Biomedical subjects

K G Lynch

Publications and source records attributed to K G Lynch.

15 recordsLinked to original sources

PubMed2006

Association of OPRM1 A118G variant with the relative reinforcing value of nicotine.

RATIONALE: The endogenous opioid system has been implicated in substance abuse and response to pharmacotherapies for nicotine and alcohol addiction. We examined (1) the association of the functional OPRM1 A118G variant with the relative reinforcing value of nicotine and (2) the main and interacting effects of the mu-opioid receptor antagonist naltrexone on nicotine reinforcement. METHODS: In a within-subject, double-blind human laboratory study, 30 smokers of each OPRM1 genotype (A/A vs. A/G or G/G) participated in two experimental sessions following 4 days of orally administered naltrexone 50 mg or placebo. Participants completed a validated assessment of the relative reinforcing value of nicotine. This cigarette choice paradigm assesses self-administration of 0.6 mg nicotine vs. 0.05 mg (denicotinized) cigarettes after a brief period of nicotine abstinence. RESULTS: The relative reinforcing value of nicotine (number of nicotine cigarette puffs) was predicted by a significant OPRM1 by gender interaction. Among women, the low-activity G allele (A/G and G/G) was associated with a reduced reinforcing value of nicotine; among male smokers, there was no association with genotype. Smokers carrying a G allele were also significantly less likely to differentiate the nicotine vs. denicotinized cigarettes by subjective ratings of satisfaction and strength. No evidence for an effect of naltrexone on nicotine reinforcement was found in the overall sample or in the genotype or gender subgroups. CONCLUSIONS: This study provides initial evidence for an association of the OPRM1 A118G variant with nicotine reinforcement in women.

Adaptation, Psychological↗

PubMed2004

Power analyses for longitudinal trials and other clustered designs.

Existing methods for power and sample size estimation for longitudinal and other clustered study designs have limited applications. In this paper, we review and extend existing approaches to improve these limitations. In particular, we focus on power analysis for the two most popular approaches for clustered data analysis, the generalized estimating equations and the linear mixed-effects models. By basing the derivation of the power function on the asymptotic distribution of the model estimates, the proposed approach provides estimates of power that are consistent with the methods of inference for data analysis. The proposed methodology is illustrated with numerous examples that are motivated by real study designs.

Clinical Trials as Topic↗

PubMed2001

Comorbid disruptive behavior disorder symptoms and their relationship to adolescent alcohol use disorders.

This investigation evaluated the relationship between comorbid Disruptive Behavior Disorder (DBD) and Alcohol Use Disorder (AUD) symptoms in adolescents. The factor structure of both DBD and AUD symptoms was evaluated and a structural model then examined the relationships between comorbid DBD symptoms and AUD symptoms. A full model and a sex differentiated model were evaluated. For the full model, only Conduct Disorder (CD) symptoms were associated with AUD symptoms. In the sex differentiated model, male adolescents demonstrated direct effects of CD and Attention Deficit Hyperactivity Disorder (ADHD) on AUD. For female adolescents we found only a robust direct effect of CD on AUD. We concluded that CD symptoms have the strongest concurrent association with AUD symptoms in adolescents. However, there is preliminary evidence of sex heterogeneity.

Adolescent↗

PubMed2001

Course of functioning in adolescents 1 year after alcohol and other drug treatment.

Clinical course was studied in 131 male and female adolescents with current alcohol use disorder (AUD) at baseline (BL). Participants were classified into 4 groups according to their diagnosis and drinking pattern 1 year later. The 4 groups were compared with each other and with 37 community control participants. Results showed that over half of the clinical sample no longer had a current AUD at 1 year; about 64% were and 36% were not still drinking. BL discriminators of 1-year status were alcohol dependence, other drug use, and coping. All of the clinical groups tended to show improvement at 1 year in the main dependent variables, and the abstainers' level of drug use and coping were comparable with that of the community participants. These findings suggest that many adolescents improve in functioning during the 1 year after alcohol and drug treatment and that a stress and coping model is useful for studying clinical course of AUDs in adolescents.

Adaptation, Psychological↗

PubMed2001

Alcohol use disorders and risk factor interactions for adolescent suicidal ideation and attempts.

Four hundred eighty-two adolescents who were diagnosed with at least one mental disorder were studied to determine the predictors of suicidal ideation and suicide attempts. Major depression was predictive of suicidal ideation and suicide attempts for both genders. Chronic stress was found predictive of male suicidal ideation, while low self-esteem and high family dysfunction were found to be predictive of suicidal ideation in females. Statistical trends suggest that females with comorbid alcohol use/conduct disorder were approximately three times more likely to have attempted suicide than those with only one of these conditions. Clinicians working with adolescents should be aware that, while depression remains the number one clinical risk forsuicidal behavior, risk factors for suicidal ideation may be different than those for attempted suicide and may vary by gender.

Adolescent↗

PubMed2001

Constructive thinking in adolescents with substance use disorders.

This study examined the concurrent validity and clinical correlates of the Constructive Thinking Inventory (CTI), a measure of experiential coping, in 551 adolescents aged 14-18 years with and without Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) substance use disorders (SUDs). The CTI was correlated with depression, anxiety, and conduct problems. After controlling for demographics and comorbid lifetime psychiatric disorders, the CTI scales of Behavioral Coping and Categorical Thinking distinguished adolescents with and without SUDs. Implications of these findings for assessment and treatment are discussed.

Adaptation, Psychological↗

PubMed2001

Health problems in adolescents with alcohol use disorders: self-report, liver injury, and physical examination findings and correlates.

BACKGROUND: Although adolescent alcohol consumption has been found to be positively correlated with self-reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self-reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated. METHODS: The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or alcohol abuse (n = 57) and reference adolescents without AUDs recruited from community sources (n = 131). The assessment of health status included self-reported health problems in 15 areas; serum liver enzyme assays, including gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire. RESULTS: Adolescent AUDs were associated with more self-reported health problems, higher gamma-glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self-reported health problems, mediated the relationship between AUDs and self-reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities. CONCLUSIONS: These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self-reported health problems were probably best understood, in this context, as a negative emotionality manifestation.

Adolescent↗

PubMed2000

Inter-rater reliability of the SCID alcohol and substance use disorders section among adolescents.

Diagnostic interviews for substance use disorders tend to have high reliability among adults. We examined the inter-rater reliability of the substance use disorders section of the Structured Clinical Interview for the DSM, using 46 male and 25 female adolescent drinkers recruited from community and treatment sources. Inter-rater reliability was high for individual DSM-IV alcohol symptoms (kappa=0.84-1.0) and diagnoses (kappa=0.94), and for other substance use disorder diagnoses (kappa=0.82-1.0).

Adolescent↗

PubMed2000

Gender differences and similarities in the personality correlates of adolescent alcohol problems.

The personality traits of behavioral under-control (BU) and negative emotionality (NE) are associated with alcohol problems. The authors examined gender differences in the associations of BU and NE with alcohol problems in 710 adolescents recruited from community and treatment sources. Multiple measures were used to characterize each construct, and the specified 2-factor model provided a reasonably good fit to the data. ANCOVAs were used to examine each construct by gender across four groups: never-regular drinkers, regular drinkers, and those with DSM-IV alcohol abuse and alcohol dependence. Males had significantly higher BU and lower NE than did females. BU and NE both increased with degree of alcohol problems. However, there was not a significant Gender x Alcohol Group interaction for BU or NE. Although there are gender differences in levels of BU and NE, mechanisms of alcohol involvement related to these 2 personality traits may operate similarly in adolescent males and females.

Adolescent↗

PubMed2000

Characteristics of suicide attempts of patients with major depressive episode and borderline personality disorder: a comparative study.

OBJECTIVE: Suicidal behavior is highly prevalent in borderline personality disorder and major depressive episode, although the characteristics of suicide attempts in the two disorders are believed to differ. Comorbidity of borderline personality disorder and major depressive episode may obscure characteristics of suicide attempts that are uniquely related to the psychopathology of each disorder. We compared suicidal behavior in patients with borderline personality disorder, major depressive episode, and borderline personality disorder plus major depressive episode to determine whether characteristics of suicide attempts differed between groups and if aspects of core psychopathology predicted specific attempt characteristics. METHOD: Eighty-one inpatients with borderline personality disorder, including 49 patients with borderline personality disorder plus major depressive episode, were compared to 77 inpatients with major depressive episode alone on measures of depressed mood, hopelessness, impulsive aggression, and suicidal behavior, including lifetime number of attempts, degree of lethal intent, objective planning, medical damage, and degree of violence of suicide methods. RESULTS: No significant differences were found in the characteristics of suicide attempts between patients with borderline personality disorder and those with major depressive episode. However, patients with both disorders had the greatest number of suicide attempts and the highest level of objective planning. An increase in either impulsive aggression or hopelessness or a diagnosis of borderline personality disorder predicted a greater number of attempts. Hopelessness predicted lethal intent in all three groups and predicted objective planning in the group with both disorders. Medical damage resulting from the most serious lifetime suicide attempt was predicted by number of attempts. CONCLUSIONS: Comorbidity of borderline personality disorder with major depressive episode increases the number and seriousness of suicide attempts. Hopelessness and impulsive aggression independently increase the risk of suicidal behavior in patients with borderline personality disorder and in patients with major depressive episode.

Adolescent↗

PubMed2000

Recent life events, social adjustment, and suicide attempts in patients with major depression and borderline personality disorder.

This study investigated the impact of recent life events and social adjustment on suicide attempter status in 34 patients with major depression, 24 patients with borderline personality disorder, and 22 patients with co-morbid major depression and borderline personality disorder. Suicide attempters reported more recent life events and scored lower on a measure of social adjustment in their families and overall social adjustment, compared with non-attempters. Borderline disordered and borderline or depressed patients were more likely to have attempted suicide than patients with major depression only. Recent life events did not predict attempter status. Lower social adjustment in the immediate family and lower overall social adjustment were predictive of suicide attempter classification, regardless of diagnosis. Borderline disordered patients low on overall social adjustment were over 16 times more likely to have attempted suicide than patients diagnosed with major depression only. Recent life events may elevate suicide risk in groups already at high risk for suicide completion, whereas high levels of social adjustment may be protective against stress-related suicidal behavior.

Adult↗

PubMed2000

Serotonin, impulsivity, and alcohol use disorders in the older adolescent: a psychobiological study.

BACKGROUND: Alcohol use disorders (AUDs) among adolescents are associated with a high prevalence of conduct disorder (CD), much as type II alcoholism in adults is associated with impulsive-aggressive behavior and antisocial personality traits. Adults with impulsive personality disorders and AUD demonstrate diminished central serotonergic responsiveness to serotonergic agonists. Dysregulation of central serotonergic function may contribute to a vulnerability to impulsive-aggressive behavior, CD, and AUD. We studied older adolescents, both male and female, to examine the relationships between sex, dispositional impulsivity, aggressivity, CD, and responsiveness to serotonergic challenge with d,l fenfluramine (FEN) early in the development of AUD. METHODS: Thirty-six adolescents between the ages of 16 and 21 years were assessed for DSM-IV AUD and other Axis I disorders by using the Psychoactive Substance Use Disorders section of the Structured Clinical Interview for DSM III-R, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, and CD interviews. Impulsivity and aggressivity were assessed by the Barratt Impulsiveness Scale, Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Eysenck Impulsiveness Questionnaire, Youth Self Report, and Multidimensional Personality Questionnaires. FEN was administered as 0.8 mg/kg to a maximum of 60 mg, and blood was sampled at fixed intervals for prolactin, cortisol, fenfluramine, and norfenfluramine levels. RESULTS: Eighteen adolescents (12 male, 6 female) with AUD scored significantly higher on all measures of impulsivity and aggressivity compared with 18 healthy controls (12 male, 6 female). There were no significant differences between groups in peak prolactin or cortisol responses (minus baseline), or area-under-the-curve determinations (AUC); however, 9 subjects with AUD and comorbid CD had significantly elevated cortisol AUC levels compared with subjects with AUD and no CD or with normal controls. In the total sample, cortisol AUC was associated positively with measures of aggression. CONCLUSIONS: Adolescents with early-onset AUD are characterized by impulsivity and aggressivity compared with healthy peers but do not demonstrate the diminished prolactin or cortisol responses to FEN characteristic of adult alcoholics with impulsive-aggression.

Adolescent↗

PubMed2000

Reliability and concurrent validity of DSM-IV subclinical symptom ratings for alcohol use disorders among adolescents.

BACKGROUND: The concurrent validity of subclinical ratings for psychiatric symptoms can help refine symptom definitions and threshold criteria. However, virtually no research has examined subclinical ratings for DSM-IV symptoms in psychiatric diagnostic interviews. This study examined the frequency, reliability, and concurrent validity of subclinical ratings for 11 symptoms of alcohol use disorders among adolescents. METHODS: Subjects were 239 male and 164 female adolescents ages 14 to 18 recruited from treatment and community sources. Symptoms and diagnoses were made with an adapted version of the Structured Clinical Interview for the DSM-IV. RESULTS: Subclinical ratings showed acceptable to high interrater reliability. The proportion of subclinical ratings tended to decrease with increasing levels of alcohol problems. For 10 of the 11 symptoms, subjects with subclinical ratings were distinguished from those with absent and/or those with present ratings. Subjects with subclinical ratings were often distinct from those with present ratings but less often distinct from those with absent ratings. CONCLUSIONS: For most of the DSM-IV alcohol use disorder symptoms, subclinical ratings appear to be reliable and valid and provide information beyond dichotomous symptom classifications for adolescents. Threshold criteria appear to be appropriate in many cases, but boundaries between absent and subclinical ratings are "fuzzy." Practical and research implications are discussed.

Adolescent↗

PubMed1999

Risky sexual behaviors among adolescents with alcohol use disorders.

Little is known about risky sexual activity among adolescents with alcohol use disorders. This study of 371 adolescent drinkers found that those with alcohol disorders were more likely than other drinkers to be sexually active, to have greater numbers of partners, and to initiate sexual activity at slightly younger ages. Independent of alcohol group, females were more likely than males to have unprotected sexual encounters.

Adolescent↗

PubMed1999

Psychopathology and substance-related problems during early adolescence: a survival analysis.

Examined the chronological and statistical relations among onsets of psychopathology, alcohol and cannabis use, and substance-related problem psychopathology, alcohol and cannabis use, and substance-related problems from late childhood through early adolescence in boys of fathers with substance use disorder (SUD; high average risk: n = 177) and without SUD (low average risk: n = 203) using survival analysis. Proportional hazard models indicated that antisocial disorders were predicted by risk group and mediated the observed relation between risk group and substance-related problems. Negative affect disorders were predicted by risk group but did not predict substance involvement in early adolescence. Results support a model in which paternal SUD predisposes to increased antisocial and negative affect disorders in boys, and antisocial disorders lead to substance-related problems in early adolescence.

Adolescent↗