Biomedical subjects

S Kuperman

Publications and source records attributed to S Kuperman.

At least 19 recordsLinked to original sources

PubMed2006

Association of the kappa-opioid system with alcohol dependence.

Opioid receptors and their endogenous peptide ligands play important roles in the reward and reinforcement of drugs such as heroin, cocaine, and alcohol. The binding of dynorphins to the kappa-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the kappa-opioid receptor, and PDYN, which encodes its ligand prodynorphin, in a group of 1860 European American individuals from 219 multiplex alcohol dependent families. Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in the promoter and 3' end of PDYN, and in intron 2 of OPRK1. Haplotype analyses further supported the association of PDYN. Thus, variations in the genes encoding both the kappa-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the kappa-opioid system.

Alcoholism↗

PubMed2004

A genome-wide screen for genes influencing conduct disorder.

While behavioral genetic studies have suggested that childhood conduct disorder is under genetic influence, studies aimed at gene identification are lacking. This study represents the first genome-wide linkage analysis directed toward identifying genes contributing to conduct disorder. Genome screens of retrospectively reported childhood conduct disorder and conduct disorder symptomatology were carried out in the genetically informative adult sample collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). The results suggest that regions on chromosomes 19 and 2 may contain genes conferring risk to conduct disorder. Interestingly, the same region on chromosome 2 has also been linked to alcohol dependence in this sample. Childhood conduct disorder is known to be associated with the susceptibility for future alcohol problems. Taken together, these findings suggest that some of the genes contributing to alcohol dependence in adulthood may also contribute to conduct disorder in childhood.

Adult↗

PubMed2001

Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults.

Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18-60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.

Adrenergic Agents↗

PubMed2001

Risk domains associated with an adolescent alcohol dependence diagnosis.

AIMS: To determine the contribution of familial, interpersonal, academic and early substance use factors to relative risk for an alcohol dependence (AD) diagnosis in adolescents. METHODS: Information on 619 adolescents and their 390 sets of biological parents was obtained using the adolescent version of the Child Semi-Structured Assessment for the Genetics of Alcoholism (C-SSAGA) and the adult counterpart of this instrument, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). The C-SSAGA elicits a wide range of environmental, social, and psychiatric diagnostic information. Specific domain scale scores associated with an adolescent AD were computed, and generalized estimating equations (GEE) modeling was used to determine the odds ratio (relative risk) of the specified risk domains for an alcohol dependence diagnosis. FINDINGS: Risk factors for a DSM-III-R AD diagnosis included being at least 16 years of age, as well as negative parent-child interactions, school and personal-related difficulties (including the presence of an externalizing or internalizing DSM-III-R non-alcohol-related diagnosis), and early experimentations with a variety of substances. CONCLUSIONS: An array of familial, interpersonal, academic and early substance use factors were strongly associated with adolescent AD. Given the findings of this study, further research to determine temporal relationships that might influence the onset of adolescent alcohol dependence is warranted.

Adolescent↗

PubMed2001

A structured interview for medical school admission, Phase 1: initial procedures and results.

PURPOSE: Despite their widespread use, medical school admission interviews often are unstructured and lack reliability. This report describes the development of a structured admission interview designed to eliminate bias and provide valid information for selecting medical students, with preliminary information about the interview's reliability and validity. METHOD: After screening applications, 490 applicants to a public medical school residency program were interviewed by two faculty members using a structured interview format. Interview scores were compiled and correlated with undergraduate grade-point averages (GPAs); Medical College Admission Test (MCAT) scores; Iowa Evaluation Form (IEF) scores, an in-house evaluation of applicants' noncognitive abilities; and eventual admissions status. RESULTS: Interrater agreement was good; the percentages of rater pairs whose scores differed by one point or less ranged from 87% to 98%. Scores on the structured interview revealed low to moderate correlations with other admission criteria: 10 (p < 0.05) for cumulative GPA, 0.18 (p < 0.01) for MCAT Biological Science, 0.08 (p > 0.05) MCAT Physical Science, and 0.10 (p < 0.05) MCAT Verbal Reasoning. None of the correlations between the overall interview scores and the IEF scores reached statistical significance (p = 0.05). Higher overall scores on the structured interview did predict a greater likelihood of being accepted into the medical school and the interview score accounted for 20% of the incremental variance in admission status beyond GPA, MCAT, and IEF scores. CONCLUSIONS: The moderate-to-low correlations with other admission criteria suggest that the interview provided information about candidate credentials not obtained from other sources and accounted for a substantial proportion of the variance in admission status. This finding supports the considerable time and resources required to develop a structured interview for medical student admissions. Final judgment on the validity and utility of this interview should be made after follow-up performance data have been obtained and analyzed.

Educational Measurement↗

PubMed2001

Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence.

OBJECTIVE: The authors sought to clinically describe the relationship of disruptive behavior disorders with both alcohol dependence and the use of a variety of substances. METHOD: The Child Semi-Structured Assessment for the Genetics of Alcoholism was used to collect data on 54 adolescents with a diagnosis of alcohol dependence. The frequency and age at onset of the disruptive behavior disorder diagnoses were examined as well as age at first use of alcohol, tobacco, marijuana, and other street drugs. RESULTS: Nearly three-quarters of the alcohol-dependent adolescents had at least one disruptive behavior disorder diagnosis. Attention deficit hyperactivity disorder (ADHD) typically occurred first, followed by conduct disorder. Substance use began with alcohol or tobacco, followed by marijuana and then other street drugs. Alcohol dependence began significantly later than the onset of either ADHD or conduct disorder and significantly later than the first use of tobacco. CONCLUSIONS: Disruptive behavior diagnoses, particularly conduct disorder, typically precede the initiation of use of a variety of substances that, in turn, precede the diagnosis of alcohol dependence in adolescents.

Adolescent↗

PubMed2000

Genetics of event-related brain potentials in response to a semantic priming paradigm in families with a history of alcoholism.

Alcoholism↗

PubMed2000

Frontal P300 decrements, alcohol dependence, and antisocial personality disorder.

BACKGROUND: The purpose of this study was to examine the independent and interactive effects of alcohol dependence, antisocial personality disorder (ASPD), and age on brain function. METHODS: P300 event-related potentials (ERPs) were recorded from 393 alcohol-dependent and 170 non-alcohol-dependent adults while they performed a visual oddball task. The two subject groups were further subdivided based upon age and the presence/absence of ASPD. RESULTS: Alcohol dependence was associated with a significant P300 amplitude decrement at anterior electrode sites only. Antisocial personality disorder was also associated with reduced P300 amplitudes at anterior electrode sites; however, the effects were only significant among subjects 30 years of age or younger. To validate this association between ASPD and P300 amplitude a correlational analysis was performed; the correlation between anterior P300 amplitude and the total number of childhood conduct disorder and adult ASPD symptoms was significant. CONCLUSIONS: The P300 amplitude decrement found at anterior electrode sites among subjects with ASPD is consistent with the results of numerous ERP, neuroimaging, or neuropsychologic studies of anterior brain function. Our study is unique in suggesting that the effects of ASPD on anterior brain function are best detected during early adulthood. The study also suggests that the detrimental neurophysiologic effects of alcohol dependence predominantly involve the anterior brain.

Adolescent↗

PubMed2000

The P300 brain potential is reduced in smokers.

RATIONALE: Tobacco smoking is the most prevalent type of substance abuse, yet its biobehavioral etiology is little understood. Identification of differences between smokers and non-smokers on basic characteristics of neurocognitive functioning may help to elucidate the mechanisms of tobacco dependence. OBJECTIVES: This study assessed the relationship between smoking status and the P300 component of event-related potential (ERP) while controlling for potential confounders such as alcoholism, drug abuse, and psychopathology. METHODS: The ERP responses elicited by a visual oddball task were measured at the mid-parietal site in 905 current smokers, 463 ex-smokers, and 979 never smokers. RESULTS: P300 amplitude was significantly lower in current cigarette smokers compared to never-smokers. Ex-smokers did not differ significantly from never-smokers. P300 reduction was also associated with alcoholism, drug dependence, and family density of alcoholism. However, after controlling for smoking, only family density of alcoholism remained a significant predictor of P300 amplitude. CONCLUSIONS: The results indicate a significant effect of smoking status on P300 amplitude which is additive to family history of alcoholism and suggest that either (1) long-term tobacco smoking may produce a reversible change in brain function, or (2) reduced P300 may be a marker of risk for nicotine dependence.

Adolescent↗

PubMed1999

Heritability of event-related brain potentials in families with a history of alcoholism.

Event-related brain potentials (ERPs) are altered in patients with a variety of psychiatric disorders and may represent quantitative correlates of disease liability that are more amenable to genetic analysis than disease status itself. Estimates of heritability are presented for amplitude and latency of the N1 and P3 components of the ERP measured at 19 scalp locations in response to visual and auditory stimuli for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. Significant heritabilities were found for visual P3 amplitude in response to all stimuli and for visual P3 latency in response to target and novel, but not non-target, stimuli. Heritability of visual N1 latencies was uniformly low, whereas heritability of visual N1 amplitude was significant for all electrodes in response to the non-target stimuli but only for posterior electrodes in the other two stimulus conditions. Heritabilities for auditory target P3 were similar to those of the visual stimuli, with auditory target P3 amplitudes and latencies both demonstrating significant heritability. For auditory P2 in response to non-target stimuli, peak amplitude was heritable, but latency was not. Auditory N1 amplitude and latency were significantly heritable for both target and non-target conditions and did not demonstrate the anterior/posterior patterning obtained for visual N1 amplitude. This study represents the first systematic assessment of heritability of these potential neurophysiological markers in families with a history of alcoholism and suggests that many of these ERP phenotypes have heritabilities strong enough to justify genomic screening for loci jointly influencing ERP abnormalities and liability to alcoholism.

Adolescent↗

PubMed1999

Description of the Genetic Analysis Workshop 11 Collaborative Study on the Genetics of Alcoholism.

Problem 1 of Genetic Analysis Workshop 11 consists of data from a family study of the genetics of alcoholism and related traits contributed by the six centers making up the National Institute for Alcohol Abuse and Alcoholism sponsored by the Collaborative Study on the Genetics of Alcoholism (COGA). The family data included 1,214 members of 105 pedigrees ascertained for having three or more individuals affected with alcoholism. Data available to workshop participants included clinical phenotypes, personality measures, smoking behavior, event-related potentials, platelet monamine oxidase B activity, and a genome scan of 296 markers.

Alcoholism↗

PubMed1999

Evaluation of ADHD typology in three contrasting samples: a latent class approach.

OBJECTIVE: To identify subtypes of attention-deficit/hyperactivity disorder (ADHD) and characterize them as either categorical or continuous; to investigate familial resemblance for ADHD among sibling pairs; and to test the robustness of all results by using contrasting data sets. METHOD: Latent class analysis was applied to the ADHD symptom profiles obtained from parents or best informant about their offspring in 3 samples: a population-based set of female adolescent twins (724 monozygotic pairs, 594 dizygotic pairs) and male (N = 425) and female (N = 430) child and adolescent offspring ascertained from high-risk alcoholic families. RESULTS: Latent class analysis revealed 2 categories of clinically significant ADHD which were replicated in all 3 study groups: a subtype with high endorsements of ADHD inattention symptoms and a second combined type with high endorsements of both inattention and hyperactivity-impulsivity items. Both appeared to be continuous across all 3 data groups. The high-risk families contained a class in which members heavily endorsed the ADHD "fidget" item but not other ADHD items. A large proportion of the monozygotic sibs (80%) versus a smaller proportion of dizygotic sibs (52%) were assigned to the same latent class. Among the high-risk children and adolescents, 51% of the female and 41% of the male siblings were concordant for class membership. CONCLUSIONS: The pattern of latent classes suggested that ADHD consists of an inattentive and a combined subtype, within each of which lies a dimensional domain. These analyses further support that genetic factors are significant determinants of latent class membership.

Adolescent↗

PubMed1999

Relationship of child psychopathology to parental alcoholism and antisocial personality disorder.

OBJECTIVE: To evaluate the contributions of familial factors, including parental diagnoses of alcoholism and/or antisocial personality disorder (ASPD), to the risk of developing various child psychiatric diagnoses. METHOD: Four hundred sixty-three children and their biological parents were interviewed with adult and child versions of the Semi-Structured Assessment for the Genetics of Alcoholism. Demographic and psychiatric data were compared across 3 groups of children on the basis of the presence of parental alcoholism and ASPD (no other parental diagnoses were examined). Generalized estimating equations analyses allowed the inclusion of multiple children from each family in the analyses. RESULTS: Among offspring, parental alcoholism was associated with increased risks for attention-deficit hyperactivity disorder, conduct disorder (CD), and overanxious disorder. Parental alcoholism plus ASPD was associated with increased risk for oppositional defiant disorder. Dysfunctional parenting style was associated with increased risks for CD, alcohol abuse, and marijuana abuse. Low family socioeconomic status was associated with increased risk for CD. CONCLUSIONS: Parental diagnoses of alcoholism and ASPD were associated with increased risks for a variety of childhood psychiatric disorders, and dysfunctional parenting style was associated with the diagnoses of CD, alcohol abuse, and marijuana abuse.

Adolescent↗

PubMed1998

Quantitative trait loci analysis of human event-related brain potentials: P3 voltage.

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

Alcoholism↗

PubMed1998

Amplitude of visual P3 event-related potential as a phenotypic marker for a predisposition to alcoholism: preliminary results from the COGA Project. Collaborative Study on the Genetics of Alcoholism.

Recent data collected at six identical electrophysiological laboratories from the large national multisite Collaborative Study on the Genetics of Alcoholism provide evidence for considering the P3 amplitude of the event-related potential as a phenotypic marker for the risk of alcoholism. The distribution of P3 amplitude to target stimuli at the Pz electrode in individuals 16 years of age and over from 163 randomly ascertained control families (n = 687) was compared with those from 219 densely affected alcoholic families (n = 1276) in which three directly interviewed first-degree relatives met both DSM-III-R and Feighner criteria at the definite level for alcohol dependence (stage II). The control sample did not exclude individuals with psychiatric illness or alcoholism to obtain incidence rates of psychiatric disorders similar to those of the general population. P3 amplitude data from control families was converted to Z-scores, and a P3 amplitude beyond 2 SD's below the mean was considered an "abnormal trait." When age- and sex-matched distributions of P3 amplitude were compared, members of densely affected stage II families were more likely to manifest low P3 amplitudes (2 SD below the mean) than members of control families, comparing affected and unaffected offspring, and all individuals; all comparisons of these distributions between groups were significant (p < 0.00001). P3 amplitude means were also significantly lower in stage II family members, compared with control family members for all comparisons, namely probands, affected and unaffected individuals (p < 0.0001), and offspring (p < 0.01). Furthermore, affected individuals from stage II families, but not control families, had significantly lower P3 amplitudes than unaffected individuals (p < 0.001). Affected males from stage II families had significantly lower P3 amplitudes than affected females (p < 0.001). Recent linkage analyses indicate that visual P3 amplitude provides a biological phenotypic marker that has genetic underpinnings.

Adolescent↗

PubMed1997

P300 topography of amplitude/latency correlations.

The correlational association from 19 electrode sites between peak amplitude and latency for the P3(00) event-related brain potential (ERP) for n = 80 homogeneous subjects was assessed using a simple auditory discrimination task. The correlation strength varied systematically across scalp topography in different ways for the various ERP components. For the target stimuli, P3 amplitude and latency were negatively correlated and most tightly coupled over the frontal-central and right medial/lateral recording sites. In contrast, the N1 produced negative correlations that were strongest over the left and right central/lateral locations; P2 demonstrated a positive correlation that was strongest frontally and centrally; N2 demonstrated a positive correlations that was strongest over the central and parietal sites. ERPs from the standard stimuli produced generally similar patterns for the P3 and P2 components, with only weak or no reliable effects observed for the N1 and N2 potentials. Taken together, the findings suggest that analysis of amplitude/latency correlational relationships can provide information about ERP component generation. Theoretical implications are discussed.

Adult↗

PubMed1997

Slow brain potentials in a visual-spatial memory task: topographic distribution and inter-laboratory consistency.

Slow brain electrical potentials (SPs) were investigated in a visual-spatialmemory task. Two issues were addressed: (1) the nature and topographic distribution of the potentials obtained under such conditions; and (2) the consistency of the SPs when recorded in six identically configured laboratories. Fifteen young male subjects were studied at each laboratory (total n = 90). The paradigm entailed presentations of paired-visual patterns (S1 and S2), to which subjects responded with a choice reaction time response indicating whether or not the two patterns matched. A biphasic contingent negative variation (CNV) was produced which consisted of an early symmetric component with bilateral foci at posterior temporal sites and a subsequent mid-parietal dominant wave later in the retention interval. Although the CNVs from all laboratories were similar in waveform and in topographic distribution, there were significant inter-laboratory differences in amplitude of the slow potential components. The topographic distributions of the components and the possible role of sampling effects are discussed.

Adult↗

PubMed1996

Quantitative EEG differences in a nonclinical sample of children with ADHD and undifferentiated ADD.

OBJECTIVE: To use quantitative electroencephalographic (EEG) techniques to identify electrophysiological differences between children with distinct disorders of attention and/or hyperactivity. METHOD: Forty children from a prescreened community sample were evaluated by means of both spectral EEG and evoked response potential (ERP) techniques. The children were 7 to 13 years of age and were selected on the basis of membership in one of the following DSM-III-R categories: attention-deficit hyperactivity disorder (ADHD) (n = 16), undifferentiated attention deficit disorder (UADD) (n = 12), or no disruptive disorder diagnosis (n = 12). RESULTS: Spectral EEG revealed that UADD subjects had less delta band relative percent power (RPP) (p < .01), more beta band RPP (p < .01), and ERP findings of a decreased rare tone P300 amplitude (p < .02) compared with the control group. ADHD subjects had spectral EEG findings of increased beta band RPP (p < .05) and ERP findings of an increased common tone N100 latency (p < .02) and a decreased rare tone P300 amplitude (p < .02). Interhemispheric asymmetries appeared to distinguish the groups: the UADD group had spectral EEG asymmetries; the ADHD group had only ERP asymmetries; and the control group had no asymmetries. CONCLUSION: Quantitative EEG techniques may prove useful in differentiating specific subtypes of ADHD.

Adolescent↗