Impulsive and callous traits are more strongly associated with delinquent behavior in higher risk neighborhoods among boys and girls.

The purpose of the present study was to determine whether the effect of impulsive and callous personality traits on delinquent behavior varied across neighborhood context in a population-based, statewide sample of 85,000 Iowa schoolchildren ages 10-19. Two previous studies examining the association between impulsivity and delinquency across disadvantaged and affluent neighborhoods have yielded contrasting findings. Results of the present study suggested a robust moderating effect of neighborhood context on personality risk for delinquency. The relation between impulsivity and delinquency was greater in neighborhoods low in collective efficacy compared to neighborhoods high in collective efficacy. A similar interaction was found for callous personality traits, indicating the consistency of the moderating effect of neighborhood context on personality risk for delinquency. Gender differences were also examined, and results were replicated in a holdout sample.

Positive alcohol expectancies partially mediate the relation between delinquent behavior and alcohol use: generalizability across age, sex, and race in a cohort of 85,000 Iowa schoolchildren.

The extent to which positive alcohol expectancies mediated the association between delinquency and alcohol use, as well as whether age, sex, or race moderated this mediational relation, was examined in a population-based sample of Iowa schoolchildren (N = 85,301) from the 6th, 8th, and 11th grades. Positive alcohol expectancies were found to partially mediate the association between delinquency and alcohol use (alcohol use initiation, past-month drinking, and past-month binge drinking) across the full sample and in each age, sex, and racial subgroup. Evidence for moderated mediation was found for age and race but not for sex, which suggests that the magnitude of the relations among delinquency, positive alcohol expectancies, and alcohol involvement is different in younger versus older children and White, African American, Native American, Asian, and Hispanic youths but is similar in boys versus girls.

Association of a D2S2944 allele with depression specifically among those with substance abuse or antisocial personality.

Associations have previously been reported between a 124-bp allele at D2S2944 and recurrent, early-onset depression in women. These earlier reports also noted but did not emphasize a possible association between this allele and alcohol-specific depression. We have analyzed the Iowa Adoption Study data to test this association. D2S2944 allele typing was available for 247 subjects from the Iowa Adoption Studies. Information on lifetime affective, alcohol, drug, and antisocial personality (ASPD) disorders was available from a structured interview. We used logistic regression to analyze adjusted and interactive D2S2944 associations with depression. Controlling other risk factors, the 124-bp allele had a strong association with DSM-IV major depression specific to those with histories of alcohol abuse/dependence and/or ASPD. (Overlap between the two prevented further specification of the interaction.) The association was not gender-specific and was not limited to alcohol-related depressive episodes. This relationship appears stronger than the D2S2944 association previously reported for early-onset depression in women. We note that, in combination with additional liabilities towards depression in women and alcoholism/sociopathy in men, the 124-bp allele may provide a basis for the phenomenon of depressive spectrum illness proposed by Winokur.

Contributions of attachment style and perceived social support to lifetime use of illicit substances.

Research has shown insecure attachment style is associated with ineffective emotional regulation leading to maladaptive behaviors in adulthood. In the present study, we examined the association between attachment style and illicit substance use within a sample of adoptees (n=148). It was predicted that insecure attachment style would be associated with a higher incidence of lifetime illicit substance use and that perceived social support would mediate this association. Logistic regression analyses showed higher prevalence of illicit substance use among both insecure attachment groups as compared to the secure group. No difference was found between the two insecure types. Perceived social support was found to mediate the association between attachment style and illicit substance use for the insecure-preoccupied group only. The findings from the present study further implicate attachment style in the risk for illicit substance use, as well as preventions designed to identify those at risk for use.

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 Cloninger's Type II or Babor's Type B.

Adoption Studies.

Researchers use adoption studies to determine the contributions of genetic and environmental factors to the development of alcohol problems. These studies generally compare the outcomes of adoptees who have biological parents with alcohol problems and who grow up in various adoptive environments with the outcomes of adoptees without such family backgrounds but raised in similar environments. Using certain statistical approaches, adoption studies also allow for the evaluation of specific gene-environment interactions in determining an outcome such as alcoholism. To obtain data that allow meaningful and generalizable conclusions, however, scientists must select a representative group of study subjects, obtain valid information about these subjects from a wide variety of sources, and consider biases inherent in adoption practices.

Cluster analysis of childhood temperament data on adoptees.

Cluster analysis is used with behavioral data on 162 adoptees to assess temperament and to test the validity of the temperament typologies described by Thomas and Chess. Data are divided into two groups by sex. Results concur with the Thomas-Chess findings in identifying three main temperament groups: difficult, easy, and slow to warm up. Membership in the difficult group predicted later childhood behavior disorder in both sexes. Differing environmental factors associated with difficulty for males and for females are considered, and directions for further investigation are suggested.

Adult outcomes of attention deficit hyperactivity disorder and conduct disorder: are the risks independent or additive?

METHODS: Data were obtained from a longitudinal study sample of 754 adoptees and categorized based on review of the available adoption agency, medical, and psychiatric records of the biological parents. Categorical data were analyzed using chi2 or Fisher's exact tests, as appropriate. Logistic regression analyses were used to assess the relative contribution of variables. RESULTS: There was not a statistically significant difference in the frequency or type of self-reported adult disruptive behavior, arrests, jail stays, felony arrests, or frequency of conduct disorder (CD) when inattentiveness, impulsivity, and hyperactivity were analyzed individually. The contributions of attention deficit hyperactivity disorder (ADHD) were independent and no additional increased risk for future illegal behavior was conferred by the combination of the disorders. While the effect of CD on illegal behavior was correlated with substance abuse and dependence, ADHD continued to be a significant contributor after controlling for substance abuse and dependence. CONCLUSIONS: Data indicated that ADHD and CD are related but different disorders conferring risk for adult illegal behavior or arrest. In this sample, inattention was the most common domain impaired among those with ADHD, followed closely by hyperactivity, with impulsivity reported least often among those endorsing symptoms of ADHD.

Secondary prevention of schizophrenia: utility of standardized scholastic tests in early identification.

BACKGROUND: Given the enormous societal burden of schizophrenia, there has been a growing interest in its prevention during the past decade. Early detection and prompt treatment may improve outcome in schizophrenia. In this study, we examine the value of using pre-morbid cognitive impairment in early detection. METHODS: Standardized achievement tests Iowa Test of Basic Skills (ITBS) and Iowa Tests of Educational Development (ITED) at Grades 4, 8 and 11 were examined in 70 patients with schizophrenia and 147 comparison subjects without schizophrenia. The majority of comparison subjects later developed another major mental illness such as substance abuse or mood disorder. Receiver operating characteristic curves were used to test the efficiency and accuracy of pre-morbid cognitive tests for differentiating adolescents who will later develop schizophrenia from those who remain well or develop another mental illness. RESULTS: Although schizophrenia patients had lower mean percentile ranks than comparison subjects in every ITBS/ITED sub-test, these differences were only associated with small increases in risk for schizophrenia. Standardized scholastic tests achieved moderate sensitivity and specificity, and enhanced the detection of schizophrenia by three to five fold. However, positive predictive values were low. ITBS/ITED scores alone cannot be used in screening the general population, given the low positive predictive values. CONCLUSION: Combining ITBS/ITED scores with other risk factors, such as family history, may lead to more efficient early detection. Our findings illustrate the challenges facing the secondary prevention of schizophrenia. Priority should be given to developing efficient and accurate methods of early detection in order to reduce the dangers of making erroneous false positive diagnoses, and to decrease exposure to unnecessary treatment during the testing of early interventions.

Biology-environment interaction and evocative biology-environment correlation: contributions of harsh discipline and parental psychopathology to problem adolescent behaviors.

Using an adoption paradigm, the Bioecological Model of development proposed by Bronfenbrenner and Ceci in 1994 was tested by concurrently modeling for biology-environment interaction and evocative biology-environment correlation. A sample of 150 adult adoptees (ages, 18-45 years) provided retrospective reports of harsh adoptive parent discipline, which served as the environmental independent variables. Birth parent psychopathology served as the biological predictor. The dependent variables were retrospective adoptee and adoptive parent reports on adolescent aggressive and conduct-disordered behaviors. Finally, adoptees were classified as experiencing contextual environmental risk using the presence of two or more adverse factors in the adoptive home (e.g., adoptive parent psychopathology) as the cutoff. The contextual environment was found to moderate the biological process of evocative biology-environment correlation, providing empirical support for the Bronfenbrenner and Ceci (1994) Bioecological Model.

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.

The association of a HOPA polymorphism with major depression and phobia.

Thyroid hormone has a prominent role in the development and homeostasis of the central nervous system (CNS). Consequently, genes participating in thyroid hormone receptor (THR)-mediated signal transduction are prime candidates for neuropsychiatric illness susceptibility factors. Previously, we have associated exonic polymorphisms in a Xq13 thyroid receptor coactivator named HOPA with a modest increase in vulnerability to a broad spectrum of neuropsychiatric illness, including depression, psychosis, and hypothyroidism. In order to test and extend these findings, we have now examined the relationship between HOPA polymorphisms and neuropsychiatric illness in a cohort of Iowa adoptees. Consistent with our prior findings, HOPA polymorphisms were associated with an increased risk for major depression. There was suggestive evidence that the increased psychiatric morbidity in these subjects could represent epistasis, e.g., an interaction between the HOPA variant and a genetic diathesis for another psychiatric condition such as biologic parent antisocial behavior. Information about biologic parent behavior and the adoptive home environment was used to determine depressive symptoms attributable to gene-environment interaction. HOPA variant subjects continued to show significant differences in depressive symptoms when controlling for gene-environment interaction. Finally, because obesity is associated with hypothyroidism and HOPA polymorphisms are associated with hypothyroidism, we analyzed weight with respect to HOPA allele status. We found that that HOPA polymorphisms were associated with increased risk for obesity (P <.001). In summary, we conclude that HOPA polymorphisms may be a moderate risk factor for increased susceptibility to a broad spectrum of neuropsychiatric illness and hypothesize that the type of illness manifested might be related to a separate genetic diathesis.

Associations of the serotonin transporter promoter polymorphism with aggressivity, attention deficit, and conduct disorder in an adoptee population.

Prior studies of the Iowa Adoption cohorts have demonstrated that the degree of adoptee aggressiveness and conduct disorder has a significant genetic component. Other studies have implicated the neurotransmitter serotonin or polymorphisms in the serotonin transporter gene (5HTT) as an important source of variability in "externalizing" behaviors such as aggressivity, conduct disorder, and attention deficit-hyperactivity disorders (ADHD). Following this lead, we genotyped a subgroup of adoptees (n = 87) at high risk for these kinds of disorders with respect to the serotonin-transporter-linked promoter region (5HTTLPR) polymorphism, and used ordinal logistic regression to conduct an association study. Primary analysis failed to detect a main effect between 5HTTLPR status and subscales of aggressivity, conduct disorder, or attention deficit. However, when biologic parent status and sex of proband were considered, certain interactions between 5HTTLPR and other genetic risk factors were evident. One type of interaction with the LL variant of 5HTTLPR increased externalizing behavior in individuals with antisocial biologic parentage; a second interaction with one or more 5HTTLPR short variants (SS or SL) appeared to increase externalizing behaviors in conjunction with a genetic diathesis for alcoholism. Gender of adoptee also appeared to interact with 5HTTLPR. Male individuals with the short variant were more likely to have higher symptom counts for conduct disorder, aggressivity, and ADHD. In contrast, among females, the short variant (SS, SL) was associated with lower levels of such behavior. The results support the hypothesis that gene-biological family history interactions are involved in the externalizing behaviors studied and constitute interesting findings for future replication.