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

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

Wait Up!: Attachment and Sovereign Power.

Sociologists and feminist scholars have, over many decades, characterised attachment as a social construction that functions to support political and gender conservatism. We accept that attachment theory has seen use to these ends and consider recent deployments of attachment theory as justification for a minimal State within conservative political discourse in the UK since 2009. However, we contest that attachment is reducible to its discursive construction. We consider Judith Butler's depiction of the infant attached to an abusive caregiver as a foundation and parallel to the position of the adult citizen subjected to punitive cultural norms and political institutions. We develop and qualify Butler's account, drawing on the insights offered by the work of Lauren Berlant. We also return to Foucault's Psychiatric Power lectures, in which familial relations are situated as an island of sovereign power within the sea of modern disciplinary institutions. These reflections help advance analysis of three important issues: the social and political implications of attachment research; the relationship between disciplinary and sovereign power in the affective dynamic of subjection; and the political and ethical status of professional activity within the psy disciplines.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10767-014-9192-

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

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

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

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

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

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