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PubMed2005

Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms.

BACKGROUND: Cigarette smoking rates in schizophrenia are higher than in the general population. OBJECTIVES: To determine whether cigarette smoking modifies cognitive deficits in schizophrenia and to establish the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related cognitive enhancement. DESIGN: Neuropsychological assessments were performed at smoking baseline, after overnight abstinence, and after smoking reinstatement across 3 separate test weeks during which subjects were pretreated in a counterbalanced manner with the nonselective nAChR antagonist mecamylamine hydrochloride (0, 5, or 10 mg/d). PARTICIPANTS: Twenty-five smokers with schizophrenia and 25 control smokers. SETTING: Outpatient mental health center. MAIN OUTCOME MEASURES: Visuospatial working memory (VSWM) and Continuous Performance Test (CPT) scores. RESULTS: In smokers with schizophrenia and control smokers, overnight abstinence led to undetectable plasma nicotine levels and an increase in tobacco craving. While abstinence reduced CPT hit rate in both groups, VSWM was only impaired in smokers with schizophrenia. Smoking reinstatement reversed abstinence-induced cognitive impairment. Enhancement of VSWM and CPT performance by smoking reinstatement in smokers with schizophrenia, but not the subjective effects of smoking, was blocked by mecamylamine treatment. CONCLUSIONS: Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.

Adult↗
PubMed2006

Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes.

BACKGROUND: Cocaine dependence is associated with high rates of relapse. Stress and drug cue exposure are known to increase cocaine craving and stress arousal, but the association between these responses and cocaine relapse has not been previously studied. OBJECTIVE: To examine whether stress-induced and drug cue-induced cocaine craving and hypothalamic-pituitary-adrenal axis responses evoked in the laboratory are associated with subsequent cocaine relapse. DESIGN: Prospective study design assessing cocaine relapse and drug use during a 90-day follow-up period after discharge from inpatient treatment and research. Data were analyzed by Cox proportional hazards regression and multiple regression. SETTING: Inpatient treatment and research unit in a community mental health center. PATIENTS: Forty-nine treatment-seeking cocaine-dependent individuals. MAIN OUTCOME MEASURES: Time to cocaine relapse, number of days of cocaine use, and amount of cocaine used per occasion in the follow-up phase. RESULTS: Greater stress-induced, but not drug cue-induced, cocaine craving was associated with a shorter time to cocaine relapse. Stress-induced corticotropin and cortisol responses predicted higher amounts of cocaine use per occasion in the 90-day follow-up. CONCLUSIONS: These results demonstrate that stress-related increases in cocaine craving and hypothalamic-pituitary-adrenal axis responses are each associated with specific cocaine relapse outcomes. The findings support the use of stress-induced drug craving and associated hypothalamic-pituitary-adrenal axis responses to evaluate cocaine relapse propensity. Furthermore, treatments that address stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses could be of benefit in improving relapse outcomes in cocaine dependence.

Adrenocorticotropic Hormone↗
PubMed2006

Acetaldehyde involvement in positive and negative alcohol expectancies in han Chinese persons with alcoholism.

CONTEXT: The ALDH2*2 allele has been shown to be a protective factor against alcoholism in a normal population owing in part to the elevated blood level of acetaldehyde and its accompanying physiological discomforts after drinking alcohol. Despite the well-established link between the ALDH2*2 allele and the physiological discomforts after drinking, very little is known regarding the psychological expectancies of drinking among persons with alcoholism with different ALDH genotypes. OBJECTIVES: To determine whether there are differences in craving, alcohol consumption, and alcohol outcome expectancies between persons with alcoholism who have the ALDH2*1/*2 genotype and persons with alcoholism who have the ALDH2*1/*1 genotype. DESIGN: Cross-sectional survey. SETTING: Six outpatient alcohol treatment facilities in Taiwan. PARTICIPANTS: Ninety-eight persons with alcoholism who met the DSM-IV criteria for current alcohol dependence. MAIN OUTCOME MEASURES: Alcohol Craving Scale, Form 90, and Alcohol Expectancies Scale scores. RESULTS: Overall, the ALDH2*1/*2 group had lower negative alcohol outcome expectancies (F(4,93) = 2.43, P < or = .05, eta(p)2 = 0.10). Specifically, they had fewer expected negative outcomes in the social or interpersonal domain (P < .05) and the emotional and physical domain (P < or = .005) than did the ALDH2*1/*1 group. Moreover, the ALDH2*1/*2 group had higher positive alcohol outcome expectancies (F(7,90) = 2.36, P < .05, eta(p)2 = 0.16), and they had more expected positive outcomes in the relaxation and tension reduction domain (P < .05). The 2 groups did not differ in alcohol craving (P = .61) or consumption (P = .11). CONCLUSIONS: Although the ALDH2*2 allele has been associated with negative physiological responses in normal samples in past research, the psychological expectancies of drinking are more positive and less negative for persons with alcoholism who have the ALDH2*1/*2 genotype. A role of acetaldehyde is implied in these effects, which seem to override the usual discomfort effects associated with protection against alcohol drinking. Future studies are needed to assess alcohol outcome expectancies at different phases of alcohol dependence and to evaluate the concurrent relationships of blood levels of acetaldehyde with physiological and psychological outcomes among persons with alcoholism who have different ALDH genotypes.

Acetaldehyde↗
PubMed1994

Co-morbidity of eating disorders and substance abuse review of the literature.

The comorbidity of eating disorders and substance use and abuse has frequently been reported in the past 15 years. To date, however, no synthesis of this literature exists. Here, 51 studies reporting on these associations are reviewed. Studies of substance use and abuse in eating disordered women are considered, as are studies of eating disorders among women classified as substance abusers. The rates of substance abuse among eating disordered women are also examined. This review indicates that associations are stronger with bulimia, and "bulimic" behaviors, than with anorexia nervosa. Analogously, bulimic anorectics report more substance use and abuse than restricters. The prevalence of drug abuse was not found to differ between the relatives of bulimics and anorectics. Several mechanisms explaining the eating disorder-substance use/abuse link are considered, and suggestions for future research made.

Adolescent↗
PubMed2001

An association study of DRD5 with smoking initiation and progression to nicotine dependence.

A large body of genetic epidemiological data strongly implicate genetic factors in the etiology of smoking behavior. Polymorphisms of genes in the dopaminergic system are plausible functional candidate genes and a linkage and an association study suggested that the type 5 dopamine receptor gene (DRD5) may be etiologically involved. We investigated the association of four DRD5 polymorphisms with smoking initiation and progression to nicotine dependence in a population-based sample of over 900 subjects. For smoking initiation, there was no significant association with the four DRD5 markers we studied; however, maximum likelihood analyses suggested the presence of a haplotype protective against smoking initiation. For progression to nicotine dependence, there were no strongly significant associations with the four DRD5 markers or for the estimated haplotypes. These data are not consistent with a strong etiological role for DRD5 in the etiology of these complex smoking behaviors.

Adolescent↗
PubMed2003

Cortisol as an indicator of dopaminergic effects on nicotine craving.

There is evidence that glucocorticoids mediate the activity of mesencephalic dopaminergic neurons which play an important role in drug-seeking behaviour and that the absence or presence of glucocorticoids determines the intensity of drug self-administration. Moreover, some experiments indicate that corticoids are increased after substance induced dopaminergic stimulation. These findings could imply (a) that differences in basal glucocorticoid levels are associated with differences in craving or (b) that dopamine (DA) induced corticoid release is an indicator of the sensitivity of the dopaminergic system. Therefore, in a sample of 36 male smokers whose DA system was challenged by a DA agonist (lisuride=LIS) and a DA antagonist (fluphenazine=FLU) in a balanced placebo controlled double-blind crossover design, it was investigated if (a) basal cortisol differences and (b) drug induced cortisol responses are related to the amount of nicotine craving after 3.5 h of deprivation from smoking. There were no differences in craving between subjects with high and low basal cortisol levels irrespective of the pharmacological treatment. However, the size of the cortisol change after the DA challenge and deprivation emerged as a good predictor for the amount of craving in that drug condition in which the cortisol response was most pronounced. Findings were interpreted as evidence for the role of cortisol as an indicator of DA sensitivity.

Adult↗
PubMed2001

Underlying cognitions in the selection of lottery tickets.

There is evidence that the faulty cognitions underlying an individual's playing behavior maintains and supports their gambling behavior. Sixty undergraduate students completed the South Oaks Gambling Screen (SOGS), a measure to assess pathological gambling, and a questionnaire ascertaining the type and frequency of their gambling activities. Sixteen Loto 6/49 tickets were presented to participants and ranked according to their perceived likelihood of being the winning ticket. The numbers on the tickets were categorized as: long sequences (e.g., 1-2-3-4-5-6), patterns and series in a pseudo-psychological order (e.g., 16-21-26-31-36-41), unbalanced (e.g., six numbers from 1-24 or 25-49), and those appearing to be random (e.g., 11-14-20-29-37-43). Verbal protocols of ticket selections were ranked into eight heuristics. Results revealed that for the entire sample the greatest percentage of tickets chosen for the first four selections were "random" tickets. Further, the most commonly cited reason for selecting and changing a lottery ticket was perceived randomness. The results are discussed with reference to the cognitions used when purchasing lottery tickets.

Adult↗
PubMed2006

Evidence for a hallucinogen dependence syndrome developing soon after onset of hallucinogen use during adolescence.

This study uses latent class methods and multiple regression to shed light on hypothesized hallucinogen dependence syndromes experienced by young people who have recently initiated hallucinogen use. It explores possible variation in risk. The study sample, identified within public-use data files of the 1999 National Household Survey on Drug Abuse (NHSDA), consists of 1186 recent-onset hallucinogen users, defined as having initiated hallucinogen use within 24 months of assessment (median elapsed time since onset of use -12 to 13 months). The recent-onset users in this sample were age 12 to 21 at the time of assessment and were between the ages of 10 and 21 at the time of their first hallucinogen use. The NHSDA included items to assess seven clinical features often associated with hallucinogen dependence, which were used in latent class modelling. Latent class analysis, in conjunction with prior theory, supports a three-class solution, with 2% of recent-onset users in a class that resembles a hallucinogen dependence syndrome, whereas 88% expressed few or no clinical features of dependence. The remaining 10% may reflect users who are at risk for dependence or in an early stage of dependence. Results from latent class regressions indicate that susceptibility to rapid transition from first hallucinogen use to onset of this hallucinogen dependence syndrome might be influenced by hallucinogenic compounds taken (for example, estimated relative risk, RR = 2.4, 95% CI = 1.6, 7.6 for users of MDMA versus users of LSD). Excess risk of rapid transition did not appear to depend upon age, sex, or race/ethnicity.

Adolescent↗
PubMed2007

Tobacco smoke particulate matter chemistry by NMR.

The submicron liquid droplets constituting the particulate matter of mainstream tobacco smoke (PMMTS) are viscous and of a composition that is complex and poorly understood. PMMTS is often approximately 80% w/w 'tar' where 'tar'=total PMMTS- (nicotine+water). Many of the chemical agents in MTS responsible for smoking-related cancers are found at least partially in the PMMTS portion of MTS. The properties of PMMTS vary with brand and with puffing patterns. The chemical forms and total levels of nicotine, the identities/levels of other compositionally dominant compounds, and the identities/levels of carcinogens are of interest. Most studies of the composition of PMMTS have involved extraction then chromatography. Such methods allow the determination of low-level constituents, but alter the samples such that direct information regarding chemical conditions within the PMMTS cannot be obtained. Here, we utilize nuclear magnetic resonance spectroscopy (NMR) to examine native PMMTS in conventional cigarettes, including measurements of the brand-dependent fraction of PMMTS nicotine that is in the free-base form (increasing this fraction in inhaled tobacco smoke affects the rates of the processes governing nicotine deposition in the respiratory tract, and so has implications for smoking behavior and addiction). We also demonstrate the use of NMR for characterizing the composition of PMMTS (including the levels of selected cigarette additives) when the cosolvent DMSO-d6 is added to improve spectral resolution. The native and solvent-assisted results open the door to a range of future studies.

Journal Article↗
PubMed2005

The course of life of survivors of childhood cancer.

The developmental consequences in adulthood of growing up with childhood cancer are not well understood. The Course of life questionnaire was developed to assess the attainment of developmental milestones retrospectively and socio-demographic outcomes in young adulthood. The aim of this study was to assess the course of life and socio-demographic outcomes in young adult survivors of childhood cancer. Knowledge about possible gaps in the course of life could enable health care providers to aim for the most favourable course of life. A total of 353 Dutch survivors and a comparison group of 508 peers without a history of cancer, all aged between 18 and 30, filled in the Course of life questionnaire. The course of life of the survivors was found to be hampered. The young adult survivors of childhood cancer in the Netherlands turned out to have achieved fewer milestones than their peers with respect to autonomy development, social development, and psycho-sexual development, or to have achieved the milestones when they were older than their peers. In addition, survivors displayed less risk behaviour than the comparison group. The survivors and the comparison group also differed on some socio-demographic issues. A considerably lower percentage of survivors than peers in the comparison group were married or living together, and/or employed. Their educational level, on the other hand, was as high as that of their peers.

Adolescent↗
PubMed2002

Brain DA D2 receptors predict reinforcing effects of stimulants in humans: replication study.

We had shown that striatal DA D2 receptors levels predicted the reinforcing responses to the psychostimulant drug methylphenidate in nondrug-abusing subjects. Here, we assessed the replicability of this finding. We measured D2 receptors with PET and [(11)C]raclopride (twice to determine stability) in seven nondrug-abusing subjects to assess if they predicted the self-reports of "drug-liking" to intravenous methylphenidate (0.5 mg/kg). DA D2 measures were significantly correlated with "drug-liking" in both evaluations (r = 0.82 and r = 0.78); subjects with the lowest levels reported the higher ratings of "drug-liking" and vice versa. These results replicate our previous findings and provide further evidence that striatal DA D2 receptors modulate reinforcing responses to stimulants in humans and may underlie predisposition for drug self-administration.

Adult↗
PubMedDate not supplied

Nicotine regulates smoking patterns.

BACKGROUND: Since 1953, the sales-weighted average "tar" and nicotine yields of commercial cigarettes in developed countries have significantly declined. However, the risk for chronic obstructive pulmonary disease (COPD) and for cancer of the lung has not decreased; adenocarcinoma incidence even continues to rise faster than the rate of squamous cell carcinoma of the lung. Undiminished risk of cigarette smokers for COPD and lung cancer is largely due to more intense smoking and deeper inhalation of the smoke of "low-yield" cigarettes and to significant changes in the smoke yields of certain lung carcinogens. METHODS: Puff frequency, puff duration, and puff volume of cigarette smokers were determined by a microcomputer-assisted flow transducer. These parameters were then programmed into a smoking machine to generate mainstream smoke for quantifying nicotine and lung carcinogens. RESULTS: Simulating the human smoking characteristics increases the yields of "tar" and nicotine per cigarette two- to threefold above Federal Trade Commission-reported levels. Smoke yields of lung carcinogens like benzo[alpha]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone parallel those of nicotine and "tar." CONCLUSIONS: The way people smoke and the total number of cigarettes consumed daily determine the uptake, i.e., the administered dose of nicotine, other toxic, and genotoxic smoke constituents. It is important to communicate this to consumers rather than letting the smokers believe that they are truly smoking a cigarette of lower smoke yields when they choose "light" or "ultralight" products.

Behavior, Addictive↗

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