Psychopathology in offspring from multiplex alcohol dependence families with and without parental alcohol dependence: a prospective study during childhood and adolescence

Multiplex families ascertained through multiple alcohol dependent individuals appear to transmit alcohol and drug use disorders at higher rates than randomly selected families of alcoholics. Our goal was to investigate the risk of developing specific psychiatric diagnoses during childhood or adolescence in association with familial risk status (high-risk [HR] or low-risk [LR]) and parental diagnosis. Using a prospective longitudinal design, HR offspring from three generation multiplex alcohol dependence families and LR control families were followed yearly. Data analysis was based on consensus diagnoses from 1738 yearly evaluations conducted with the offspring and a parent using the K-SADS, and separately modeled the effects of familial susceptibility and exposure to parental alcohol dependence. Multiplex family membership and parental alcohol and drug dependence significantly increased the odds that offspring would experience some form of psychopathology during childhood or adolescence, particularly externalizing disorders. Additionally, parental alcohol dependence increased the odds that adolescent offspring would have major depressive disorder (MDD). While it is well known that parental substance dependence is associated with externalizing psychopathology, the increased risk for MDD seen during adolescence in the present study suggests the need for greater vigilance of these children.     

Neurodevelopmental patterns of visual P3b in association with familial risk for alcohol dependence and childhood diagnosis.

BACKGROUND: The P3b component of the event-related potential (ERP) has frequently been reported to be reduced in children and adolescents at high risk for developing alcoholism relative to control children and adolescents without familial loading for alcohol dependence. P300 amplitude changes during development for all children. Previously it has been shown that high-risk offspring display a pattern in which the amplitude is lower at age 8 with a smaller rate of change during adolescence. METHODS: Admixture analysis was applied to data obtained for those children and adolescents having five or more annual assessments of ERPs to determine if multiple P3b growth patterns exist. The P3b amplitude patterns obtained were related to risk status, concurrent presence of childhood psychopathology (internalizing or externalizing), and age of onset to develop a diagnosis. RESULTS: A pattern characterized by lower P3b amplitude at study entry and a slower rate of change during child and adolescent development (pattern 3) was most often associated with high-risk status in boys and high-risk status in combination with the presence of a childhood diagnosis in girls. Pattern 3 was significantly related to the overall presence of childhood psychopathology (internalizing or externalizing) and to the presence of an Axis I diagnosis at young adult follow-up. CONCLUSIONS: The developmental pattern previously described for offspring at high risk for developing alcoholism because of their familial/genetic background was confirmed. Admixture analysis has refined this observation and suggests that among all children and adolescents tested, three developmental patterns can be identified, one of which is most often seen in association with male high-risk children and adolescents.     

Cerebellar volume in offspring from multiplex alcohol dependence families.

BACKGROUND: Increased susceptibility for developing alcohol dependence (AD) might be related to structural differences in brain circuits that influence the salience of rewards and/or modify the efficiency of information processing. The role of the cerebellum in regulating cognitive functions is being increasingly recognized along with its well-known influence on motor performance. Additionally, developmental changes in cerebellar volume during adolescence have been reported. METHODS: Magnetic resonance imaging was used to measure the cerebellum in 17 high-risk adolescent and young adult offspring from multiplex alcohol dependence families and 16 control subjects matched for gender, age, and IQ. RESULTS: High-risk (HR) adolescents/young adults showed increased total cerebellum volume and total grey in comparison with control subjects. Age-related decreases in total grey volume were seen with age, a pattern that was not seen in HR offspring. CONCLUSIONS: Offspring from multiplex families for AD manifest genetic susceptibility by having larger cerebellar volume, which seems to be related to lesser grey matter pruning for age. Larger cerebellar volumes in adult obsessive compulsive disorder (OCD) patients have been reported. This suggests a possible similarity in structural underpinnings for alcohol dependence and OCD.     

Psychopathology in offspring from families of alcohol dependent female probands: A prospective study

Background

Despite the importance of understanding the long-term outcome for children of alcohol dependent (AD) women, the available literature is largely based on offspring of AD fathers and few have utilized prospective designs that include child, adolescent and young adult assessments. Multiplex AD families in which multiple cases of AD are present provide an ideal setting for understanding developmental variants of the adult phenotype.

Method

Offspring from multiplex AD families identified through the mother or control families were evaluated multiple times during childhood and followed to young adulthood. Familial risk status and the presence of specific child/adolescent disorders were used as predictors of substance use disorder outcome by young adulthood.

Results

Offspring who were members of maternal multiplex families had elevated rates of child and young adulthood disorders. High risk offspring of alcohol dependent women were at increased risk for externalizing (Conduct Disorder and ADHD) and internalizing disorders (Major Depressive Disorder (MDD) and Anxiety Disorders). By young adulthood, offspring from these multiplex families had significantly greater odds of developing alcohol abuse or dependence (odds ratio [OR] = 3.63 [CI 1.36-9.64]) and drug abuse or dependence (OR = 4.23 [CI 1.73-10.32]). The prospective design of the study revealed that specific childhood disorders (Conduct Disorder, ADHD, MDD) increased the odds of subsequent development of substance use disorder (SUD).

Conclusions

Multiplex familial risk for alcohol dependence is a significant predictor of substance use disorders by young adulthood. Familial risk and an earlier childhood disorder may set the stage for later development of SUD.     

Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy

OBJECTIVE: To address the putative association between attention-deficit hyperactivity disorder (ADHD) and prenatal exposure to maternal cigarette smoking, drugs of abuse, and alcohol attending to potential confounding by familial ADHD, maternal depression, conduct disorder, and indicators of social adversity in the environment. METHOD: A retrospective, hospital-based, case-control study was conducted with 280 ADHD cases and 242 non-ADHD controls of both genders. The case and control children and their relatives were systematically assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of prenatal exposure to substance use and ADHD. RESULTS: ADHD cases were 2.1 times (95% confidence interval = 1.1-4.1;p = .02) more likely to have been exposed to cigarettes and 2.5 times (95% confidence interval = 1.1-5.5; p = .03) more likely to have been exposed to alcohol in utero than were the non-ADHD control subjects. Adjustment by familial psychopathology, Rutter's indicators of social adversity, and comorbid conduct disorder did not account for the effect of prenatal exposure to alcohol or the products of cigarettes. CONCLUSIONS: ADHD may be an additional deleterious outcome associated with prenatal exposure to alcohol independently of the association between prenatal exposure to nicotine and smoke products and other familial risk factors for the disorder.     

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.     

Cholinergic receptor gene (CHRM2) variation and familial loading for alcohol dependence predict childhood developmental trajectories of P300

P300 amplitude in childhood predicts substance use disorders by young adulthood. Trajectories of visual P300 amplitude show an association between low amplitude P300 and familial risk for alcohol dependence (AD). Variation in the cholinergic muscarinic receptor gene (CHRM2) has previously been associated with P300 amplitude and AD. The present study used group based trajectory modeling of auditory P300 data collected longitudinally from offspring in families with and without familial loading for AD to determine if specific trajectories would be associated with familial risk and CHRM2 variation. Trajectory modeling confirms previous reports of an association between the low visual P300 trajectory with high familial risk in male offspring. This association was detected in offspring in the 8–12 age range, but not in 13–18 or 19–29 year olds or in high-risk female offspring. CHRM2 association analysis with P300 finds 8–12 year olds who are homozygous for the T allele of rs1824024 are 2.6 times more likely to follow a P300 trajectory characterized by lower and slower change regardless of familial loading. Combining the odds for being male and having a TT genotype results in odds of 6.5 that individuals will follow the low P300 trajectory.     

A 21-year longitudinal analysis of the effects of prenatal alcohol exposure on young adult drinking

BACKGROUND: Prenatal alcohol exposure may be a risk factor for the development of alcohol problems in humans. METHODS: We use data beginning with interviews of women in prenatal care at midpregnancy to predict alcohol use and alcohol-related problems in their offspring now aged 21 years. Maternal drinking during pregnancy was assessed from November 4, 1974, through October 2, 1975, along with measures of maternal smoking, use of caffeine and other drugs, and demographic factors. Family history of alcohol problems was assessed from interviews with parents when offspring were 14 years of age and updated when offspring were 21 years of age. Measures of parental use of alcohol and other drugs and many aspects of the family environment were assessed at 7 different ages, prenatally through 21 years. Young adult offspring (age, 21 years [N = 433]) provided self-reports of drinking quantity and frequency and completed the Alcohol Dependence Scale as a measure of alcohol-related problems and dependence. RESULTS: Univariate, partial least squares, and regression analyses indicate that prenatal alcohol exposure is significantly associated with alcohol problems at 21 years of age. The relationship persists independent of the effects of family history of alcohol problems, nicotine exposure, other prenatal exposures, and postnatal environmental factors including parental use of other drugs. Prenatal nicotine exposure was not associated with alcohol problems by offspring at 21 years of age. CONCLUSIONS: Prenatal alcohol exposure is a risk factor for the development of drinking problems in humans. Potential mechanisms for the role of fetal exposure and the development of alcohol problems deserve study.     

Volumetric Differences in Cerebellar Lobes in Individuals from Multiplex Alcohol Dependence Families and Controls: Their Relationship to Externalizing and Internalizing Disorders and Working Memory

Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence and related substance use disorders. Greater susceptibility for these disorders may be related to cerebellar morphology. Because posterior regions of the cerebellum are associated with cognitive abilities, we investigated whether high-risk offspring would display regionally specific differences in cerebellar morphology and whether these would be related to working memory performance. The relationship to externalizing and internalizing psychopathology was of interest because cerebellar morphology has previously been associated with a cognitive affective syndrome. A total of 131 participants underwent magnetic resonance imaging (MRI) with volumes of the cerebellar lobes obtained with manual tracing. These individuals were from high-risk (HR) for alcohol dependence families (N?=?72) or from low-risk (LR) control families (N?=?59). All were enrolled in a longitudinal follow-up that included repeated clinical assessments during childhood and young-adulthood prior to the scan that provided information on Axis I psychopathology. The Working Memory Index of the Wechsler Memory Scale was given at the time of the scan. Larger volumes of the corpus medullare and inferior posterior lobes and poorer working memory performance were found for the HR offspring relative to LR controls. Across all subjects, a significant positive association between working memory and total volume of corpus of the cerebellum was seen, controlling for familial risk. Presence of an internalizing or externalizing disorder interacting with familial risk was also associated with volume of the corpus medullare.     

Corpus callosum and visual cortex of mice with deletion of the NMDA-NR1 receptor. II. Attenuation of prenatal alcohol exposure effects

Offspring of transgenic mice with deletion of the NMDA-NR1 (NR1) receptor received prenatal alcohol exposure during most of gestation. Before and after birth, offspring were sacrificed in order to examine the morphological consequences of the prenatal exposure. Previously, we reported that the dendritic arborization of corpus callosum projection neurons (CCpn) in visual cortex was abnormal in rats given prenatal alcohol exposure; the effects were dose-dependent [Neurotoxicol. Teratol. 24 (2002) 719-732]. The same parameters were examined in the transgenic mice. Crystals of DiI were placed into the CC of mice at different ages that had been prenatally exposed to alcohol. Controls included untreated transgenic mice, and transgenic mice with the same nutritional and handling stressors. Compared to Controls, prenatal alcohol exposure caused the NR1+/+ mice to expand the dendritic arbor of CCpn in visual cortex. The dendritic arbors had increased branch numbers and length; these increases were dose-dependent. In contrast, the prenatally exposed NR1-/- mice showed normal dendritic arbors with all prenatal alcohol doses. In addition, prenatal alcohol exposure was found to have morbidity and teratogenic effects on offspring. In seven separate indicators of the effects of prenatal alcohol exposure, only one indicator was present but reduced in NR1-/- offspring, indicating that total deletion of the NMDA-NR1 receptor throughout development largely blocks but sometimes attenuates the effects of prenatal alcohol exposure. Similarly, in seven separate indicators of the effects of prenatal alcohol exposure, five indicators were attenuated in NR1+/- compared to NR1+/+ offspring, although affected more than in NR1-/-; this suggests a gene-dose effect. The results indicate that functional NMDA-NR1 receptors are necessary for the neurotoxic and teratogenic effects of prenatal alcohol exposure. This study will aid in understanding how the NMDA receptors play an important role in prenatal alcohol effects on brain development.     

A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependent probands

BACKGROUND: Alcohol dependence tends to aggregate within families. We analyzed data from the family collection of the Collaborative Study on the Genetics of Alcoholism to quantify familial aggregation using several different criterion sets. We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability. DESIGN: Age-corrected lifetime morbid risk was estimated in adult first-degree relatives of affected probands and control subjects for selected disorders. Diagnostic data were gathered by semistructured interview (the Semi-Structured Assessment for the Genetics of Alcoholism), family history, and medical records. Rates of illness were corrected by validating interview and family history reports against senior clinicians' all sources best estimate diagnoses. Sex, ethnicity, comorbidity, cohort effects, and site of ascertainment were also taken into account. RESULTS: Including data from 8296 relatives of alcoholic probands and 1654 controls, we report lifetime risk rates of 28.8% and 14.4% for DSM-IV alcohol dependence in relatives of probands and controls, respectively; respective rates were 37.0% and 20.5% for the less stringent DSM-III-R alcohol dependence, 20.9% and 9.7% for any DSM-III-R diagnosis of nonalcohol nonnicotine substance dependence, and 8.1% and 5.2% for antisocial personality disorder. Rates of specific substance dependence were markedly increased in relatives of alcohol-dependent probands for cocaine, marijuana, opiates, sedatives, stimulants, and tobacco. Aggregation was also seen for panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and major depression. CONCLUSIONS: The risk of alcohol dependence in relatives of probands compared with controls is increased about 2-fold. The aggregation of antisocial personality disorder, drug dependence, anxiety disorders, and mood disorders suggests common mechanisms for these disorders and alcohol dependence within some families. These data suggest new phenotypes for molecular genetic studies and alternative strategies for studying the heterogeneity of alcohol dependence.     

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk.     

The impact of prenatal stress, fetal alcohol exposure, or both on development: perspectives from a primate model.

The question of whether psychosocial stress during pregnancy (alone or in combination with fetal alcohol exposure) has negative consequences for offspring has not been clearly established in human studies. In this article, we present an overview of three prospective longitudinal studies. Using rhesus monkeys as subjects, a noise or hormone stressor, alone or in combination with moderate level alcohol solution, was presented daily during different stages of pregnancy. Prenatal stress resulted in lighter birth weights in two of three studies, and males from the alcohol plus noise stress condition had reduced birth weights. There were no significant effects of any of the prenatal treatments on gestation duration. Both prenatal stress and moderate fetal alcohol exposure reduced attention span and neuromotor capabilities of offspring during the first month of life, while early gestation prenatal stress, during the period of neuronal migration, emerged as a period of enhanced vulnerability for these effects. Under conditions of challenge, prenatally stressed monkeys showed more disturbance behaviors and reduced locomotion and exploration as well as altered hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. Fetal alcohol exposed monkeys also showed increased HPA axis activity in response to stressful conditions. Finally, altered patterns of alcohol consumption during adolescence were associated with prenatal stress.     

Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence

Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability. Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3'-UTR of the CHRNA3 gene and nicotine dependence. In this study we performed a comprehensive association analysis of the CHRNA5-CHRNA3-CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence. Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence. These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation. Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.     

Genetic influences on brain growth restriction induced by development exposure to alcohol

Genetic factors have been implicated as contributing to the considerable variation in the severity of alcohol-related birth defects in offspring of women who drink heavily during pregnancy. Two animal models of alcohol-related developmental effects incorporated different behavior genetic approaches to examine genetic influences on brain and body growth following alcohol exposure during development. The first, extensively developed in Sprague-Dawley rats, examined the effects of three doses of alcohol administered to two inbred rat strains (MR and M520) via artificial-rearing procedures during the early postnatal brain growth spurt. In both strains, alcohol produced a dose-dependent restriction of brain weight (but not body weight) on postnatal day 10, compared to artificially reared controls. The MR strain was more susceptible to cerebellar growth restriction than the M520 strain, an effect not attributable to strain differences in blood alcohol concentrations. In the second model, pregnant female Long-sleep and Short-sleep mice, selectively bred for differences in initial sensitivity to the hypnotic effects of acute alcohol administration, were intubated with ethanol from gestational days 7-18. Controls included either sucrose or maltose/dextrin intubation controls and non-intubated controls. The LS offspring showed growth deficits and brain weight reductions in adulthood, while the SS offspring were resistant to these detrimental effects of the prenatal alcohol exposure. Thus, differences in either maternal or fetal genotype may contribute to individual differences in the severity of the effects of alcohol exposure during development.     

Adolescent Initiation of Drug Use: Effects of Prenatal Cocaine Exposure

ObjectiveTo investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use.MethodData are from a longitudinal study of PCE in which women and their offspring were assessed throughout childhood. Adolescents were interviewed at 15 years about their age at initiation of alcohol, marijuana, and tobacco. The sample consisted of 214 adolescents and their caregivers: 50% was of white ethnicity, and 50% African American.ResultsFirst trimester cocaine exposure significantly predicted earlier adolescent marijuana and alcohol initiation. The hazard of marijuana and alcohol initiation among exposed adolescents was almost two times greater than among nonexposed adolescents, adjusting for other significant factors. There were no differences in tobacco initiation. Other significant predictors of adolescent drug use were family history of alcohol problems, exposure to violence, and childhood maltreatment.ConclusionsCocaine exposure during early pregnancy was associated with initiation of marijuana and alcohol use. Exposure to violence, childhood maltreatment, and familial factors also predicted adolescent initiation, but did not mitigate the effects of PCE. The combination of these risk factors has significant implications for the development of later substance use, social, and psychiatric problems.     

How does maternal alcohol consumption during pregnancy affect the development of attention deficit/hyperactivity syndrome in the child

Besides genetic susceptibility, environmental factors and gene-environment interactions are of central interest in research on attention deficit/hyperactivity disorder in children. Focusing on maternal behaviour during pregnancy, prenatal maternal alcohol consumption is associated with behavioural disorders in children. In animal models, developmental disorders of brain structures as well as subsequent behavioural disorders - similar to findings in attention deficit disorder - were caused by prenatal alcohol exposure. These findings occur in small rodents (mice, rats) as well as in primates and can be caused by even moderate alcohol exposure. In foetal alcohol syndrome (FAS) and foetal alcohol spectrum disease (FASD) in humans, symptoms like hyperactivity, disruptive or impulsive behaviour along with reduced attention and slower reaction time are observed. These findings resemble the symptoms of ADHD. For that reason, children diagnosed with FAS/FASD are frequently diagnosed with ADHD in parallel. Even small amounts of alcohol during pregnancy are responsible for cognitive and behavioural impairments like a significantly decreased IQ. About 50?% of adult ADHD patients show alcohol abuse or dependency and/or other substance disorders. Due to this, a higher rate of prenatal exposition to psychoactive substances for children of mothers affected with ADHD seems probable. However, there are no sufficient data on ADHD and its association to substance abuse in pregnancy, which makes it difficult to quantify the impact of genetic and environmental causes for the development of childhood ADHD. So far, no link could be proven with a high level of evidence between moderate prenatal alcohol consumption and the development of childhood ADHD. It has to be recognised that all present studies are based on self-reported alcohol consumption. Data collected by this methodology are usually severely biased to an underestimation of alcohol abuse. Objective tests for alcohol abuse in pregnancy, such as the analysis of fatty acid ethyl esters or ethyl glucuronide in foetal feces after birth, show rates of alcohol consumption in pregnant women which are dramatically higher than reported. Therefore, studies investigating the association between prenatal alcohol exposure and ADHD should incorporate the analysis and validation of more objective methods, such as parameters for alcohol degradation.     

Association Between Parental Hospital-Treated Infection and the Risk of Schizophrenia in Adolescence and Early Adulthood

It has been suggested that infection during perinatal life may lie at the etiological root of schizophrenia. It has thus been hypothesized that the origin of schizophrenia may lie either in direct fetal infection and/or in a generally increased familial susceptibility to infections, some of which may occur during pregnancy. We explored these 2 hypotheses by assessing maternal infection during pregnancy and maternal as well as paternal infection in general as predictors of schizophrenia in their offspring. We found a slightly increased risk to be associated with prenatal infection exposure. However, the effect of prenatal infection exposure was not statistically significantly different from the effect of infection exposure in general. Parental infection appeared to be associated with development of schizophrenia in adolescence and early adulthood. Our study does not exclude a specific effect of infection during fetal life; yet, it does suggest that schizophrenia is associated with an increased familial liability to develop severe infection.     

Prenatal exposure to alcohol impairs social play behavior in adolescent male mice

Prenatal ethanol exposure affects brain development and causes neural impairment, leading to both cognitive and behavioral consequences in the offspring. Therefore, the aim of this study was to investigate the impact of prenatal exposure to small amounts of alcohol on social play behavior in adolescent male offspring. Swiss mice were prenatally exposed to ethanol by feeding pregnant dams with a liquid diet containing 25% alcohol-derived calories during gestation (alcohol group). They were then compared to both pair-fed dams that received an isocaloric liquid diet containing 0% alcohol-derived calories (pair-fed group) and dams with ad libitum access to a liquid control diet (control group). Additionally, maternal behavior was evaluated in terms of neural activation indexed via c-fos expression in the prefrontal cortex. Although dams exposed to alcohol during pregnancy did not alter their maternal behavior, the offspring presented a decrease in their social play behavior compared with both control and pair-fed offspring. The decrease in social play behavior may be associated with a decrease in number of c-fos-positive cells in the prefrontal cortex. The exposure to small amounts of alcohol during intrauterine development causes both a deficit in social play behavior and a reduction in the neuronal activity seen in the prefrontal cortex.     

Suicide attempts in an adolescent female twin sample.

OBJECTIVE: To examine suicide attempts in an epidemiologically and genetically informative youth sample. METHOD: 3,416 Missouri female adolescent twins (85% participation rate) were interviewed from 1995 to 2000 with a telephone version of the Child Semi-Structured Assessment for the Genetics of Alcoholism, which includes a detailed suicidal behavior section. Mean age was 15.5 years at assessment. RESULTS: At least one suicide attempt was reported by 4.2% of the subjects. First suicide attempts were all made before age 18 (and at a mean age of 13.6). Major depressive disorder, alcohol dependence, childhood physical abuse, social phobia, conduct disorder, and African-American ethnicity were the factors most associated with a suicide attempt history. Suicide attempt liability was familial, with genetic and shared environmental influences together accounting for 35% to 75% of the variance in risk. The twin/cotwin suicide attempt odds ratio was 5.6 (95% confidence interval [CI] 1.75-17.8) for monozygotic twins and 4.0 (95% CI 1.1 -14.7) for dizygotic twins after controlling for other psychiatric risk factors. CONCLUSIONS: In women, the predisposition to attempt suicide seems usually to manifest itself first during adolescence. The data show that youth suicide attempts are familial and possibly influenced by genetic factors, even when controlling for other psychopathology.