The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders.

BACKGROUND: Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. METHOD: Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. RESULTS: Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. CONCLUSIONS: Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.

Towards the characterization and validation of alcohol use disorder subtypes: integrating consumption and symptom data.

BACKGROUND: There is evidence that measures of alcohol consumption, dependence and abuse are valid indicators of qualitatively different subtypes of alcohol involvement yet also fall along a continuum. The present study attempts to resolve the extent to which variations in alcohol involvement reflect a difference in kind versus a difference in degree. METHOD: Data were taken from the 2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions. The sample (51% male; 72% white/non-Hispanic) included respondents reporting past 12-month drinking at both waves (wave 1: n = 33644; wave 2: n = 25186). We compared factor mixture models (FMMs), a hybrid of common factor analysis (FA) and latent class analysis (LCA), against FA and LCA models using past 12-month alcohol use disorder (AUD) criteria and five indicators of alcohol consumption reflecting frequency and heaviness of drinking. RESULTS: Model comparison revealed that the best-fitting model at wave 1 was a one-factor four-class FMM, with classes primarily varying across dependence and consumption indices. The model was replicated using wave 2 data, and validated against AUD and dependence diagnoses. Class stability from waves 1 to 2 was moderate, with greatest agreement for the infrequent drinking class. Within-class associations in the underlying latent factor also revealed modest agreement over time. CONCLUSIONS: There is evidence that alcohol involvement can be considered both categorical and continuous, with responses reduced to four patterns that quantitatively vary along a single dimension. Nosologists may consider hybrid approaches involving groups that vary in pattern of consumption and dependence symptomatology as well as variation of severity within group.

Cannabis or alcohol first? Differences by ethnicity and in risk for rapid progression to cannabis-related problems in women.

BACKGROUND: Initiation of cannabis use typically follows alcohol use, but the reverse order does occur and is more common for African-Americans (AAs) than European-Americans (EAs). The aim of this study was to test for differences in the order of initiation of cannabis and alcohol use between AA and EA women and to determine whether order and ethnicity contribute independently to risk for rapid progression to cannabis-related problems. Method Data were drawn from structured psychiatric interviews of 4102 women (mean age = 21.6 years), 3787 from an all-female twin study and 315 from a high-risk family study; 18.1% self-identified as AA, 81.9% as EA. Ethnicity and order of initiation of cannabis and alcohol use were modeled as predictors of transition time from first use to onset of cannabis use disorder symptom(s) using Cox proportional hazards regression analyses. RESULTS: AA women were nearly three times as likely as EA women to initiate cannabis use before alcohol use. Using cannabis before alcohol [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.08-1.93] and AA ethnicity (HR 1.59, 95% CI 1.13-2.24) were both associated with rapid progression from first use to cannabis symptom onset even after accounting for age at initiation and psychiatric risk factors. CONCLUSIONS: The findings indicate that AA women are at greater risk for rapid development of cannabis-related problems than EA women and that this risk is even higher when cannabis use is initiated before alcohol use. Prevention programs should be tailored to the various patterns of cannabis use and relative contributions of risk factors to the development of cannabis-related problems in different ethnic groups.

Environmental influences predominate in remission from alcohol use disorder in young adult twins.

BACKGROUND: Familial influences on remission from alcohol use disorder (AUD) have been studied using family history of AUD rather than family history of remission. The current study used a remission phenotype in a twin sample to examine the relative contributions of genetic and environmental influences to remission. METHOD: The sample comprised 6183 twins with an average age of 30 years from the Australian Twin Registry. Lifetime history of alcohol abuse and dependence symptoms and symptom recency were assessed with a structured telephone interview. AUD was defined broadly and narrowly as history of two or more or three or more abuse or dependence symptoms. Remission was defined as absence of symptoms at time of interview among individuals with lifetime AUD. Standard bivariate genetic analyses were conducted to derive estimates of genetic and environmental influences on AUD and remission. RESULTS: Environmental influences alone accounted for remission in males and for 89% of influences on remission in females, with 11% due to genetic influences shared with AUD, which decreased the likelihood of remission. For women, more than 80% of influences on remission were distinct from influences on AUD, and environmental influences were from individual experiences only. For men, just over 50% of influences on remission were distinct from those on AUD, and the influence of environments shared with the co-twin were substantial. The results for the broad and narrow phenotypes were similar. CONCLUSIONS: The current study establishes young adult remission as a phenotype distinct from AUD and highlights the importance of environmental influences on remission.

Common genetic and environmental contributions to post-traumatic stress disorder and alcohol dependence in young women.

BACKGROUND: The few genetically informative studies to examine post-traumatic stress disorder (PTSD) and alcohol dependence (AD), all of which are based on a male veteran sample, suggest that the co-morbidity between PTSD and AD may be attributable in part to overlapping genetic influences, but this issue has yet to be addressed in females.MethodData were derived from an all-female twin sample (n=3768) ranging in age from 18 to 29 years. A trivariate genetic model that included trauma exposure as a separate phenotype was fitted to estimate genetic and environmental contributions to PTSD and the degree to which they overlap with those that contribute to AD, after accounting for potential confounding effects of heritable influences on trauma exposure. RESULTS: Additive genetic influences (A) accounted for 72% of the variance in PTSD; individual-specific environmental (E) factors accounted for the remainder. An AE model also provided the best fit for AD, for which heritability was estimated to be 71%. The genetic correlation between PTSD and AD was 0.54. CONCLUSIONS: The heritability estimate for PTSD in our sample is higher than estimates reported in earlier studies based almost exclusively on an all-male sample in which combat exposure was the precipitating traumatic event. However, our findings are consistent with the absence of evidence for shared environmental influences on PTSD and, most importantly, the substantial overlap in genetic influences on PTSD and AD reported in these investigations. Additional research addressing potential distinctions by gender in the relative contributions of genetic and environmental influences on PTSD is merited.

Alcohol problem recognition and help seeking in adolescents and young adults at varying genetic and environmental risk.

INTRODUCTION: Alcohol use disorder symptoms frequently occur in adolescents and younger adults who seldom acknowledge a need for help. We identified sociodemographic, clinical, and familial predictors of alcohol problem recognition and help seeking in an offspring of twin sample. METHOD: We analyzed longitudinal data from the Children of Alcoholics and Twins as Parents studies, which are combinable longitudinal data sources due to their equivalent design. We analyzed respondents (n=1073, 56.0% of the total sample) with alcohol use disorder symptoms at the baseline interview. Familial characteristics included perceptions of alcohol problems and help seeking for alcohol problems within the immediate family and a categorical variable indicating genetic and environmental risk. We used logistic regression to examine predictors of alcohol problem recognition and help seeking. RESULTS: Approximately 25.9% recognized their alcohol problems and 26.7% sought help for drinking. In covariate-adjusted analyses, help seeking among family members predicted problem recognition, several clinical characteristics predicted both problem recognition and help seeking, and familial risk predicted help seeking. Alcohol problem recognition mediated the association between alcohol use disorder symptoms and incident help seeking. CONCLUSIONS: Facilitating the self-recognition of alcohol use disorder symptoms, and perhaps the awareness of family members' help seeking for alcohol problems, may be potentially promising methods to facilitate help seeking.

The relationship between cannabis involvement and suicidal thoughts and behaviors.

BACKGROUND: In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology. METHODS: We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI. RESULTS: All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs]=1.28-2.00, p<0.01). Cannabis use and endorsing ≥3 symptoms were associated with unplanned (SANP; ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts (p>0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG=0.45) and environmental (rE=0.21) factors were responsible for the covariance between cannabis involvement and SI. CONCLUSIONS: Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders.

Health locus of control in late life: a study of genetic and environmental influences in twins aged 80 years and older.

The factor structure of health locus of control (Form A; K. A. Wallston, B. S. Wallston, & R. DeVellis, 1978) was examined in 420 octogenarians (M age = 83.2 years), and the contributions of genetic and environmental factors to health-control beliefs in 141 octogenarian twin pairs (71 identical, 70 same-sex fraternal) were estimated. Factor analyses reproduced previously proposed factors (Internal, Chance, and Powerful Others). Associations between health-control beliefs and life satisfaction, depression, and other health-related measures (e.g., self-rated health, outpatient contacts, and hospitalization), were modest. Quantitative genetic analyses revealed significant shared environmental influence on the Chance subscale, and significant familiality (attributable to a combination of genetic and shared environmental influences) on the Powerful Others subscale; there was no evidence of familiality on the Internal subscale.

Plasma concentrations of delta-9-tetrahydrocannabinol and impaired motor function.

Fifty-nine volunteer subjects were allowed to smoke marijuana cigarettes until a satisfactory level of 'high' was obtained. They then had blood samples taken 5, 30, 90 and 150 min following smoking after which they were tested with the roadside sobriety test. Attempts to correlate passing or failing on three coordination tests with plasma concentrations of delta-9-tetrahydrocannabinol (THC) showed that if concentrations measured at 5 min were ignored, failures were almost inevitably associated with plasma concentrations of THC above 25-30 ng/ml. Overall, 94% of subjects failed to pass the test 90 min after smoking and 60% after 150 min, despite the fact that by then plasma concentrations were rather low. It would seem that establishing a clear relation between THC plasma concentrations and clinical impairment will be much more difficult than it has been for alcohol.

delta 9-Tetrahydrocannabinol by GLC-MS validated radioimmunoassays of hemolyzed blood or serum.

A direct radioimmunoassay (RIA) of delta 9-tetrahydrocannabinol (delta 9-THC) in unextracted hemolyzed blood or serum is described. The dose-response curve in the range of 5-50 ng/mL (serum or blood) was linear on log-logit transformation and iterative weighted regression. Validation studies included testing for precision, accuracy and antibody specificity as well as confirmation of RIA results (marijuana smoker samples) by gas liquid chromatography-mass spectroscopy (GLC-MS). This routine method will greatly augment cannabinoid investigative programs.

Further considerations regarding inhibitory processes, working memory, and cognitive aging.

The present study explored the relationship between inhibitory processing (as indexed by identity negative priming in a letter-naming task), working memory, discourse processing, and cognitive aging effects. Consistent with several other recent reports, this study found evidence of intact inhibitory processing, as measured by negative priming, in older adults as well as younger adults. This intact negative priming occurred in conjunction with diminished working memory span and impaired memory in the discourse processing task in the same sample of older adults, further arguing against the likelihood that declines in these areas are caused by impairments in the inhibitory processes measured by negative priming. The implications of these results for theories of cognitive aging and possible reasons for inconsistent findings regarding negative priming effects among the elderly are discussed.

Willingness to take legal action in wrongful dismissal cases: perceptual differences between men and women.

146 business students with full-time work experience participated in a study of dismissal from employment. Based on self-ratings, men were more likely than women to favor court action in the event of dismissal.

Black plus blue equals pink: a case report of near fatal methemoglobinemia.

Methemoglobinemia, which is rarely seen in the emergency department, is an unusual cause of cyanosis. It often presents a peculiar and confusing picture to the clinician, and sometimes requires prompt recognition and treatment to prevent death. The following case report illustrates this point.

Significant developments in radioimmune methods applied to delta 9-THC and its 9-substituted metabolites.

Novel RIA's have been developed for marijuana detection. Modified simple techniques measure the "acute" metabolites in minute saliva, breath, and dried blood samples. Solid purified antibody matches the sensitivity and yields sensitivity values identical to liquid assays. The importance of the polar 9-substituted metabolites (9SM) of THC in acute users is shown by time course data that indicate their levels remain high in the critical post-intoxication period when delta 9-THC clears from the blood. Therefore a single-tube assay using solid-phase reagents was constructed to quantitate simultaneously delta 9-THC and 9SM. When delta 9-THC values are low or questionable in subject samples, 9SM would appear useful to confirm or refute acute marijuana use.