Modafinil, but not escitalopram, improves working memory and sustained attention in long-term, high-dose cocaine users.

OBJECTIVE: The purpose of the present study was to determine the effects of modafinil, escitalopram, and modafinil + escitalopram administration on neurocognition in a sample of long-term, high-dose cocaine users. METHOD: Sixty-one cocaine-dependent individuals were randomly assigned to receive placebo (n = 14), modafinil, 200 mg, once daily (n = 16), escitalopram, 20 mg, once daily (n = 16), or modafinil and escitalopram, once daily (n = 15), for five days on an inpatient basis. Urinanalysis was used to confirm abstinence from cocaine on the day of admission and the next five days. Baseline neurocognitive assessment, which included measures of attention/information processing, episodic memory, and working memory, was conducted immediately after the washout phase and prior to the administration of modafinil. The follow-up assessment was conducted after participants had received modafinil or placebo for five days. RESULTS: Repeated-measures, mixed model analysis of variance showed that modafinil administration was associated with significantly improved performance on two measures of working memory span (mean n-back span, maximum n-back span) and a trend toward significant improvement on a measure of visual working memory (visual accuracy) and two measures of sustained attention, consistency of response time (Variability) and reduced impulsivity (Perseveration). Modafinil administration did not modulate performance on measures of information processing speed or episodic memory. Escitalopram did not modulate performance on measures of cognition, either alone or in combination with modafinil. CONCLUSIONS: This study provides initial data showing that, in a sample of long-term, high-dose cocaine users, administration of psychotropic medications, such as modafinil, can improve performance on measures of working memory. Moreover, it confirms the utility of studying the interactive effects of psychotropic medications to confirm the manner in which the candidate medications independently and interactively affect neurocognition. These effects are likely relevant in the treatment of cocaine dependence, in which the remediation of impaired working memory may be associated with improved treatment outcomes. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

d-Cycloserine administration does not affect neurocognition in concurrent cocaine- and nicotine-dependent volunteers.

Neurocognitive impairment is a well-documented consequence of long-term, repeated cocaine exposure and has been identified as an important target of treatment. Thus, this study sought to determine whether the N-methyl-d-aspartate (NMDA) partial agonist, d-cycloserine could improve neurocognitive performance in a sample of 27 long-term, high dose cocaine dependent individuals who were not seeking treatment at the time of enrollment in the study. This double-blind, placebo-controlled study evaluated whether a single dose of 0 or 50mg of d-cycloserine would enhance performance on measures of attention/information processing speed, episodic memory, and executive/frontal lobe functioning relative to test performance at baseline. The results revealed that d-cycloserine did not modulate neurocognition in this cohort, though there are a number of factors that may have mitigated the effects of d-cycloserine in this particular study. The negative findings notwithstanding, the current study serves as a springboard for future investigations that will examine whether other medications that can modulate neurocognition in cocaine-dependent study participants.

Neurocognitive functioning is associated with employment status: a quantitative review.

Neurocognitive assessment is frequently used as a basis for making determinations regarding a person's ability to work; yet, to our knowledge, a review of the association between neurocognition and employment status has not been conducted. For this review, we utilized meta-analysis to quantify objectively the association between eight neurocognitive domains and employment status. The meta-analysis revealed that performance in each domain was significantly associated with employment status, and that the associations were greatest for the following domains: intellectual functioning, executive functioning, and memory. These findings support the ecological validity of neurocognitive assessment.

Risperidone pre-treatment reduces the euphoric effects of experimentally administered cocaine.

Pre-clinical research implicates dopaminergic neurotransmission as critical in producing the effects of stimulants. Previous stimulant challenge studies using volunteers treated with dopaminergic antagonists have generally failed to demonstrate reduction of subjective effects. We performed this study to determine whether repeated dosing with risperidone reduced the subjective effects of experimentally administered cocaine. Nine non-treatment seeking hospitalized cocaine-dependent volunteers received 40 mg cocaine IV before and following 5 days of treatment with risperidone, 2 mg per day. Risperidone pre-treatment reduced the self-rated 'high' produced by cocaine. Repeated, rather than single, dosing with a D2 antagonist may be necessary to reduce the subjective effects produced by cocaine. The degree of D2 receptor blockade produced by risperidone appears to be greater than the reduction in euphoric effects produced by cocaine, suggesting that mechanisms other than those involving D2 receptors may be important in drug-induced euphoria.

Psychiatric comorbidity of methamphetamine dependence in a forensic sample.

The objective of this study was to examine the association between psychiatric symptoms and methamphetamine dependence. A four-hour survey was administered to 1,580 arrestees sampled from the 14 most populous counties in California. The survey included items assessing demographic profile, history of substance dependence, and psychiatric symptomatology. In the 12 months prior to the assessment, methamphetamine-dependent individuals were more likely to report depressive symptoms and suicidal ideation than individuals denying methamphetamine dependence, even after controlling for demographic profile and dependence on other drugs. Methamphetamine-dependent individuals also were more likely to report a need for psychiatric assistance at the time of the interview. These findings suggest that methamphetamine-dependent individuals are at greater risk to experience particular psychiatric symptoms. Further study to determine the etiology of these symptoms is warranted.

Effects of selegiline pretreatment on response to experimental cocaine administration

Several medications have been reported to alter the subjective effects of experimentally administered cocaine. We studied the effects of selegiline, a monoamine oxidase B inhibitor, on the subjective effects of experimentally administered cocaine in chronically cocaine-dependent subjects. Eight subjects completed a protocol that involved repeated administrations of cocaine before and after treatment with selegiline, given in extended release form, 10 mg per day. Four days of treatment with selegiline was associated with decreased self-reported 'high' and 'stimulated' feelings after cocaine administration, measured as the area under the curve. Changes in other subjective effects were less pronounced. Selegiline pretreatment had minimal effects on the cardiovascular responses to cocaine administration.

Association of depressive symptoms during abstinence with the subjective high produced by cocaine.

OBJECTIVE: During early abstinence, many cocaine-dependent individuals experience symptoms such as anhedonia, craving, fatigue, insomnia, and dysphoria. While several studies have shown an association between depressive symptoms and negative treatment outcome, the reasons for this association are unclear. The authors conducted this study in order to determine the association between severity of depressive symptoms during early abstinence and subjective effects of experimentally administered cocaine. METHOD: Seventeen cocaine-dependent individuals achieved 5 days of abstinence in a hospital setting. Forty mg of cocaine was given intravenously on the fifth day of abstinence, and participants were asked to rate the subjective effects produced by the cocaine. The relationship between the subjective high produced by cocaine and the symptoms experienced during the 5 days of abstinence was evaluated. RESULTS: Individuals experiencing more intense depressive symptoms experienced a significantly greater high from the 40-mg cocaine infusion than individuals who did not. CONCLUSIONS: These data suggest that the severity of depressive symptoms experienced during initial abstinence is associated with the intensity of the subsequent high produced by cocaine. This finding could help explain why individuals who experience greater levels of depression-like symptoms during abstinence appear to be at greater risk for unsuccessful treatment outcome.

How well do standard clinical neuropsychological tests identify malingering? A preliminary analysis.

Neuropsychological research has primarily focused on identification of malingerers through specialized tests designed for this purpose. Little attention has been given to the degree to which traditional clinical measures differentiate between malingerers and non-malingerers. This study examined the neuropsychological performance of 81 subjects who had a history of mild to moderate head injury, some of whom are believed to have been motivated to malinger their test performance. Subjects were classified as malingerers or non-malingerers based on their history as well as their performance on specific neuropsychological malingering tests. Performance on traditional neuropsychological clinical measures was examined for both groups. Results indicated that subjects' pattern of neuropsychological performance was not a reliable indicator of malingering performance, supporting the notion that specialized malingering tests are a critically necessary component to clinical classification of malingering. However, level of performance may provide an indication of malingering, as probable malingerers consistently performed worse on traditional and clinical neuropsychological measures. These findings are discussed in the context of the malingering literature.

Cognitive and behavioral sequelae of closed head injury in older adults according to their significant others.

This study examined the neurobehavioral effects of closed head injury (CHI) in older adults according to their significant others. Informants of 17 mild and moderate CHI patients > or = 50 years old when injured completed the Geriatric Evaluation of Relative's Rating Instrument, a questionnaire inquiring about the patient's cognition, affect, interpersonal relations, and daily activities. The significant others provided retrospective ratings of preinjury functioning and completed the same instrument an average of 4 and 13 months post-injury. The significant others of 10 community-residing, normal control subjects completed the questionnaire at comparable intervals between each rating. Compared with their preinjury functioning, and unlike the control subjects, patients showed declines in cognition and mood. The possible impact of these changes, including their effect on subjective burden in caregivers, is discussed.

Depression predicts procedural but not episodic memory in HIV-1 infection.

Forty-three homosexual/bisexual males with HIV-1 infection participated in a study that sought to determine: (1) whether increased levels of self-reported depressive symptomatology were associated with poorer performance on episodic or procedural memory tasks, (2) the relative strength of association between the affective/cognitive or somatic symptoms of depression and memory deficits and level of immunosuppression, and (3) whether increased depression or neuropsychological deficits are associated with degree of immunosuppression. Linear regression analyses revealed that increased affective/cognitive symptomatology was correlated with poorer performance on a procedural memory task, but was not correlated with performance on an episodic memory task or degree of immunosuppression. In contrast, somatic symptoms showed the strongest association with level of immunosuppression, but were not correlated with performance on the memory tasks. These findings underscore the complex interplay between neuropsychiatric and neuropsychological symptomatology in HIV-1 infection.

Outcomes assessment for forensic neuropsychology: recommendations and considerations.

Neuropsychologists are frequently retained by attorneys or the courts to assist in the resolution of legal disputes. Yet, an outcomes assessment demonstrating the utility of neuropsychological evaluations in the forensic arena has not been implemented, nor has a method for conducting an outcomes assessment of forensic neuropsychology been delineated. This article offers recommendations and considerations for the formulation of outcomes assessments. These include defining an outcomes assessment, identifying the consumers of forensic neuropsychological assessments, and specifying potential moderator and dependent variables in the context of study designs that may be feasibly implemented. Moreover, the ethical implications of outcomes assessments are discussed.

Relationship of IQ to verbal learning and memory: test and retest.

The relationship between Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ and performance on measures of memory was examined in 64 adults tested twice at a 2-week interval. Repeated measures analyses of variance revealed that individuals with Low-Average WAIS-R Full Scale IQ scores performed significantly more poorly than did individuals with Average and High-Average Full Scale IQs on memory measures including the Wechsler Memory Scale-Revised (WMS-R) General Memory and Delayed Recall indices, as well as California Verbal Learning Test (CVLT) Total Words. Learning Slope, and Discriminability. Although all three groups demonstrated significant practice effects on each memory measure, group differences in performance persisted at retest. Multiple regression analyses revealed that WAIS-R factor scores Verbal Comprehension and Freedom from Distractibility accounted for up to 42% of the variance in WMS-R and CVLT indices. Moreover, WAIS-R performance at initial testing accounted for 22-41% of the variance in memory performance at retest. These results are discussed in the context of the construct stabilities of intelligence and memory, as well as the psychometric precision of the tests used to measure these constructs.

Sexually transmitted diseases and acquired immunodeficiency syndrome (AIDS). Changes in risk reduction behaviors among young adults.

Increasing attention has focused on the medical risk to young, unmarried, sexually active adults of contracting sexually transmitted diseases (STDs) in general and acquired immunodeficiency syndrome (AIDS) in particular. Yet little is known empirically about the extent to which this group perceives themselves to be at risk for contracting specific STDs or is changing their behaviors to reduce their risk. In the current study, the authors report findings from two matched samples of unmarried young adults, 182 assessed in the winter of 1986 and 182 in the fall of 1987. Results demonstrated greater worry and concerns about all STDs, including AIDS, in the second sample assessed than in the first. Some behavioral changes also were noted in the second group, including increased use of condoms. Nevertheless, 44% of sexually experienced participants in the fall of 1987 reported that they had not changed their behavior in any way to reduce their risk of acquiring human immunodeficiency virus (HIV) infection.