High prevalence of alcohol use disorders in 454 young adult offspring from the San Diego prospective study.

Background: Preliminary evaluations of 212 drinking offspring from the San Diego Prospective Study (SDPD) indicated that over 50% developed alcohol use disorder (AUD) by their mid-20s. The present analysis evaluated if those findings remained robust when the group increased to 454 individuals, a sample size that facilitated a search for potential contributors to the high AUD prevalence.

Methods: Semistructured interviews were used to evaluate lifetime AUD diagnoses in 224 daughters and 230 sons from the SDPS (N = 454) by mean age 26.

Latent Trajectories of Persistence of Cannabis Use Across Four Decades in 329 Men From the San Diego Prospective Study.

Objective: These analyses use data from a 40-year prospective study to extend information into the sixth and seventh decades of life regarding latent trajectory classes of cannabis use and predictors of those classes.

Method: Data from the San Diego Prospective Study were analyzed for 329 men of European and Hispanic ethnicity who had used cannabis at about age 23 at study entry (Time 1) and who were interviewed about every 5 years through about age 60 to 70. Latent classes of cannabis use trajectories were evaluated using latent class growth analyses, baseline predictors of class membership were determined, and significant predictors of each class were established using logistic regression analyses.

Do personality characteristics predict future alcohol problems after considering current demography, substance use, and alcohol response?

Background: Several personality traits predict future alcohol problems but also relate to demographic and substance-related variables that themselves correlate with later adverse alcohol outcomes. Few prospective studies have evaluated whether personality measures predict alcohol problems after considering current demographic and substance-related variables.

Methods: Data from 414 drinkers without alcohol use disorder (AUD) from the Collaborative Study on the Genetics of Alcoholism (average age 20, 44% male) were followed over an average of 9 years.

Changes over time in endorsement of 11 DSM-IV alcohol use disorder (AUD) criteria in young adults with persistent or recurrent AUD in The Collaborative Study on the Genetics of Alcoholism.

Background: Endorsement of specific Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) alcohol use disorder (AUD) criteria have been shown to change significantly over time in men in their thirties who have persistent or recurrent AUD. However, few studies have documented whether the endorsement of AUD items changes over time in younger individuals or in women. We evaluated changes in the endorsement of AUD criteria in 377 men and women with persistent or recurrent AUD during their twenties.

Uncompetitive, adduct-forming SARM1 inhibitors are neuroprotective in preclinical models of nerve injury and disease.

Axon degeneration is an early pathological event in many neurological diseases. The identification of the nicotinamide adenine dinucleotide (NAD) hydrolase SARM1 as a central metabolic sensor and axon executioner presents an exciting opportunity to develop novel neuroprotective therapies that can prevent or halt the degenerative process, yet limited progress has been made on advancing efficacious inhibitors. We describe a class of NAD-dependent active-site SARM1 inhibitors that function by intercepting NAD hydrolysis and undergoing covalent conjugation with the reaction product adenosine diphosphate ribose (ADPR).

Structural and Mechanistic Regulation of the Pro-degenerative NAD Hydrolase SARM1.

The NADase SARM1 is a central switch in injury-activated axon degeneration, an early hallmark of many neurological diseases. Here, we present cryo-electron microscopy (cryo-EM) structures of autoinhibited (3.3 Å) and active SARM1 (6.

Impact of strain, sex, and estrous cycle on gamma butyrolactone-evoked absence seizures in rats.

Childhood absence epilepsy (CAE) is the most common pediatric epilepsy syndrome and is characterized by typical absence seizures (AS). AS are non-convulsive epileptic seizures characterized by a sudden loss of awareness and bilaterally generalized synchronous 2.5-4 Hz spike and slow-wave discharges (SWD).

A 22-Year Follow-Up (Range 16 to 23) of Original Subjects with Baseline Alcohol Use Disorders from the Collaborative Study on Genetics of Alcoholism.

Background: Recent reports indicate higher-than-expected problematic drinking in older populations. However, few data describe how to predict which older individuals are most likely to demonstrate alcohol-related problems, including those with earlier alcohol use disorders (AUDs). These analyses evaluate predictors of alcohol outcomes in individuals with earlier AUDs in the Collaborative Study on Genetics of Alcoholism (COGA).

Alcohol-related blackouts among college students: impact of low level of response to alcohol, ethnicity, sex, and environmental characteristics.

Objective: To explore how a genetically-influenced characteristic (the level of response to alcohol [LR]), ethnicity, and sex relate to environmental and attitudinal characteristics (peer drinking [PEER], drinking to cope [COPE], and alcohol expectancies [EXPECT]) regarding future alcohol-related blackouts (ARBs).

Methods: Structural equation models (SEMs) were used to evaluate how baseline variables related to ARB patterns in 462 college students over 55 weeks. Data were extracted from a longitudinal study of heavy drinking and its consequences at a U.

A Prospective Comparison of How the Level of Response to Alcohol and Impulsivity Relate to Future DSM-IV Alcohol Problems in the COGA Youth Panel.

Background: Alcohol problems reflect both environmental and genetic characteristics that often operate through endophenotypes like low levels of response (low LRs) to alcohol and higher impulsivity. Relationships of these preexisting characteristics to alcohol problems have been studied, but few analyses have included both low LR and impulsivity in the same model.

Methods: We extracted prospective data from 1,028 participants in the Prospective Youth Sample of the Collaborative Study on the Genetics of Alcoholism (COGA).

Predictors of Patterns of Alcohol-Related Blackouts Over Time in Youth From the Collaborative Study of the Genetics of Alcoholism: The Roles of Genetics and Cannabis.

Objective: Alcohol-related blackouts (ARBs) are anterograde amnesias related to heavy alcohol intake seen in about 50% of drinkers. Although a major determinant of ARBs relates to blood alcohol concentrations, additional contributions come from genetic vulnerabilities and possible impacts of cannabis use disorders (CUDs). We evaluated relationships of genetics and cannabis use to latent class trajectories of ARBs in 829 subjects from the Collaborative Study of the Genetics of Alcoholism (COGA).

Predictors of subgroups based on maximum drinks per occasion over six years for 833 adolescents and young adults in COGA.

Objective: A person's pattern of heavier drinking often changes over time, especially during the early drinking years, and reflects complex relationships among a wide range of characteristics. Optimal understanding of the predictors of drinking during times of change might come from studies of trajectories of alcohol intake rather than cross-sectional evaluations.

Method: The patterns of maximum drinks per occasion were evaluated every 2 years between the average ages of 18 and 24 years for 833 subjects from the Collaborative Study on the Genetics of Alcoholism.

A quasi-randomized group trial of a brief alcohol intervention on risky single occasion drinking among secondary school students.

Objectives: To show the effectiveness of a brief group alcohol intervention. Aims of the intervention were to reduce the frequency of heavy drinking occasions, maximum number of drinks on an occasion and overall weekly consumption.

Methods: A cluster quasi-randomized control trial (intervention n = 338; control n = 330) among 16- to 18-year-old secondary school students in the Swiss Canton of Zürich.

An evaluation of the full level of response to alcohol model of heavy drinking and problems in COGA offspring.

Objective: The low level of response (LR) to alcohol is an endophenotype related to heavier drinking and alcohol problems. Structural equation models (SEMs) indicate LR affects alcohol outcomes (ALCOUT) both directly and through mediation by drinking in peers (PEER), alcohol expectancies (EXPECT), and drinking to cope with stress (COPE), with some variation depending on the sample tested. This article presents the first full test of this LR-based model in young subjects from the Collaborative Study on the Genetics of Alcoholism (COGA).

The prognostic implications of DSM-IV abuse criteria in drinking adolescents.

Background: The validity of the DSM-IV diagnostic criteria for alcohol abuse has been questioned, and additional issues have been raised regarding the performance of this label in adolescents. While future diagnostic manuals might alter the approach to abuse, it is worthwhile to evaluate the implications of the current definition that has been in place since 1994.

Methods: Six hundred and sixteen 12-19-year-old subjects (mean 16.

Clinical implications of tolerance to alcohol in nondependent young drinkers.

Background: Ten percent of teenagers and young adults with no alcohol diagnosis and a third of those with alcohol abuse report tolerance to alcohol. However, relatively few data are available on the clinical implications of tolerance in nondependent men and women.

Methods: Data were gathered from 649 18-to-22-year-old drinking offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) families.

A comparison of factors associated with substance-induced versus independent depressions.

Objective: This article expands on the results from a 1997 report from the Collaborative Study on the Genetics of Alcoholism (COGA), using a new phase of the protocol to evaluate the prevalence and characteristics of substance-induced and independent major depressive episodes (MDEs) in a population of alcoholics and nonalcoholics.

Method: Data were evaluated from Phase II of the six-center-wide COGA investigation using information gathered beginning in January 1997. Data were generated through face-to-face evaluations using the updated version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II) interview, with distinctions between substanceinduced and independent MDEs based on the chronology of development of full depressive syndromes.

Externalizing disorders in the offspring from the San Diego prospective study of alcoholism.

Object: Conduct disorder (CD) and attention deficit hyperactivity disorder (ADHD) may be more prevalent in relatives of alcoholics and may predict alcohol and drug problems, but not all studies agree. This paper evaluates these questions in well-educated families of alcoholics and controls.

Methods: Data from 165, 14-25-year-old offspring in the San Diego Prospective Study were used to create Group 1 (n=17) with CD or ADHD and Group 2 (n=148) with no such diagnoses.

Patterns and correlates of drinking in offspring from the San Diego Prospective Study.

Background: The decision among young people to drink is complex and reflects multiple domains of influence. This paper applies the results from a previous test of an externalizing-based model predicting heavy drinking and alcohol problems in the probands from the San Diego Prospective Study to evaluate how similar characteristics relate to the decision to drink in their offspring.

Methods: Data were generated from multiple sources for 152 offspring with a mean age of 17.

The ability of the Self-Rating of the Effects of Alcohol (SRE) Scale to predict alcohol-related outcomes five years later.

Objective: A low level of response (LR) to alcohol as measured through alcohol challenges is an early-appearing, genetically influenced characteristic that predicts the risk of heavier drinking and alcohol problems. A less expensive and more easily used measure of LR, the retrospective Self-Rating of the Effects of Alcohol (SRE) questionnaire, also relates to alcohol intake and problems but has not been evaluated for its ability to predict alcohol-related problems 5 years later.

Method: At Time 1, 95 18- to 35-year-old (mean age: 25.

An evaluation of the performance of the self-rating of the effects of alcohol questionnaire in 12- and 35-year-old subjects.

Objective: A low level of response (LR) to alcohol was originally established through evidence of less alcohol-related change in several parameters at a given blood alcohol level. This is a genetically influenced phenotype associated with an increased risk for alcoholism. When measured by a retrospective questionnaire (the Self-Rating of the Effects of Alcohol [SRE] scale), a lower LR (here indicated by a report that more drinks were historically needed for various effects) correlates with a family history of alcoholism and numerous alcohol use-related variables.

Relationships among the level of response to alcohol and the number of alcoholic relatives in predicting alcohol-related outcomes.

Background: The low level of response (LR) to alcohol is related to a family history (FH) of alcohol use disorders (AUDs), and each predicts alcohol-related outcomes. Few studies have evaluated the interrelationships between the number of alcoholic relatives, LR, and a range of alcohol-related outcomes. This study tests the hypotheses that there will be an inverse relationship between LR and FH and that LR will be a better predictor of the maximum quantity of alcohol consumed.

Endocrine characteristics of late pregnant hyperketonaemic ewes and their reproductive performance following the induction of ovarian cyclicity out of the breeding season.

Ketosis was diagnosed in a flock of Merino ewes that conceived from synchronised oestrus in the early autumn period. On day 140 of pregnancy the ewes were sampled for determination of betaOH-butyrate (BHB), AST, glucose, non-esterified fatty acids (NEFA), total cholesterol (TCH), insulin, T4, T3, cortisol, IGF-1 and leptin. The results were evaluated according to the number of fetuses born some days later and the presence of hyperketonaemia (BHB: > or = 1.

Pregnancy stage and number of fetuses may influence maternal plasma leptin in ewes.

Maternal plasma leptin is elevated in ewes during pregnancy. The authors studied whether there was any relation between maternal plasma leptin and insulin concentrations, the number of fetuses and the circulating and faecal levels of gestagens. At the end of the breeding season in January the ovarian activity of Prolific Merino ewes was induced/synchronised with gestagen + eCG treatment.

A cross-generational comparison of alcohol challenges at about age 20 in 40 father-offspring pairs.

Background: A low level of response (LR) to alcohol is one of several genetically-influenced phenotypes associated with an elevated risk for heavy drinking and alcoholism. While most studies support the influence of genes for this characteristic, no data to date have addressed how LR established from alcohol challenges performs in similarly aged subjects across generations.

Methods: Between 1978 and 1988, 18-to-25-year-old non-alcohol-dependent Caucasian male drinkers participated in the San Diego Prospective Study alcohol challenges.