Right amygdala volume in adolescent and young adult offspring from families at high risk for developing alcoholism.

BACKGROUND: Neurobiological factors have been implicated in the increased susceptibility for developing alcohol dependence that offspring from alcoholic families exhibit. The P300 component of the event-related potential shows developmental changes during childhood and adolescence that appear to be related to risk status. The underlying structural changes that accompany these neurophysiological changes are not well understood. METHODS: Magnetic resonance imaging was used to measure cerebral, amygdala, and hippocampal volumes in 17 high-risk adolescent and young adult offspring from multiplex alcoholism families and 17 age-, gender-, and IQ-matched control subjects without a family history for alcoholism or other substance dependence. Twenty-two of the subjects are part of a longitudinal prospective study and have been followed an average of 7.3 years, making it possible to relate P300 developmental trajectories to structural volumes. RESULTS: High-risk adolescents and young adults showed reduced right amygdala volume in comparison with control subjects. Right amygdala volume was significantly correlated with visual P300 amplitude. CONCLUSIONS: Offspring from families having a high density of alcoholism differ in both neurophysiological and neuroanatomical characteristics that could not be explained by personal drinking history or particular childhood and adolescent psychopathology. Because the amygdala tends to increase in volume during childhood and adolescence, smaller volumes in high-risk children may indicate a developmental delay that parallels delays seen in visual P300 amplitude.

Maternal smoking and drinking during pregnancy and the risk for child and adolescent psychiatric disorders.

OBJECTIVE: To examine the relative importance of prenatal exposure to cigarettes and alcohol and familial/genetic susceptibility for alcohol dependence in the etiology of childhood psychopathology. METHOD: A longitudinal prospective study of 150 children/adolescents (51.3% male), who were at either high or low risk for developing alcohol dependence because of their familial loading for alcoholism, provided multiple diagnostic assessments (N = 318) of these subjects. High-risk families were identified through the presence of two adult alcoholic sisters; low-risk control families were selected from the community. Annual assessments of offspring from these families included an in-depth psychiatric interview of each child and his/her parent to determine the presence or absence of childhood disorders. Mothers were interviewed concerning their prenatal use of substances, and information was gathered concerning their personal and familial loading for psychiatric disorders. RESULTS: Using conventional logistic regression analyses, internalizing and externalizing disorders were found to be associated with familial loading for alcoholism and prenatal exposure to cigarettes and alcohol. In addition, a specialized statistical analysis, a multivariate confounder score approach, was conducted using familial risk status and the child's exposure to maternal prenatal use of alcohol and cigarettes. This analysis demonstrated that only one relationship between a single variable and a childhood disorder was significant while controlling for the other two variables: Oppositional disorder remained significant in association with familial risk status. Three additional analyses were performed to evaluate the effects of familial risk status, prenatal alcohol exposure and prenatal cigarette exposure on childhood psychopathology while controlling for two known risk factors (SES and parental ASPD) for externalizing disorders. Results of these analyses revealed that the only childhood disorder that was elevated was ADHD, and that this was the result of the familial risk variable only. CONCLUSIONS: Familial loading for alcohol dependence is an important risk factor for the development of childhood psychopathology and may account for the previously reported associations between prenatal exposure to nicotine and alcohol. Studies of substance abuse/dependence etiology and childhood psychopathology need to include consideration of both prenatal exposures and familial loading for alcohol dependence and other psychiatric disorders.

Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism.

BACKGROUND: With a longitudinal prospective design, the purpose of this study was 1) to assess, with survival analysis, the age of onset of drinking in relation to family history of alcoholism; 2) to examine the importance of selected neurobiological and psychosocial risk factors in predicting the onset to drink; and 3) to determine if the age of onset of substance dependence problems differed by risk group status. METHODS: One hundred twenty-five children and adolescents were evaluated annually (N = 638 evaluations), providing up to seven annual waves of longitudinal data. Survival analyses were performed to determine the age of onset of regular drinking and the age of onset for substance abuse/dependence. The age of onset of regular drinking outcome was modeled using familial density of alcoholism and four factors, which included neurobiological indices of development (postural sway and P300), personality characteristics, academic achievement, self-esteem, and trait anxiety. RESULTS: High-risk children/adolescents showed a significantly earlier age of onset of drinking and an earlier age of onset for substance abuse problems. Familial density of alcoholism predicted an earlier onset of drinking, as did having deficits in reading achievement, reduced P300 (visual and auditory), and greater postural sway for age. Higher scores on the Extraversion scale of the Junior version of the Eysenck Personality Inventory also predicted an earlier onset of drinking. CONCLUSIONS: Familial density of alcoholism (number of alcoholic first- and second-degree relatives) is an important predictor of adolescent alcohol initiation. Evidence is presented suggesting that part of the familial/genetic variation in outcome may be due to neurobiological factors and temperament.

Developmental changes in postural sway in children at high and low risk for developing alcohol-related disorders.

BACKGROUND: To utilize the power of latent growth analysis to evaluate changes in postural sway during development in children who are either at high or low risk for developing alcoholism. METHODS: A total of 629 assessments of postural sway have been performed in children and adolescents (n = 126) who were evaluated annually over a 7-year period. RESULTS: Latent curve models indicated that these children/adolescents show a linear decrease in sway with age. Moreover, significantly different rates of change in the amount of sway between high- and low-risk offspring were seen. With the exception of one of the four stances tested, high-risk boys consistently showed a slower rate of improvement with respect to the amount of sway exhibited compared to low-risk boys. In girls, similar rates of improvement with age were seen in high- and low-risk individuals, though in one stance the high-risk girls showed a deterioration (greater sway with increasing age). CONCLUSIONS: Previous reports of increased postural sway in high-risk offspring most likely reflect a developmental delay (high-risk children have greater sway than is appropriate for their age based on normative values by age).

Developmental delay in P300 production in children at high risk for developing alcohol-related disorders.

BACKGROUND: Reduction of P300 amplitude in children and adolescents at high risk for developing alcoholism has frequently been reported. It has been hypothesized that this reduction represents a developmental delay in reaching age-appropriate levels in P300 amplitude. Using latent growth analysis of longitudinal data obtained at yearly intervals, this study seeks to define normal growth, and determine if the pattern seen in high-risk children differs from that obtained in normal low-risk controls. METHODS: A total of 156 children from either high or low-risk families have been assessed multiple times (two-thirds more than 4 times) using both a clinical assessment (K-SADS) and ERP evaluation performed on the same day. A total of 635 separate assessments were available for modeling. RESULTS: Quadratic growth curves revealed a slower rate of change in P300 amplitude in high-risk than low-risk males. High-risk girls showed reduced visual P300 amplitude only when the presence of a K-SADS diagnosis was considered. No differences were seen for P300 latency. CONCLUSIONS: This study confirms the hypothesis that when reduction of P300 amplitude is seen in males at high risk for developing alcoholism, it is due to a developmental delay.

Psychopathology and achievement in children at high risk for developing alcoholism.

OBJECTIVE: To compare rates of psychopathology and academic achievement in children who were either at high or low risk for developing alcoholism and to determine whether academic deficits would predict prospectively the presence of psychopathology occurring within the next year. METHOD: Children and adolescents, aged 8 to 18 years, were evaluated as part of a longitudinal follow-up. Diagnoses obtained by using the Schedule for Affective Disorders and Schizophrenia for School-Age Children and grade-equivalent scores from the reading, spelling, and arithmetic sections of the Wide Range Achievement Test were determined at yearly intervals. RESULTS: High-risk offspring were more likely to have a diagnosable disorder. In addition, analyses using the mother's and father's diagnosis of alcoholism as a covariate showed higher hazard ratios for selected disorders (depression, affective disorder, attention-deficit/hyperactivity disorder, and conduct disorder), some of which were gender-dependent. Logistic regression analysis of achievement test scores demonstrated that reading and math scores predicted the presence of childhood psychopathology at the following annual evaluation. CONCLUSIONS: Children from pedigrees with a high density of alcoholism are at greater risk for developing psychopathology. Furthermore, observed deficits in academic performance may be considered an indicator of a developing diagnosable illness.

Behavioral inhibition in children from families at high risk for developing alcoholism.

OBJECTIVE: To determine whether children at risk for the development of adult alcohol dependence would show greater "behavioral inhibition" to the unfamiliar, an early childhood temperament characteristic. METHOD: One hundred peer play evaluations were conducted blindly with preschool children from families selected to be at high or low risk for developing alcohol dependence. Each child was paired with different children (same-sex pairs) in independent sessions to determine the stability of the behavioral response. RESULTS: High-risk children spent significantly more time staring at the other child during the peer play session while refraining from engaging in play, and significantly less time speaking to the other child. Significantly more time was spent proximal to the parent, but only on the first peer play session. These behaviors have been shown to be indicators of behavioral inhibition. CONCLUSIONS: These findings suggest that the presence of behavioral inhibition to the unfamiliar in childhood may be a risk factor for later development of alcohol dependence. While there is abundant evidence that childhood externalizing behaviors are risk factors for later development of substance dependence, the present results suggest that internalizing behaviors may be a pathway as well.