Impact of persistent substance misuse on 1-year outcome in first-episode psychosis.

BACKGROUND: Substance misuse is a common comorbid problem in people presenting with first-episode psychosis and is associated with a poor short-term outcome. AIMS: The aim of this study is to examine differences in baseline characteristics and 1-year outcome between individuals with first-episode psychosis who have never misused substances, those who stop misusing substances after initial presentation and those who persistently misuse substances over the 1-year assessment period. METHOD: Patients were recruited to the Northern Ireland First Episode Psychosis Study (n = 272). Clinical assessments were performed at baseline and at 1 year (n = 194) and data were collected from the case notes. RESULTS: Individuals with persistent substance misuse had more severe depression, more positive symptoms, poorer functional outcome and greater rates of relapse at 1 year than those who stopped and those who had never misused substances. There were no differences in outcome between people who had never misused substances and those who stopped misusing after presentation. CONCLUSIONS: These results support assertive intervention targeted at comorbid substance misuse in individuals with first-episode psychosis.

The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls.

Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n=28) and healthy controls (n=32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebo-controlled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.

Effects of transdermal nicotine on episodic memory in non-smokers with and without schizophrenia.

RATIONALE: Nicotinic agonists may improve attention and memory in humans and may ameliorate some cognitive deficits associated with neuropsychiatric disorders such as schizophrenia. MATERIALS AND METHODS: We investigated the effects of a single dose of nicotine on episodic memory performance in 10 adults with schizophrenia and 12 healthy controls. Participants were nonsmokers in order to avoid confounding effects of nicotine withdrawal and reinstatement on memory. At each of two study visits, participants performed a test of episodic memory before and 4 h after application of a 14-mg transdermal nicotine (or identical placebo) patch in counterbalanced order. RESULTS: Compared with placebo, nicotine treatment was associated with more rapid and accurate recognition of novel items. There was a trend for a treatment by diagnosis interaction, such that the effect of nicotine to reduce false alarms was stronger in the schizophrenia than the control group. There was no effect of nicotine on accuracy or reaction time for identification of previously viewed items. CONCLUSIONS: These data suggest that nicotine improves novelty detection in non-smokers, an effect that may be more pronounced in non-smokers with schizophrenia. Because memory deficits are associated with functional impairment in schizophrenia and because impaired novelty detection has been linked to the positive symptoms of schizophrenia, study of the effects of chronic nicotinic agonist treatment on novelty detection may be warranted.

A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence.

BACKGROUND: Tobacco smoking, driven by the addictive properties of nicotine, is the most prevalent preventable cause of death in the Western world. Accumulated evidence suggests that nicotine may increase appetitive responding for nondrug incentives in the environment. METHODS: To test this hypothesis, we conducted a randomized, double-blind, placebo-controlled, crossover study of the effect of a single dose of transdermal nicotine on reward responsiveness in 30 psychiatrically healthy nonsmokers. A novel signal detection task in which correct responses were differentially rewarded in a 3:1 ratio was used to assess the extent to which participants modulated their behavior as a function of reward. RESULTS: Despite expected adverse effects such as nausea, nicotine significantly increased response bias toward the more frequently rewarded condition, at the expense of accuracy, independent of effects on attention or overall vigilance. Additionally, response bias on placebo was greater in participants who received nicotine in the first session, indicating that an effect of nicotine on reward responsiveness or reward-based learning persisted for at least 1 week. CONCLUSIONS: These findings suggest that a single dose of nicotine enhances response to non-drug-related rewards in the environment, with lasting effects. This effect may contribute to reinforcement of early smoking behavior and development of nicotine dependence.

Predictors of early abstinence in smokers with schizophrenia.

BACKGROUND: In patients with schizophrenia, the smoking cessation rate is low and the burden of smoking-related morbidity and mortality is high. Identification of factors associated with abstinence may allow clinicians to optimize treatment prior to a smoking cessation attempt. METHOD: To identify factors associated with successful smoking cessation in patients with a DSM-IV diagnosis of schizophrenia, we analyzed baseline data from 114 stable outpatient smokers with schizophrenia who participated in 1 of 2 smoking cessation trials. The outcome of interest was 4 weeks' continuous abstinence at the end of a 12-week nicotine dependence treatment intervention. Baseline factors associated with abstinence were identified with univariate methods and entered into a manual, forward-selection multivariable regression model to identify independent predictors of abstinence. The study was conducted from March 1999 to February 2004. RESULTS: Fourteen of 114 participants (12%) had biochemically verified 4 weeks' continuous abstinence at week 12. We included 10 noncorrelated variables with a univariate association with abstinence in a multivariable model, controlling for pharmacotherapy, age, and gender. Age at initiation of smoking and baseline variability in attentiveness, as measured by Continuous Performance Test-AX (CPT-AX) hit reaction time standard error, were independently associated with abstinence. For every year increase in age at initiation of smoking, the OR for abstinence was 1.36 (95% CI = 1.01 to 1.83), p = .048. For every millisecond decrease in the variability of the reaction time of CPT-AX, the OR for achieving abstinence was 1.55 (95% CI = 1.07 to 2.24), p = .021. CONCLUSION: Later initiation of smoking was associated with increased and baseline attentional impairment with reduced odds of abstinence. Additional research to further our understanding of the relationship between attentional impairment and cigarette smoking in schizophrenia may lead to improved nicotine dependence treatments for this group.