0.001, and p = 0.005, respectively). Also, the DRD4 -616 CC genotype appeared as a risk factor (p = 0.02). With severity of abuse accounted for in the model, genetic effects of the DRD2 and DRD4 polymorphisms were still significant (DRD2 TaqIB: p = 0.001, DRD2 TaqIA: p = 0.008, DRD4 -616 C/G: p = 0.002). Only the DRD4 promoter finding was replicated in the independent sample of psychiatric inpatients (p = 0.007). No association was found with the COMT and DAT1 polymorphisms.Conclusions: Our results of the two independent samples suggest a possible involvement of the DRD4 -616 C/G promoter variant in the development of BPD traits. In addition, an association of the DRD2 genetic polymorphisms with impulsive self-damaging behaviors was also demonstrated. © 2010 Nemoda et al; licensee BioMed Central Ltd

Attachment and temperament revisited: infant distress, attachment disorganisation and the serotonin transporter polymorphism

Objective: This study’s aim was to evaluate whether infant disorganised attachment and infant proneness to distress exhibited differential relations to infant genetic factors as indexed by the serotonin transporter polymorphism. Background: The role of the short allele of the serotonin transporter polymorphism (5-HTTLPR) in enhancing sensitivity to fearful and negative affect has been well-established. In the current study, we used this known property of the short allele to provide a test of an important postulate of attachment theory, namely that infant attachment security or disorganisation is not a function of the infant’s proneness to distress. Methods: Participants were 39 parents and infants assessed between 12 and 18 months in the Strange Situation Procedure. Genotype categories for the 5-HTTLPR (and rs25531) were created by both the original and the reclassified grouping system; infant proneness to distress was assessed directly in the Strange Situation Procedure. We also assessed maternal behaviour at 18 months to evaluate whether any observed genetic effect indicated a passive effect through the mother. Results: Consistent with previous findings, the 5-HTTLPR short allele was significantly related to the infant’s wariness and distress, but was not related to attachment security or attachment disorganisation. In addition, maternal disrupted interaction with the infant was not related to infant genotype or infant distress. Conclusion: Results support the concept that infant proneness to distress is associated with serotonergic factors while infant attachment security or disorganisation is not a function of either 5-HTTLPR or behaviourally rated proneness to distress. © 2015 Society for Reproductive and Infant Psychology

Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory conditions. By immunohistochemistry of renal biopsies, patients with focal or crescentic glomerular lesions were found to have the highest expression of calprotectin and those with sclerotic the least. Serum levels of calprotectin as measured by ELISA were elevated in patients with active AAV and the levels decreased but did not normalize during remission, suggesting subclinical inflammation. Calprotectin levels in patients with limited systemic disease increased following treatment withdrawal and were significantly elevated in patients who relapsed compared with those who did not. As assessed by flow cytometry, patients with AAV had higher monocyte and neutrophil cell surface calprotectin expression than healthy controls, but this was not associated with augmented mRNA expression in CD14(+) monocytes or CD16(+) neutrophils. Thus, serum calprotectin is a potential disease biomarker in patients with AAV, and may have a role in disease pathogenesis

Exploring disorganized attachment style among Malay mothers in Malaysia: a study using the Attachment Style Interview

This article explores emerging themes involving disorganized attachment style among Malay Muslim mothers using the Attachment Style Interview (ASI). Analysis of the 18 mothers with disorganized attachment style (those with combined anxious and avoidant styles) utilized themes deemed important from the attachment research literature and selected based on a careful reading of the narrative cases. These include more extreme negative interpersonal experiences than found in other insecure attachment style descriptors, and included partner violence and related isolation/social exclusion. It also indicated more complex cognitive-affective disturbance including mixed or contradictory dependency patterns and both angry and fearful attitudes to others. We discuss the concept of disorganized attachment style in relation to abuse, social exclusion, and its implication for psychopathology, intervention, and treatment

Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men

BACKGROUND : Prostate cancer incidence and mortality rates are significantly increased in African–American men, but limited studies have been performed within Sub–Saharan African populations. As mitochondria control energy metabolism and apoptosis we speculate that somatic mutations within mitochondrial genomes are candidate drivers of aggressive prostate carcinogenesis. METHODS : We used matched blood and prostate tissue samples from 87 South African men (77 with African ancestry) to perform deep sequencing of complete mitochondrial genomes. Clinical presentation was biased toward aggressive disease (Gleason score >7, 64%), and compared with men without prostate cancer either with or without benign prostatic hyperplasia. RESULTS : We identified 144 somatic mtDNA single nucleotide variants (SNVs), of which 80 were observed in 39 men presenting with aggressive disease. Both the number and frequency of somatic mtDNA SNVs were associated with higher pathological stage. CONCLUSIONS : Besides doubling the total number of somatic PCa-associated mitochondrial genome mutations identified to date, we associate mutational load with aggressive prostate cancer status in men of African ancestry.NIH R21- CA170081, Australian Prostate Cancer Research Centre NSW, the J. Craig Venter Institute, the Garvan Institute, the Petre Foundation, Australia, the Cancer Association of South Africa (CANSA).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0045hb201

Links between maternal postpartum depressive symptoms, maternal distress, infant gender and sensitivity in a high-risk population

<p>Abstract</p> <p>Background</p> <p>Maternal postpartum depression has an impact on mother-infant interaction. Mothers with depression display less positive affect and sensitivity in interaction with their infants compared to non-depressed mothers. Depressed women also show more signs of distress and difficulties adjusting to their role as mothers than non-depressed women. In addition, depressive mothers are reported to be affectively more negative with their sons than with daughters.</p> <p>Methods</p> <p>A non-clinical sample of 106 mother-infant dyads at psychosocial risk (poverty, alcohol or drug abuse, lack of social support, teenage mothers and maternal psychic disorder) was investigated with EPDS (maternal postpartum depressive symptoms), the CARE-Index (maternal sensitivity in a dyadic context) and PSI-SF (maternal distress). The baseline data were collected when the babies had reached 19 weeks of age.</p> <p>Results</p> <p>A hierarchical regression analysis yielded a highly significant relation between the PSI-SF subscale "parental distress" and the EPDS total score, accounting for 55% of the variance in the EPDS. The other variables did not significantly predict the severity of depressive symptoms. A two-way ANOVA with "infant gender" and "maternal postpartum depressive symptoms" showed no interaction effect on maternal sensitivity.</p> <p>Conclusions</p> <p>Depressive symptoms and maternal sensitivity were not linked. It is likely that we could not find any relation between both variables due to different measuring methods (self-reporting and observation). Maternal distress was strongly related to maternal depressive symptoms, probably due to the generally increased burden in the sample, and contributed to 55% of the variance of postpartum depressive symptoms.</p

Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study.

OBJECTIVE: To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults. DESIGN: Population based cohort study. SETTING AND PARTICIPANTS: QResearch database, comprising 1205 general practices in England with linkage to covid-19 test results, Hospital Episode Statistics, and death registry data. 6.08 million adults aged 19-100 years were included in the derivation dataset and 2.17 million in the validation dataset. The derivation and first validation cohort period was 24 January 2020 to 30 April 2020. The second temporal validation cohort covered the period 1 May 2020 to 30 June 2020. MAIN OUTCOME MEASURES: The primary outcome was time to death from covid-19, defined as death due to confirmed or suspected covid-19 as per the death certification or death occurring in a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the period 24 January to 30 April 2020. The secondary outcome was time to hospital admission with confirmed SARS-CoV-2 infection. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance, including measures of discrimination and calibration, was evaluated in each validation time period. RESULTS: 4384 deaths from covid-19 occurred in the derivation cohort during follow-up and 1722 in the first validation cohort period and 621 in the second validation cohort period. The final risk algorithms included age, ethnicity, deprivation, body mass index, and a range of comorbidities. The algorithm had good calibration in the first validation cohort. For deaths from covid-19 in men, it explained 73.1% (95% confidence interval 71.9% to 74.3%) of the variation in time to death (R2); the D statistic was 3.37 (95% confidence interval 3.27 to 3.47), and Harrell's C was 0.928 (0.919 to 0.938). Similar results were obtained for women, for both outcomes, and in both time periods. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths within 97 days was 75.7%. People in the top 20% of predicted risk of death accounted for 94% of all deaths from covid-19. CONCLUSION: The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19. The absolute risks presented, however, will change over time in line with the prevailing SARS-C0V-2 infection rate and the extent of social distancing measures in place, so they should be interpreted with caution. The model can be recalibrated for different time periods, however, and has the potential to be dynamically updated as the pandemic evolves

Development of atypical parental behavior during an inpatient family preservation intervention program

Since failed reunification is a detrimental outcome for children, particularly infants and toddlers, the aim of this study was to gain insight into support to families in multiple-problem situations to help them achieve sustainable good-enough parenting. Therefore, we examined outcomes of an assessment-based inpatient family preservation program. We prepared a thorough target-population description (n = 70) using file analysis. Next, we examined atypical parental behavior during the intervention using the Atypical Maternal Behavior Instrument for Assessment and Classification with a repeated measures design (n = 30). The family files revealed a great number of issues at the family, parent, and child levels, such as practical matters, problems in parent functioning and between parents, and difficulties in the broader environment. We found a significant decline in three dimensions of atypical parental behavior over time. This program has great potential in supporting vulnerable families in their pursuit of family preservation

Environmental and genetic influences on early attachment

Attachment theory predicts and subsequent empirical research has amply demonstrated that individual variations in patterns of early attachment behaviour are primarily influenced by differences in sensitive responsiveness of caregivers. However, meta-analyses have shown that parenting behaviour accounts for about one third of the variance in attachment security or disorganisation. The exclusively environmental explanation has been challenged by results demonstrating some, albeit inconclusive, evidence of the effect of infant temperament. In this paper, after reviewing briefly the well-demonstrated familial and wider environmental influences, the evidence is reviewed for genetic and gene-environment interaction effects on developing early attachment relationships. Studies investigating the interaction of genes of monoamine neurotransmission with parenting environment in the course of early relationship development suggest that children's differential susceptibility to the rearing environment depends partly on genetic differences. In addition to the overview of environmental and genetic contributions to infant attachment, and especially to disorganised attachment relevant to mental health issues, the few existing studies of gene-attachment interaction effects on development of childhood behavioural problems are also reviewed. A short account of the most important methodological problems to be overcome in molecular genetic studies of psychological and psychiatric phenotypes is also given. Finally, animal research focusing on brain-structural aspects related to early care and the new, conceptually important direction of studying environmental programming of early development through epigenetic modification of gene functioning is examined in brief

Childhood deaths from external causes in Estonia, 2001–2005

<p>Abstract</p> <p>Background</p> <p>In 2000, the overall rate of injury deaths in children aged 0–14 was 28.7 per 100000 in Estonia, which is more than 5 times higher than the corresponding rate in neighbouring Finland. This paper describes childhood injury mortality in Estonia by cause and age groups, and validates registration of these deaths in the Statistical Office of Estonia against the autopsy data.</p> <p>Methods</p> <p>The data on causes of all child deaths in Estonia in 2001–2005 were abstracted from the autopsy protocols at the Estonian Bureau of Forensic Medicine. Average annual mortality rates per 100,000 were calculated. Coverage (proportion of the reported injury deaths from the total number of injury deaths) and accuracy (proportion of correctly classified injury deaths) of the registration of causes of death in Statistical Office of Estonia were assessed by comparing the Statistical Office of Estonia data with the data from Estonian Bureau of Forensic Medicine.</p> <p>Results</p> <p>Average annual mortality from external causes in 0–14 years-old children in Estonia was 19.1 per 100,000. Asphyxia and transport accidents were the major killers followed by poisoning and suicides. Relative contribution of these causes varied greatly between age groups. Intent of death was unknown for more than 10% of injury deaths. Coverage and accuracy of registration of injury deaths by Statistical Office of Estonia were 91.5% and 95.3%, respectively.</p> <p>Conclusion</p> <p>Childhood mortality from injuries in Estonia is among the highest in the EU. The number of injury deaths in Statistical Office of Estonia is slightly underestimated mostly due to misclassification for deaths from diseases. Accuracy of the Statistical Office of Estonia data was high with some underestimation of intentional deaths. Moreover, high proportion of death with unknown intent suggests underestimation of intentional deaths.</p> <p>Reduction of injury deaths should be given a high priority in Estonia. More information on circumstances around death is needed to enable establishing the intent of death.</p