Biomedical subjects

Stephen M Malone

Publications and source records attributed to Stephen M Malone.

10 recordsLinked to original sources

PubMed2006

Decomposing delta, theta, and alpha time-frequency ERP activity from a visual oddball task using PCA.

OBJECTIVE: Time-frequency (TF) analysis has become an important tool for assessing electrical and magnetic brain activity from event-related paradigms. In electrical potential data, theta and delta activities have been shown to underlie P300 activity, and alpha has been shown to be inhibited during P300 activity. Measures of delta, theta, and alpha activity are commonly taken from TF surfaces. However, methods for extracting relevant activity do not commonly go beyond taking means of windows on the surface, analogous to measuring activity within a defined P300 window in time-only signal representations. The current objective was to use a data driven method to derive relevant TF components from event-related potential data from a large number of participants in an oddball paradigm. METHODS: A recently developed PCA approach was employed to extract TF components [Bernat, E. M., Williams, W. J., and Gehring, W. J. (2005). Decomposing ERP time-frequency energy using PCA. Clin Neurophysiol, 116(6), 1314-1334] from an ERP dataset of 2068 17 year olds (979 males). TF activity was taken from both individual trials and condition averages. Activity including frequencies ranging from 0 to 14 Hz and time ranging from stimulus onset to 1312.5 ms were decomposed. RESULTS: A coordinated set of time-frequency events was apparent across the decompositions. Similar TF components representing earlier theta followed by delta were extracted from both individual trials and averaged data. Alpha activity, as predicted, was apparent only when time-frequency surfaces were generated from trial level data, and was characterized by a reduction during the P300. CONCLUSIONS: Theta, delta, and alpha activities were extracted with predictable time-courses. Notably, this approach was effective at characterizing data from a single-electrode. Finally, decomposition of TF data generated from individual trials and condition averages produced similar results, but with predictable differences. Specifically, trial level data evidenced more and more varied theta measures, and accounted for less overall variance.

Adolescent↗

PubMed2006

Using the brain P300 response to identify novel phenotypes reflecting genetic vulnerability for adolescent substance misuse.

We used a novel approach to identify candidate alternative phenotypes for investigating genetic influence underlying substance use disorders (SUDs) in adolescents. The existing literature suggests that P300 amplitude reduction (P3-AR) observed in brain event-related potentials is associated with risk for SUDs generally, not just alcoholism. Using data from a community-based sample of 17-year-old male and female twins, we fit biometric models to P3 amplitude data to show that it is strongly heritable, especially in boys. The extant evidence coupled with our findings strongly supports treating P3-AR as an endophenotype indexing SUD risk. We then examined a set of 15 potential alternative phenotypes (e.g., frequent use of cannabis) to determine whether they were associated with P3-AR. The results indicated that almost all of these alternative phenotypes were associated with P3-AR, with larger effect sizes observed for boys. Given the strong association of these use phenotypes with P3-AR, which is itself an index of genetic risk for SUDs, we conclude that these use phenotypes may provide tools for finding vulnerability genes in adolescents who have yet to pass through the age of risk for SUDs.

Adolescent↗

PubMed2006

P300 amplitude as an indicator of externalizing in adolescent males.

Reduced P300 amplitude is reliably found in individuals with a personal or family history of alcohol problems. However, alcoholism is part of a broader externalizing spectrum that includes other substance use and antisocial disorders. We hypothesized that reduced P300 is an indicator of the common factor that underlies disorders within this spectrum. Community males (N=969) were assessed at age 17 in a visual oddball task. Externalizing was defined as the common factor underlying symptoms of alcohol dependence, drug dependence, nicotine dependence, conduct disorder, and adult antisocial behavior. A robust association was found between reduced P300 amplitude and the externalizing factor, and this relation accounted for links between specific externalizing disorders and P300. Our findings indicate that reduced P300 amplitude is an indicator of the broad neurobiological vulnerability that underlies disorders within the externalizing spectrum.

Adolescent↗

PubMed2005

Etiological contributions to heavy drinking from late adolescence to young adulthood.

The authors examined genetic and environmental contributions to stability and change in heavy drinking from late adolescence to young adulthood in a sample of 1,152 twin pairs. In men, heavy drinking was similarly heritable at ages 17 (h2=.57) and 20 (h2=.39), and its stability owed primarily to common genetic factors. In women, heavy drinking was less heritable than in men at ages 17 (h2=.18) and 20 (h2=.30) and its stability was primarily due to enduring shared environmental influences. P3 amplitude, an event-related brain potential marker of alcoholism risk, was less predictive of heavy drinking in women than in men, providing further support for the proposition that biological factors have less impact on heavy drinking in young adult women than in young adult men.

Adolescent↗

PubMed2004

Genetic and environmental influences on antisocial behavior and alcohol dependence from adolescence to early adulthood.

Genetic and environmental influences on symptoms of adult antisocial behavior (AAB) and alcohol dependence at ages 17, 20, and 24 were examined cross-sectionally and longitudinally in 188 monozygotic and 101 dizygotic male twin pairs. A moderate genetic influence on both AAB and alcohol dependence was found at each age, with a substantial proportion of this influence common to the two disorders, suggesting they share susceptibility genes. Biometrical models showed that continuity effects accounted for most of the stable variance in symptoms of both AAB and alcohol dependence, indicating that genetic and environmental effects associated with each of these disorders were similar at each age. Significant cross-lag effects (effects of alcohol dependence contributing to variance in AAB and vice versa) were observed at ages 20 and 24 for both disorders. The largest and theoretically most interesting of these effects indicated that one sixth of the genetic influence on AAB at age 20 was due to genetic effects associated with alcohol dependence at age 17. Thus, alcohol dependence symptoms at age 17 in particular had an effect on antisocial behavior symptoms at age 20, suggesting that alcohol involvement in adolescence may ensnare otherwise desisting youth in persistent antisocial behavior.

Adolescent↗

PubMed2004

Psychiatric disorders among offspring of depressed mothers: associations with paternal psychopathology.

OBJECTIVE: The association between maternal depression and offspring dysfunction is well documented; however, little attention has been paid to psychopathology in the partners of these depressed mothers or to how paternal psychopathology might influence the relationship between maternal depression and offspring dysfunction. The purpose of this study was to explore whether major depression and/or antisocial behavior tended to occur more frequently among partners of depressed mothers (compared to partners of nondepressed mothers) and to examine how these paternal disorders related to offspring psychopathology. METHOD: Participants were drawn from the Minnesota Twin Family Study, a community-based study of twins and their parents. Depressed and nondepressed mothers, their partners (the biological fathers of the twins), and their 17-year-old offspring were included. Structured interviews were used to assess participants for the presence of major depression, conduct disorder, and adult antisocial behavior. RESULTS: Depressed mothers tended to partner with antisocial fathers. Depression in mothers and antisocial behavior in fathers were both significantly and independently associated with offspring depression and conduct disorder. No interactions of the parental diagnoses with each other or with the gender of the offspring were found. CONCLUSIONS: Many offspring of depressed mothers experience the additional risk of having an antisocial father. The implications of these findings for risk among the offspring of depressed mothers are discussed.

Adolescent↗

PubMed2003

Substance use disorders, externalizing psychopathology, and P300 event-related potential amplitude.

We hypothesize the existence of an inherited predisposition for a spectrum of behaviors and traits characterized by behavioral disinhibition. This externalizing spectrum includes childhood disruptive disorders, antisocial behavior, substance use disorders, personality traits related to behavioral undercontrol, and the precocious expression of problem behavior. We further hypothesize that a genetically influenced central nervous system diathesis underlies this spectrum and is reflected in reduced P300 amplitude in a visual oddball event-related potential task. A review of evidence bearing on the model is derived from findings from the Minnesota Twin Family Study, a population-based, longitudinal investigation of twin youth. These findings indicate that the collection of attributes related to behavioral disinhibition is familial, heritable, and interrelated. Evidence supporting P3 amplitude reduction (P3-AR) as an index of genetic vulnerability for this externalizing spectrum includes its association with (a) familial risk for substance use and antisocial personality disorders, (b) diagnoses of childhood disruptive disorders and substance use disorders, (c) early onset of undersocialized behavior, and (d) quantitative phenotypes related to externalizing problems. In addition, the development of substance use disorders over a 3-year period is associated with P3-AR measured prior to their expression. These findings suggest that P3-AR indexes one aspect of the genetic diathesis for a spectrum of externalizing problem behavior.

Adolescent↗

PubMed2002

P3 event-related potential amplitude and the risk for disinhibitory disorders in adolescent boys.

BACKGROUND: The children of parents who abuse alcohol typically show reduced amplitude of the P3 event-related potential wave. We determined if this effect was present in a population-based sample of older adolescent boys, whether it was associated with paternal antisocial personality and drug use, and whether it appeared in youth with childhood externalizing and substance use disorders. METHODS: A statewide sample of 502 male youth, identified from Minnesota birth records as members of twin pairs, had their P3 amplitude measured, using a visual oddball paradigm when they were approximately 17 years old. Structured clinical interviews covering attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder, antisocial personality disorder, and substance use disorders were administered in person to the youth and his parents at the time of the P3 assessment and again to the youth 3 years later. RESULTS: Reduced P3 was associated with disorders and paternal risk for disorders, reflecting a behavioral disinhibition spectrum that included attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, antisocial personality disorder, alcoholism, nicotine dependence, and illicit drug abuse and dependence. Reduced P3 at age 17 predicted the development of substance use disorders at age 20. Most effect sizes associated with these group differences exceeded 0.70, indicating medium to moderately large group differences. Maternal alcoholism and substance use during pregnancy were unrelated to P3 amplitude in offspring. CONCLUSION: Small amplitude P3 may indicate genetic risk for a dimension of disinhibiting psychiatric disorders, including childhood externalizing, adult antisocial personality disorder, and substance use disorders.

Adolescent↗

PubMed2002

Drinks of the father: father's maximum number of drinks consumed predicts externalizing disorders, substance use, and substance use disorders in preadolescent and adolescent offspring.

BACKGROUND: The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses. METHODS: Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population-based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11-year-old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures. RESULTS: Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism. CONCLUSIONS: Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.

Adolescent↗

PubMed2002

Error rate on the antisaccade task: heritability and developmental change in performance among preadolescent and late-adolescent female twin youth.

We examined heritability of error rate on the antisaccade task among female twin youths. This task appears to be sensitive to prefrontal functioning, providing a measure of individual differences in inhibitory control associated with genetic risk for schizophrenia. The sample consisted of 674 11-year-olds and 616 17-year-olds, comprising the two cohorts of female twins from the Minnesota Twin Family Study, a population-based investigation of substance abuse and related psychopathology. We used biometric model-fitting methods to determine the relative magnitude of genetic and environmental influences on performance. In both age cohorts, the best fitting model contained additive genes and nonshared environment. Despite substantial age-related differences in mean performance levels (effect size = .81), additive genes accounted for greater than half the variance in performance in both age cohorts. These results are consistent with the hypothesis that antisaccade error rate might serve as an endophenotype for behavior disorders reflecting frontal lobe dysfunction or problems with inhibitory control.

Adolescent↗