Neurocognitive consequences of cigarette smoking in young adults--a comparison with pre-drug performance

The present study examined effects of current and past regular cigarette smoking in young adult subjects. One hundred and twelve 17-21-year-old subjects, assessed since infancy, were evaluated using a battery of neurocognitive tests for which commensurate measures were obtained at 9-12 years of age, prior to the initiation of regular smoking. Smokers, determined by urinalysis and self-report, were categorized as heavy (>9 cigarettes per day) and light (<9 cigarettes per day) current smokers and former smokers, the latter having smoked cigarettes regularly in the past but not for at least 6 months. A third of the subjects were currently smoking cigarettes regularly with half of these being heavy smokers. Among former smokers, the average duration of smoking was slightly less than 2 years. Overall IQ, memory, processing speed, vocabulary, attention and abstract reasoning were the primary outcomes with comparisons being made between each of the three user groups and a control group who never smoked regularly. After accounting for potentially confounding factors including clinical assessment, marihuana use and pre-drug performance in the relevant cognitive domain, current regular smokers did significantly worse than non-smokers in a variety of cognitive areas predicated upon verbal/auditory competence including receptive and expressive vocabulary, oral arithmetic, and auditory memory. This impact of current smoking appears to behave in a dose-response and duration-related fashion. In contrast, former smokers differed from the non-smokers only in the arithmetic task. These results suggest that regular smoking during early adulthood is associated with cognitive impairments in selected domains and that these deficits may be reversed upon cessation. Together, the findings add to the body of evidence to be used in persuading adolescents and young adults against the initiation of smoking and, if currently smoking, the advantages of stopping.     

Neurocognitive performance and clinical changes in olanzapine-treated patients with schizophrenia.

Diffuse cognitive impairment characterizes patients with schizophrenia throughout the course of illness. The deficits persist despite clinical improvement associated with neuroleptic intervention and are related to outcome. It is unclear whether treatment with atypical agents is associated with improved cognition that relates to symptoms and outcome. Using a set of computerized neurocognitive measures, we evaluated whether the effects of olanzapine are greater than practice effects for specific neurocognitive domains that could provide targets for large-scale randomized studies. We enrolled 19 patients with schizophrenia before initiation of treatment with olanzapine and 16 of them were examined at 6 weeks and 6 months of follow-up. They were compared to 34 healthy participants who enrolled, 24 of whom were evaluated longitudinally. Improvement exceeding practice effects was observed in patients for abstraction and spatial memory and the latter correlated with clinical improvement in negative symptoms. These results suggest that some effects of olanzapine may impact both symptoms and cognitive performance.     

Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure

Abuse of the stimulant drug methamphetamine is associated with neural injury and neuropsychological (NP) deficits, while the residual effects of marijuana use remain uncertain. We sought to determine if methamphetamine dependent persons who also met criteria for marijuana abuse or dependence evidenced different NP performance than those with dependence for methamphetamine alone. We examined three groups that did not differ significantly on important demographic factors: (1) subjects with a history of methamphetamine dependence and history of marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a control group with minimal or no drug use (n=41). A comprehensive NP battery was administered and performance was quantified for five cognitive ability areas. The METH+/MJ- group generally demonstrated the greatest NP impairment, with statistically significant differences observed between the METH+/MJ- and control group in learning, retention/retrieval, and a summary score of global NP performance. The METH+/MJ+ group did not differ significantly from the control or METH+/MJ- group on any NP ability. However, there was a significant linear trend in the global NP score suggesting that the METH+/MJ+ performed intermediate to the control and METH+/MJ- groups. Based on these findings, we cannot conclude that there is a protective effect of marijuana use in methamphetamine users; however, marijuana use clearly did not appear to exacerbate methamphetamine neurotoxicity. Further investigations are needed to determine if the emerging literature, suggesting that certain cannabinoids might have neuroprotective actions, is generalizable to community-dwelling substance abusers.     

Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users

Performance impairment during Delta(9)-tetrahydrocannabinol (THC) intoxication has been well described in occasional cannabis users. It is less clear whether tolerance develops to the impairing effects of THC in heavy users of cannabis. The aim of the present study was to assess neurocognitive performance during acute THC intoxication in occasional and heavy users. Twenty-four subjects (12 occasional cannabis users and 12 heavy cannabis users) participated in a double-blind, placebo-controlled, two-way mixed model design. Both groups received single doses of THC placebo and 500 microg/kg THC by smoking. Performance tests were conducted at regular intervals between 0 and 8 h after smoking, and included measures of perceptual motor control (critical tracking task), dual task processing (divided attention task), motor inhibition (stop signal task) and cognition (Tower of London). THC significantly impaired performance of occasional cannabis users on critical tracking, divided attention and the stop signal task. THC did not affect the performance of heavy cannabis users except in the stop signal task, i.e. stop reaction time increased, particularly at high THC concentrations. Group comparisons of overall performance in occasional and heavy users did not reveal any persistent performance differences due to residual THC in heavy users. These data indicate that cannabis use history strongly determines the behavioural response to single doses of THC.     

Neurocognitive effects of alcohol hangover

Alcohol hangover is characterized by adverse physical and mental effects that occur the next morning after the intake of toxic doses of alcohol. One of the more relevant functional consequences of hangover is the cognitive and subjective impairment, which could be related to the high socioeconomic costs of alcohol consumption. Nevertheless, few studies have addressed the study of neurocognitive and subjective effects of hangover. The systematic and exhaustive study of neurocognitive and subjective effects has not been done. In the present work we briefly review the hangover impact, not only in the objective execution of attention, psychomotricity and memory tasks, but in the subjective state of the subjects as well. Moreover, we also highlight the methodology difficulties to study neurocognitive effects of hangover and suggest several aspects to take into account in future investigations.     

Neurocognitive Effects of Nicotine and Tobacco in Individuals with Schizophrenia

ABSTRACT

Schizophrenic patients have deficits in neurocognitive functioning, including attention, verbal learning and memory, executive function, spatial working memory, and pre-attentional measures. Nicotine may enhance these domains of cognitive dysfunction in smokers with schizophrenia, which may be related to the high rates of smoking initiation and maintenance in this population. However, differential effects associated with varying modes of nicotine administration and the accompanying magnitude of these effects of distinct nicotine delivery systems are poorly understood. This article examines the effects of nicotine administration on various aspects of neurocognitive performance in schizophrenia.     

Medicolegal alcohol determination: comparison and consequences of breath and blood analysis

The concentration of alcohol in blood or breath has come to be regarded as the most objective indicator of impaired driving ability for medicolegal and other purposes. Regardless of the analytical method employed, there is substantial uncertainty about impaired driving ability at a particular alcohol concentration because of large differences in response among individuals to a given dose of alcohol. There is additional uncertainty associated with the particular analytical method used. Since breath alcohol analysis is the most common method employed for medicolegal purposes in the U.S., this method is compared to blood alcohol analysis in order to estimate its reliability and explore the numerous consequences resulting from the use of these methods. Results from blood and breath analyses are often used interchangeably, even though they are not necessarily equally valid indicators of impaired driving ability. To satisfy fundamental legal and scientific principles, it is concluded that the total uncertainty involved in a determination of impaired driving ability must be reported or otherwise accounted for in medicolegal applications.     

Neurocognitive deficits are associated with unemployment in chronic methamphetamine users

BACKGROUND: Unemployment rates are high among chronic methamphetamine (MA) users and carry a significant economic burden, yet little is known about the neurocognitive and psychiatric predictors of employment in this vulnerable population. METHODS: The present study examined this issue in 63 participants with recent MA dependence and 47 comparison subjects without histories of MA use disorders. All participants completed a comprehensive neurocognitive, psychiatric and neuromedical evaluation. Individuals with HIV infection, severe neuropsychological or psychiatric conditions that might affect cognition (e.g., seizure disorder, schizophrenia), or a positive Breathalyzer or urine toxicology screen on the day of testing were excluded. RESULTS: Consistent with previous research, a logistic regression revealed MA dependence as a significant, independent predictor of full-time unemployment status. Within the MA-dependent sample, greater impairment in global neurocognitive functioning and history of injection drug use emerged as significant independent predictors of unemployment status. The association between worse global cognitive functioning and unemployment was primarily driven by deficits in executive functions, learning, verbal fluency, and working memory. CONCLUSION: These findings indicate that neurocognitive deficits play a significant role in the higher unemployment rates of MA-dependent individuals, and highlight the need for vocational rehabilitation and supported employment programs that assess and bolster cognitive skills in this population.     

Neurocognitive impairment associated with alcohol use disorders: implications for treatment

Between 50% and 80% of individuals with alcohol use disorders experience mild to severe neurocognitive impairment. There is a strong clinical rationale that neurocognitive impairment is an important source of individual difference affecting many aspects of addiction treatment, but empirical tests of the direct influence of impairment on treatment outcome have yielded weak and inconsistent results. The authors address the schism between applied-theoretical perspectives and research evidence by suggesting alternative conceptual models of the relationship between neurocognitive impairment and addiction treatment outcome. Methods to promote neurocognitive recovery and ways in which addiction treatments may be modified to improve psychosocial adaptation are suggested. Specific suggestions for future research that may help clarify the complex relations between neurocognitive impairment and addiction treatment are outlined.     

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [¹¹C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [¹¹C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [¹¹C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.     

Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions

This review aims to compare cognitive consequence between cannabis, and stimulants and heroin with regards to attention, memory and executive functions. The available studies using brain imaging techniques and neuropsychological tests show that acutely, all drugs create a disharmony in the neuropsychological network, causing a decrease of activity in areas responsible for short-term memory and attention, with the possible exception of heroin. Cannabis induces loss of internal control and cognitive impairment, especially of attention and memory, for the duration of intoxication. Heavy cannabis use is associated with reduced function of the attentional/executive system, as exhibited by decreased mental flexibility, increased perserveration, and reduced learning, to shift and/or sustain attention. Recent investigations on amphetamine/methamphetamine have documented deficits in learning, delayed recall, processing speed, and working memory. MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks. The degree of executive impairment increases with the severity of use, and the impairments are relatively lasting over time. Chronic cocaine users display impaired attention, learning, memory, reaction time and cognitive flexibility. Heroin addiction may have a negative effect on impulse control, and selective processing.     

Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response

Rationale

The N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD). Despite the promise of a novel and urgently needed treatment for refractory depression, concerns regarding potential adverse neurocognitive effects of ketamine remain.

Objectives

Although extensive research has been conducted in healthy volunteers, there is a paucity of studies examining the neurocognitive effects of ketamine in depressed patients. Therefore, the aims of the current study were to characterize the relationship between baseline neurocognition and antidepressant response to ketamine, measure the acute impact of ketamine on neurocognition, and investigate the relationship between acute neurocognitive effects of ketamine and antidepressant response.

Methods

Neurocognitive functioning was assessed in 25 patients with TRD using a comprehensive battery: estimated premorbid intelligence quotient (IQ), current IQ, and tests from the MATRICS Consensus Cognitive Battery (MCCB). A subset of the MCCB was repeated immediately following a 40-min intravenous infusion of ketamine (0.5 mg/kg).

Results

Patients who responded to ketamine 24 h following treatment had poorer baseline neurocognitive performance relative to nonresponders and, in particular, slower processing speed (F?=?8.42; df?=?23; p?=?0.008). Ketamine was associated with selective impairments in memory recall, and the degree of cognitive change carried negative prognostic significance (e.g., negative cognitive effects immediately after ketamine predicted lower response rate at 24 h; Fisher's exact test two-sided p?=?0.027).

Conclusions

Taken together, our findings suggest a potential baseline neurocognitive predictor of ketamine response and an inverse relationship between the cognitive effects of ketamine and antidepressant efficacy.     

Non-cholinergic modulation of antisaccade performance: a modafinil-nicotine comparison

INTRODUCTION: The antisaccade task provides a powerful tool with which to investigate the cognitive and neural systems underlying goal-directed behaviour, particularly in situations when the correct behavioural response requires the suppression of a prepotent response. Antisaccade errors (failures to suppress reflexive prosaccades towards sudden-onset targets) are increased in patients with damage to the dorsolateral prefrontal cortex, and in patients with schizophrenia. Nicotine has been found to improve antisaccade performance in patients with schizophrenia and healthy controls. This performance enhancing effect may be due to direct effects on the cholinergic system, but there has been no test of this hypothesis. MATERIALS AND METHODS: In a double blind, double dummy, placebo-controlled design, we compared the effect of nicotine and modafinil, a putative indirect noradrenergic agonist, on antisaccade performance in healthy non-smokers. RESULTS AND DISCUSSION: Both compounds reduced latency for correct antisaccades, although neither reduced antisaccade errors. These findings are discussed with reference to the pharmacological route of performance enhancement on the antisaccade task and current models of antisaccade performance.     

Effects of amisulpride and aripiprazole on progressive-ratio schedule performance: comparison with clozapine and haloperidol

Clozapine and some other atypical antipsychotics (e.g. quetiapine, olanzapine) have been found to exert a characteristic profile of action on operant behaviour maintained by progressive-ratio schedules, as revealed by Killeen's Mathematical Principles of Reinforcement model of schedule-controlled behaviour. These drugs increase the value of a parameter that expresses the 'incentive value' of the reinforcer (a) and a parameter that is inversely related to the organism's 'motor capacity' (δ). This experiment examined the effects of two further atypical antipsychotics, aripiprazole and amisulpride, on progressive-ratio schedule performance in rats; the effects of clozapine and a conventional antipsychotic, haloperidol, were also examined. In agreement with previous findings, clozapine (4, 8?mg kg(-1)) increased a and δ, whereas haloperidol (0.05, 0.1?mg kg(-1)) reduced a and increased δ. Aripiprazole (3,30?mg kg(-1)) increased δ but did not affect a. Amisulpride (5, 50?mg kg(-1)) had a delayed and protracted effect: δ was increased 3-6 hours after treatment; a was increased 1.5 hours, and reduced 12-24 hours after treatment. Interpretation based on Killeen's model suggests that aripiprazole does not share clozapine's ability to enhance reinforcer value. Amisulpride produced a short-lived enhancement, followed by a long-lasting reduction, of reinforcer value. Both drugs impaired motor performance.