Kristin Caspers

Methylation Matters: Interaction Between Methylation Density and Serotonin Transporter Genotype Predicts Unresolved Loss or Trauma

BACKGROUND Do genetic or epigenetic factors play a role in making some individuals more vulnerable than others to loss of attachment figures or other traumatic experiences? METHODS DNA was obtained from growth phase entrained Epstein-Barr Virus (EBV) transformed lymphoblast cell lines from 143 adopted participants. Genotype of the serotonin transporter linked polymorphic region (5HTTLPR) was determined, and methylation ratios for each of the C-phosphate-G (CpG) residues were assessed using quantitative mass spectroscopy. Unresolved loss or trauma was established using the Berkeley Adult Attachment Interview. RESULTS Higher levels of methylation of the 5HTT promoter associated CpG island were associated with increased risk of unresolved responses to loss or other trauma in carriers of the usually protective 5HTTLPR//variant. The ss variant of 5HTTLPR predicted more unresolved loss or trauma, but only in case of lower levels of methylation. Higher levels of methylation of the ss variant were associated with less unresolved loss or other trauma. CONCLUSIONS Associations between 5HTTLPR polymorphisms and psychological problems are significantly altered by environmentally induced methylation patterns. Methylation may serve as the interface between adverse environment and the developing organism.

Attachment as an organizer of behavior: implications for substance abuse problems and willingness to seek treatment

BackgroundAttachment theory allows specific predictions about the role of attachment representations in organizing behavior. Insecure attachment is hypothesized to predict maladaptive emotional regulation whereas secure attachment is hypothesized to predict adaptive emotional regulation. In this paper, we test specific hypotheses about the role of attachment representations in substance abuse/dependence and treatment participation. Based on theory, we expect divergence between levels of maladaptive functioning and adaptive methods of regulating negative emotions.MethodsParticipants for this study consist of a sample of adoptees participating in an ongoing longitudinal adoption study (n = 208). The Semi-Structured Assessment of the Genetics of Alcohol-II [41] was used to determine lifetime substance abuse/dependence and treatment participation. Attachment representations were derived by the Adult Attachment Interview [AAI; [16]]. We constructed a prior contrasts reflecting theoretical predictions for the association between attachment representations, substance abuse/dependence and treatment participation.ResultsLogistic regression was used to test our hypotheses. As predicted, individuals classified as dismissing, preoccupied or earned-secure reported the highest rates of substance abuse/dependence. Individuals classified as dismissing reported significantly lower rates of treatment participation despite their high rates of substance abuse/dependence. As expected, the continuous-secure group reported lowest rates of both substance abuse/dependence and treatment participation.ConclusionThe findings from this study identify attachment representations as an influential factor in understanding the divergence between problematic substance use and treatment utilization. The findings further imply that treatment may need to take attachment representations into account to promote successful recovery.

Genetic and environmental risk factors for the onset of drug use and problems in adoptees

Applying survival analysis methodology to age-of-onset data from an adoption study (N = 196), we present evidence that risks for both drug use and drug problems (DSM abuse or dependence) are elevated when combined antisocial personality (ASP) and substance abuse is present in the same biological parent. It is increased not only in comparison to adoptees with no known biological risk, but also when compared to adoptees with a biological background for only substance problems or only ASP. Neither of these later groups showed a statistically higher risk when compared with controls. Among adoptees with recurrent drug use, adolescent aggressivity is also elevated when the combined substance abuse/ASP biological diathesis is present. Statistical control for aggressivity diminished but did not eliminate the predictive significance of the combined biological diathesis for drug problems. We also verify, using more refined methodology, our previous reports of gender and adverse adoptive environmental influences on drug-related outcomes in these subjects. We could not document a biology-environment interaction, but power to do so was rather low. We argue that the observed biological associations are broadly consistent with generalization to other substances of an alcoholism phenotype similar to Cloningers Type II or Babors Type B.

Association between the serotonin transporter promoter polymorphism (5-HTTLPR) and adult unresolved attachment.

Research on antecedents of organized attachment has focused on the quality of caregiving received during childhood. In recent years, research has begun to examine the influence of genetic factors on quality of infant attachment. However, no published studies report on the association between specific genetic factors and adult attachment. This study examined the link between the 5-HTTLPR promoter polymorphism of the serotonin transporter gene and adult unresolved attachment assessed with the Adult Attachment Interview. Genetic material and information on attachment-related loss or trauma were available for 86 participants. Multivariate regression analyses showed an association between the short 5-HTTLPR allele and increased risk for unresolved attachment. Temperament traits and psychological symptoms did not affect the association between 5-HTTLPR and unresolved attachment. The authors hypothesize that the increased susceptibility to unresolved attachment among carriers of the short allele of 5-HTTLPR is consistent with the role of serotonin in modulation of frontal-amygdala circuitry. The findings challenge current thinking by demonstrating significant genetic influences on a phenomenon previously thought to be largely environmentally driven.

The association of the D2S2944 124 bp allele with recurrent early onset major depressive disorder in women

Major depressive disorder (MDD) and substance use disorders (SUD) are complex behavioral disorders with 40–50% heritability. Recently, Zubenko and colleagues reported that the 124 bp allele of D2S2944, a tetranucleotide repeat marker on 2q35, is strongly associated with recurrent, early onset MDD (RE‐MDD) and alcohol use disorders in women. To test this hypothesis, we examined the association of the 124 bp allele in a subset of 171 adoptees from the Iowa Adoption Studies, a population with high rates of MDD and SUD. We report that in our population, the 124 bp allele significantly associated with RE‐MDD in women. There was slight evidence of an increased of SUD in women with the 124 bp allele with the rate of cannabis use disorders reaching statistical significance (P < 0.04) before correction for multiple comparisons. Given the history of prior studies implicating 2q35 as a locus encoding vulnerability to co‐morbid alcoholism and depression, these findings strongly suggest that sequence variation conveying increased susceptibility to MDD and possibly SUD is in close proximity to D2S2944.

A sibling adoption study of adult attachment: The influence of shared environment on attachment states of mind

Abstract This study extends existing research investigating sibling concordance on attachment by examining concordance for adult attachment in a sample of 126 genetically unrelated sibling pairs. The Adult Attachment Interview (George, Kaplan, & Main, 1985; Main, Goldwyn, & Hesse, 2003) was used to assess states of mind with regard to attachment. The average age of the participants was 39 years old. The distribution of attachment classifications was independent of adoptive status. Attachment concordance rates were unassociated with gender concordance and sibling age difference. Concordance for autonomous/non-autonomous classifications was significant at 61% as was concordance for primary classifications at 53%. The concordance rate for not-unresolved/unresolved was non-significant at 67%. Our findings demonstrate similarity of working models of attachment between siblings independent of genetic relatedness between siblings and generations (i.e., parent and child). These findings extend previous research by further implicating shared environment as a major influence on sibling similarities on organized patterns of attachment in adulthood. The non-significant concordance for the unresolved classification suggests that unresolved loss or trauma may be less influenced by shared environment and more likely to be influenced by post-childhood experiences or genetic factors.

Epidemiology of Congenital Idiopathic Talipes Equinovarus in Iowa, 1997―2005

Congenital idiopathic talipes equinovarus (ITEV), also known as clubfoot, is a well‐recognized foot deformity. To date, prevalence estimates and descriptive data reported for ITEV have varied due to differences in study methodology. Using population‐based surveillance data collected by the Iowa Registry for Congenital and Inherited Disorders, we examined isolated ITEV births delivered from 1997 through 2005 and compared to live births in Iowa during the same time period. An overall prevalence was calculated for live, singleton full‐term births only. Prevalence odds ratios (POR)s and 95% confidence intervals (CI)s were examined for selected infant and parental characteristics. The prevalence of isolated ITEV was 11.4 per 10,000 live, singleton full‐term births (95% CI = 10.3, 12.6), with no significant variation in prevalence during the study period. Increased PORs were found for males (POR 1.8; 95% CI = 1.5, 2.3) and maternal smoking during pregnancy (POR = 1.5, 95% CI = 1.2, 1.9); low birth weight (<2,500 g) showed an increase among females (POR = 3.2, 95% CI = 1.5, 6.9) but not males (POR = 0.9, 95% CI = 0.3, 2.8). Elevated, but non‐significant, PORs were found for season of birth, maternal education, and trimester prenatal care was initiated; decreased PORs were found for fetal presentation, maternal race/ethnicity, parity, area of residence, and parental age at delivery. Our study of a well‐defined, homogenous sample suggested that prevalence of isolated ITEV in Iowa was similar to that reported in other population‐based studies and provided support for some, but not all, previously reported associations with infant and parental characteristics. More detailed, longitudinal studies of isolated ITEV are recommended.

IQ estimate smackdown: Comparing IQ proxy measures to the WAIS-III

Brief assessments of general cognitive ability are frequently needed by neuropsychologists, and many methods of estimating intelligence quotient (IQ) have been published. While these measures typically present overall correlations with the Wechsler Adult Intelligence Scale (WAIS) Full Scale IQ, it is tacitly acknowledged that these estimates are most accurate within 1 standard deviation of the mean and that accuracy diminishes moving toward the tails of the IQ distribution. However, little work has been done to systematically characterize proxy measures at the tails of the IQ distribution. Additionally, while these measures are all correlated with the WAIS, multiple proxy measures are rarely presented in one manuscript. The current article has two goals: (1) Examine various IQ proxies against Wechsler Adult Intelligence Scale (Third Version) scores, showing the overall accuracy of each measure against the gold standard IQ measure. This comparison will assist in selecting the best proxy measure for particular clinical constraints. (2) The sample is then divided into three groups (below, average, and above-average ability), and each group is analyzed separately to characterize proxy performance at the tails of the IQ distribution. Repeated measures multivariate analysis of variance compares the different proxy measures across ability levels. All IQ estimates are represented in tables so that they can be examined side by side.

Use of Complementary and Alternative Medicine by Males With Duchenne or Becker Muscular Dystrophy

Use of complementary and alternative medicine by males with Duchenne or Becker muscular dystrophy was examined using interview reports from caregivers enrolled in the population-based Muscular Dystrophy Surveillance, Tracking, and Research Network. Of the 200 caregivers interviewed, 160 (80%) reported “ever” using complementary and alternative medicine for their affected children. Mind-body medicine (61.5%) was most frequently used, followed by biologically based practices (48.0%), manipulative and body-based practices (29.0%), and whole medical systems (8.5%). Caregivers reporting use of whole medical systems had higher education and income levels compared with nonusers; affected males had shorter disease duration. Caregivers reporting use of mind-body medicine, excluding aquatherapy, had higher education level compared with nonusers. Overall, complementary and alternative medicine use was high; disease duration, education, and income levels influenced use. These findings have implications for developing clinical care protocols and monitoring possible interactions between complementary and alternative medicine and conventional medical therapies.

DRD4 genotype moderates the impact of parental problems on unresolved loss or trauma

In the current study we tested whether the dopamine receptor D4 (DRD4) genotype moderates the association of experienced parental problems during childhood (e.g., parental depression, marital discord) with unresolved loss or trauma during the Adult Attachment Interview. To test the specificity of this moderation the role of the serotonin transporter gene promoter (5-HTTLPR) was also examined. Subjects were 124 adopted adults (mean age 39 years). Participants with the DRD4-7 repeat (7R) allele who experienced parental problems had the highest scores for unresolved loss or trauma whereas participants with DRD4-7R who did not experience parental problems showed the lowest ratings. Among participants without DRD4-7R, the parental problems during childhood did not make a difference. 5-HTTLPR did not moderate the relation between parental problems and unresolved loss or trauma. Our study shows heightened susceptibility to environmental influences for carriers of the DRD4-7R allele, and suggests that the interplay between specific dopamine-related genes and family contexts leads to more or less successful coping with adverse childhood experiences.