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Biomedical subjects

John Kramer

Publications and source records attributed to John Kramer.

18 recordsLinked to original sources
PubMed2026

Perceived partner substance use, genetic predispositions, and their associations with problematic alcohol use, emotional well-being, and relationship quality.

BACKGROUND: Romantic relationships are important contexts for substance use and emotional well-being. We tested the hypotheses that (i) genetic predispositions for alcohol consumption would be positively associated with partner substance use, (ii) partner substance use would moderate genetic influences on one's own alcohol outcomes, and (iii) partner discordance in substance use would be associated with lower emotional well-being and relationship quality. METHODS: Analyses included 2,357 participants (Mage = 51.4, 58.2% female) from the Collaborative Studies on the Genetics of Alcoholism. Focal measures included participants' reports of their own and their current partner's past-year substance use (frequencies of alcohol use, heavy drinking, drunkenness, cannabis use, and nicotine use), emotional well-being, and relationship quality. Participants' genetic predispositions were indexed with genome-wide polygenic scores for alcohol consumption (PGSAlc). Participant-partner substance use discordance was calculated as the difference between the participant's and their partner's use for each substance use measure, separately. RESULTS: Participant PGSAlc was not significantly associated with partners' perceived substance use. Frequent perceived partner alcohol use and heavy drinking significantly amplified the association between PGSAlc and alcohol use or drunkenness. Frequent perceived partner drunkenness and cannabis use significantly attenuated the association between PGSAlc and heavy drinking or frequency of alcohol use. Participant-partner discordance for several substance use measures was significantly associated with lower emotional well-being and relationship quality, controlling for participant and partner substance use main effects. CONCLUSIONS: The results highlight the importance of partner substance use in etiological models of alcohol use, emotional health outcomes, and relationship quality.

Humans↗
PubMed2006

Association of CHRM2 with IQ: converging evidence for a gene influencing intelligence.

The cholinergic neurotransmitter system is thought to be involved in many aspects of memory, attention, and higher cognition. In the Collaborative Study on the Genetics of Alcoholism (COGA) sample, we have previously reported linkage and association to the cholinergic muscarinic 2 receptor gene (CHRM2) on chromosome 7 with evoked EEG oscillations (Jones et al. 2004), providing evidence that this gene may be involved in human brain dynamics and cognition. In addition, a small number of genetic markers were genotyped in CHRM2 in the Minnesota Twin and Family Study (Comings et al. 2003) and a Dutch family study (Gosso et al. 2006, in press) and both research groups found evidence that this gene may be involved in intelligence. In the COGA sample, we have extensively genotyped SNPs within and flanking the CHRM2 gene. We find evidence of association with multiple SNPs across CHRM2 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R). These results remain significant after taking into account alcohol dependence and depression diagnoses in the sample.

Alcoholism↗
PubMed2006

The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages.

We use findings from the behavior genetics literature about how genetic factors (latently) influence alcohol dependence and related disorders to develop and test hypotheses about the risk associated with a specific gene, GABRA2, across different developmental stages. This gene has previously been associated with adult alcohol dependence in the Collaborative Study of the Genetics of Alcoholism (COGA) sample [Edenberg, H. J., Dick, D. M., Xuei, X., Tian, H., Almasy, L., Bauer, L. O., Crowe, R., Goate, A., Hesselbrock, V., Jones, K. A., Kwon, J., Li, T. K., Nurnberger Jr., J. I., O'Connor, S. J., Reich, T., Rice, J., Schuckit, M., Porjesz, B., Foroud, T., and Begleiter, H. (2004). Am. J. Hum. Genet. 74:705-714] and other studies [Covault, J., Gelernter, J., Hesselbrock, V., Nellissery, M., and Kranzler, H. R. (2004). Am. J. Med. Genet. B Neuropsychiatr. Genet. 129B:104-109; Lappalainen, J., Krupitsky, E., Remizov, M., Pchelina, S., Taraskina, A., Zvartau, E., Somberg, L. K., Covault, J., Kranzler, H. R., Krystal, J., and Gelernter, J. (2005). Alcohol. Clin. Exp. Res. 29:493-498]. In a sample of children and adolescents ascertained as part of the COGA project, we find that GABRA2 is significantly associated with childhood conduct disorder symptoms, but not with childhood alcohol dependence symptoms. A consistent elevation in risk for alcohol dependence associated with GABRA2 is not evident until the mid-20s and then remains throughout adulthood. GABRA2 is also associated with other drug dependence in our sample, both in adolescence and adulthood.

Adolescent↗
PubMed2006

Searching for the full picture: structural equation modeling in alcohol research.

This article summarizes the proceedings of a symposium presented at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California. This symposium begins with a description by Michael Windle of structural equation modeling (SEM), including the assets and liabilities of this approach. Next, Marc Schuckit and Tom Smith demonstrate the application of an SEM approach to understanding the impact of a low level of response to alcohol, using data from both adolescent and adult populations. Victor Hesselbrock and colleagues next review the results when an SEM approach is used in the longitudinal study of externalizing behaviors. This is followed by a description of the application of SEM to an affect-related model as discussed by John Kramer and Kathleen Bucholz. Finally, Kenneth Sher offers thoughts on how to place these findings into perspective.

Adaptation, Psychological↗
PubMed2006

Teenagers are right--parents do not know much: an analysis of adolescent-parent agreement on reports of adolescent substance use, abuse, and dependence.

BACKGROUND: Previous studies have shown that when assessing child psychopathology, parents tend to report more symptoms than children for externalizing disorders such as attention deficit hyperactivity disorder (ADHD), whereas children tend to report more symptoms for internalizing disorders such as major depression. Whether for clinical or research purposes, parents are also frequently asked to report on their children's experiences with alcohol and drugs. The purpose of this study was to analyze correspondence between adolescent and parent reports of adolescent substance use and abuse or dependence. METHODS: In the current study, 591 subjects 12 to 17 years old were interviewed using the child version of the Semi-Structured Assessment for the Genetics of Alcoholism (C-SSAGA) as part of the Collaborative Study on the Genetics of Alcoholism (COGA). One parent was also interviewed about each adolescent using the parent version of the C-SSAGA. Sensitivities, specificities, and kappa coefficients were calculated to assess parental agreement with adolescent reports of lifetime substance use and Diagnostic and Statistical Manual of Mental Disorders-Third Revision substance abuse or dependence. RESULTS: The results indicate that parents are somewhat knowledgeable about their children's use of substances, particularly those that are used most commonly. For example, 55% of adolescents who had smoked cigarettes, 50% who had used alcohol, and 47% who had used marijuana had a parent who knew that they used. However, parents were less aware of substance-related problems experienced by their offspring, agreeing with adolescent reports only 27% of the time for diagnoses of alcohol abuse or dependence and 26% of the time for diagnoses of marijuana abuse or dependence. Parent reports added few cases of substance use for 12- to 13 year-olds and essentially no cases for 16- to 17-year-olds. Parent reports added a nominal number of diagnoses of substance abuse or dependence for older adolescents. CONCLUSIONS: Whether for clinical or research purposes, the results emphasize the importance of directly assessing adolescents regarding alcohol and other substance use disorders. Furthermore, investigators should consider the specific disorder(s) being investigated and the ages of the children being studied when determining whether to include parent reports as part of study design.

Adolescent↗
PubMed2006

Precontemplated and impulsive suicide attempts among individuals with alcohol dependence.

OBJECTIVE: Alcohol dependence confers risk for suicidal behavior. Some suicide attempts are precontemplated, whereas other attempts are impulsive. The purpose of this study was to compare characteristics and correlates of impulsive and precontemplated suicide attempts. METHOD: Data were derived from analysis of The Collaborative Study on the Genetics of Alcoholism (COGA), which is a six-site family pedigree study of individuals in treatment for alcoholism (probands), relatives of probands, and control families. Subjects in the analysis were age 18 years or older with a diagnosis of current alcohol dependence according to the Diagnostic and Statistical Manual, Third Edition, Revised. Individuals reporting a lifetime history of one or more suicide attempts were divided into two strata: suicide attempters with a history of suicidal ideation that persisted for a week or more, conceptualized as attempters showing precontemplation (n=330), and suicide attempters without a history of persistent ideation, conceptualized as impulsive attempters (n=343). These groups were compared with subjects with no history of attempts (nonattempters; n=3115). RESULTS: Precontemplated acts were carried out with greater intent and were more likely to result in medical treatment. Dependence on illicit drugs and history of depression were more likely among attempters showing precontemplation. Impulsive attempts were more likely to be carried out by women and individuals with higher levels of alcohol-related aggression. CONCLUSIONS: Prevention of precontemplated suicide attempts by individuals with alcohol dependence should include a focus on recognition and treatment of depressive syndromes. Alcohol-related aggression was elevated among impulsive suicide attempters. Prevention efforts may include interventions targeting aggression.

Adolescent↗
PubMed2005

Linkage analyses of IQ in the collaborative study on the genetics of alcoholism (COGA) sample.

Intelligence, as measured by standardized psychological tests, has been shown to be highly heritable, though identifying specific genes influencing general intelligence has proven difficult. We conducted genome-wide linkage analyses to identify chromosomal regions containing genes influencing intelligence, as measured by WAIS full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ). Non-parametric multipoint linkage analyses were conducted with Merlin-regress software, using a sample of 1,111 genotyped and phenotyped individuals from 201 families, ascertained as part of the Collaborative Study on the Genetics of Alcoholism (COGA). The strongest evidence of linkage was obtained for FSIQ on chromosome 6 (LOD=3.28, 12 cM) near the marker D6S1006. This region was also implicated with suggestive linkage in a recently published genome screen of IQ in Australian and Dutch twin pairs, and it has been implicated in linkage studies of developmental dyslexia. Our findings provide further support that chromosome 6p contains gene(s) affecting intelligence.

Alcoholism↗
PubMed2005

Are there subgroups of bulimia nervosa based on comorbid psychiatric disorders?

OBJECTIVE: The current study sought to determine whether there are subtypes of bulimia nervosa (BN) differentiated by comorbid psychiatric disorders. METHOD: Data on comorbid psychiatric diagnoses in female relatives of probands and controls in the Collaborative Study of the Genetics of Alcoholism (COGA) who met criteria for BN (as outlined in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders) were analyzed using latent class analysis. Resulting latent classes were compared on a variety of variables related to impulsive behaviors and psychological functioning. RESULTS: The best-fitting solution, a two-class model, yielded one class (72%) characterized by substance dependence, depression, antisocial personality disorder (ASPD), and anxiety disorders, and another characterized by depression. The highly comorbid class had more suicidality, more daily smokers, sought help for emotional problems, and had lower Global Assessment of Functioning (GAF) scores compared with those in the comorbid depression only class. DISCUSSION: Latent class findings suggest the existence of two classes of BN differentiated by substance dependence, impulsive behaviors, and poorer psychological functioning.

Adult↗
PubMed2005

Prospective evaluation of the four DSM-IV criteria for alcohol abuse in a large population.

OBJECTIVE: In 1994 DSM-IV presented new criteria for substance abuse as repetitive problems in any one of four areas reflecting social, interpersonal, and legal difficulties. The authors systematically evaluate the performance of each of the four diagnostic criteria for alcohol abuse (problems in role functioning, alcohol use in hazardous situations, alcohol-related legal problems, and social or interpersonal problems) and determine the prognosis associated with a threshold of one versus two or more criterion endorsements. METHOD: Baseline and 5-year follow-up data were analyzed for 2,596 men and women from the Collaborative Study on the Genetics of Alcoholism, including 1,881 individuals with no alcohol-related diagnosis, and 715 with alcohol abuse, after excluding subjects with alcohol dependence. Performance of each criterion was analyzed for the entire group and for the 565 individuals who endorsed only one criterion at baseline. RESULTS: One alcohol abuse criterion was endorsed by 79% of subjects with alcohol abuse, 18.5% endorsed two, and 2.5% endorsed three. Compared with subjects who endorsed no criteria, individuals who reported any of the four diagnostic criteria at baseline had higher rates of alcohol and drug intake and related problems and higher rates of future difficulties. Diagnostic thresholds of one versus two abuse criteria at baseline performed equally well regarding most outcomes, although endorsement of two criteria predicted a higher risk for progression to dependence. The criterion most frequently endorsed--hazardous use--was associated with baseline substance use characteristics and problematic outcomes similar to those for the other criteria. CONCLUSIONS: The four DSM-IV alcohol abuse criteria performed well regarding both cross-sectional characteristics and the prediction of future problems, but no single diagnostic criterion was superior to any other. The similarity of outcomes for subjects with diagnostic thresholds of one versus two or more criteria may favor the continued use of a threshold of one criterion in the diagnosis of alcohol abuse.

Adult↗
PubMed2005

Evaluation of a level of response to alcohol-based structural equation model in adolescents.

OBJECTIVE: A low level of response (LR) to alcohol relates to a family history of alcoholism and predicts future heavier drinking and alcohol-related problems. The current analyses evaluate how LR functions within the context of a Social Information Processing Model, using 238 subjects aged 13 to 19 years from the Collaborative Study on the Genetics of Alcoholism (COGA). METHOD: A structural equation model (SEM) was used to evaluate the relationship among (1) a family history (FH) of alcoholism, (2) the LR to alcohol, (3) expectations as measured by the Alcohol Expectancy Questionnaire and (4) the recent pattern of drinking among parents in the home as predictors of the maximum recent quantity of drinking, the maximum number of drinks ever consumed in 24 hours and the number of alcohol problems in the teenage subjects. RESULTS: When tested in the SEM, LR functioned as a mediator of the relationship between an FH of alcoholism and alcoholic outcome, and expectancy functioned as a partial mediator of the relationship between LR and outcome. Invariance testing revealed that the SEM performed similarly in light and heavy drinkers, the two sexes, and older versus young subjects. Both the measurement model and SEM had good characteristics of fit, and direct paths within the model explained 49% of the variance of outcome. CONCLUSIONS: Consistent with results from the San Diego Prospective Study, when tested in the more heterogeneous COGA population, LR functioned as a mediator of the relationship between the FH and alcoholic outcome. In these adolescents, LR not only had a direct relationship to alcoholic outcome but, in contrast to prior results in adults, also appeared to operate through expectations of the effects of alcohol in predicting heavier drinking and a higher rate of alcohol-related problems among teenagers.

Adolescent↗
PubMed2004

The relationship between parental alcoholism and adolescent psychopathology: a systematic examination of parental comorbid psychopathology.

The relationship between parental alcohol dependence (with and without comorbid psychopathology) and adolescent psychopathology was examined in a sample of 665 13-17 year-old adolescents and their parents. Results indicated that adolescents who had parents diagnosed with alcohol dependence only did not significantly differ from adolescents who had parents with no psychopathology in regard to any of the measures of psychological symptomatology (substance use, conduct disorder, and depression) or clinical diagnoses (alcohol dependence, marijuana dependence, conduct disorder, or depression) assessed. In contrast, adolescents who had parents diagnosed with alcohol dependence and either comorbid drug dependence or depression were more likely to exhibit higher levels of psychological symptomatology. In addition, adolescents who had parents diagnosed with alcohol dependence, depression, and drug dependence were most likely to exhibit psychological problems. These findings underscore the importance of considering parental comorbid psychopathology when examining the relationship between parental alcoholism and offspring adjustment.

Adolescent↗
PubMed2004

The search for genetic risk factors associated with suicidal behavior.

BACKGROUND: Suicide and suicidal behavior are prevalent among individuals with psychiatric disorders, including alcohol dependence. A genome screen was performed in multiplex alcohol dependent families ascertained as part of the Collaborative Study on the Genetics of Alcoholism to identify chromosomal regions of interest related to two types of suicidal behavior: suicide attempts and suicidality. METHODS: Sibling pair analyses were used to conduct linkage analyses using both qualitative and quantitative suicide-related phenotypes. The qualitative trait of "suicide attempts" was examined using 59 affected sibling pairs. The quantitative trait of "suicidality" was examined using all possible 1366 sibling pairs and 705 independent sibling pairs. RESULTS: For the qualitative phenotype suicide attempts, chromosome 2 yielded a maximum lod score of 4.2. For the quantitative suicidality index, a maximum lod score of 1.8 was observed on chromosome 3, and a lod score of 1.5 was found on chromosome 1. CONCLUSIONS: This study represents the first genome-wide scan of suicidal behavior. Significant evidence of linkage was found on chromosome 2 for the phenotype suicide attempts, the same chromosomal region previously reported to be linked to alcohol dependence in this sample. This finding does not seem to be due solely to an association between suicide and alcohol dependence. There was more modest evidence of linkage to chromosomes 1 and 3 for suicidality; however, these findings did not reach statistical significance. There was no overlap in findings for these two phenotypes of suicidal behavior.

Alcoholism↗
PubMed2004

Parental substance use consequences and adolescent psychopathology.

OBJECTIVE: This study examines the relationship between parental substance use consequences and adolescent psychological problems by gender of the adolescent and gender of the parent. METHOD: The data in this study were collected between 1989 and 1994 from 173 (116 proband and 57 control) families participating in the Collaborative Study on the Genetics of Alcoholism (COGA) project. All 173 adolescents (89 [51%] boys) completed the Structured Assessment Record of Alcoholic Homes (SARAH) to assess parental substance use consequences. In addition, the Semi-Structured Assessment for the Genetics of Alcoholism for Adolescents (C-SSAGA-A) was administered to all adolescents to obtain clinical psychiatric diagnoses. RESULTS: Concern about mother's substance use was significantly associated with adolescent alcohol dependence and major depressive disorder. In addition, concern about father's substance use was significantly related to adolescent alcohol dependence. Avoidance of mother when she was drinking or using drugs and maternal anger when drinking or using drugs also was significantly associated with adolescent alcohol dependence, conduct disorder and major depressive disorder. In contrast, avoidance of father and paternal anger when drinking or using drugs was not related to any of the adolescent diagnoses. CONCLUSIONS: These results suggest that maternal substance use consequences may be more closely linked to adolescent psychological adjustment than are paternal substance use consequences.

Adolescent↗
PubMed2002

The prevalence and clinical course of sedative-hypnotic abuse and dependence in a large cohort.

Relatively little is known about the prevalence and clinical characteristics of dependence on sedative-hypnotics, and almost nothing has been published regarding abuse. This report relates information on Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IIIR) sedative-hypnotic use disorders among subjects from the Collaborative Study on the Genetics of Alcoholism (COGA). A standardized interview was used to generate data on 407 men and women in Group 1 with sedative-hypnotic dependence (4.4% of the COGA sample), 34 in Group 2 with abuse (0.4%), and 3,426 comparison subjects in Group 3 with alcohol dependence in the absence of a sedative-hypnotic use disorder (36.7%). The remaining COGA subjects (48.5%) were not included as they had neither alcohol nor sedative-hypnotic dependence or abuse. Those with sedative-hypnotic abuse or dependence were more likely to be Caucasian individuals with abuse or dependence on marijuana, cocaine, amphetamines, or opioids. Subjects in Groups 1 and 2 were also more likely to have histories of independent major depressive and panic disorders, as well as substance-induced mood disorders. Those with dependence, compared to abuse, were likely to be women, reported staying intoxicated for a day or more, but noted less abuse of opioids or amphetamines, although Group 2 members also had high rates of difficulties with sedative-hypnotics. These results highlight notable rates of sedative-hypnotic dependence in the COGA families, and indicate that while sedative-hypnotic abuse does occur, and while the clinical course can involve relatively serious problems, it is less common than dependence.

Adult↗
PubMed2002

Suggestive linkage on chromosome 1 for a quantitative alcohol-related phenotype.

BACKGROUND: Alcohol dependence is a clinically and etiologically heterogeneous disorder. Accordingly, a variety of subtypes of alcohol-dependent individuals have been proposed, and multiple operational definitions of alcohol use, abuse, and dependence have been used in linkage analyses directed toward detecting genes involved in alcohol use and problems. Here, we develop quantitative phenotypes that characterize drinking patterns among both alcoholic and nonalcoholic subjects, and use these phenotypes in subsequent linkage analyses. METHODS: More than 9000 individuals from alcoholic and control families were administered a semistructured interview and personality questionnaire as part of the initial stage of the Collaborative Study on the Genetics of Alcoholism (COGA). A principal component analysis was conducted on items that captured many of the dimensions of drinking and related behaviors, including aspects of alcohol use, antisocial behavior and affective disturbance when drinking, and personality. Factor scores were computed for all individuals. Nonparametric linkage analyses were conducted on these factor scores, in the initial COGA sample consisting of 987 individuals from 105 extended families, and in a replication sample consisting of 1295 individuals from 157 extended families. RESULTS: Three factors were identified, accounting for 68% of the total variance. The most promising regions of linkage appeared for factor 2, on which higher scores indicate a later age of onset of regular drinking and higher harm avoidance. Chromosome 1 yielded consistent evidence of linkage in both samples, with a maximum lod score of 3.3 when the samples were combined for analysis. Consistent suggestion of linkage also was found to chromosome 15. CONCLUSIONS: Developing novel phenotypes that more accurately model the effect of influential genes may help efforts to detect genes involved in complex disorders. Applying principal component analysis in the COGA sample provided support for some regions of linkage previously reported in COGA, and identified other new, promising regions of linkage.

Alcoholism↗
PubMed1993

Large granular lymphocyte leukemia in a horse.

Large granular lymphocytes (LGL) occur as a leukemic or aleukemic neoplasia in humans,(1) rats,(2) cats,(3,4) dogs,(5) and horses.(6) The single case of equine LGL previously reported was aleukemic.(5) In contrast to this previous report of aleukemic equine LGL neoplasia, the leukemia in the case presented here established the antemortem diagnosis of LGL.

Journal Article↗